Molecules

Editorial

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2 pages, 139 KiB

Open AccessEditorial

Remembering Professor Benito Casu (1927–2016)

by Giangiacomo Torri^* and Giuseppe Cassinelli

Carbohydrate Sciences Department of Istituto di Ricerche Chimiche e Biochimiche “G. Ronzoni”, 20133 Milan, Italy

Molecules 2018, 23(2), 292; https://doi.org/10.3390/molecules23020292 - 31 Jan 2018

Cited by 1 | Viewed by 2514

Abstract

Heparin and related drugs have contributed in so many different ways to the drug discovery process, and have provided a platform to understand the pathophysiology of vascular and inflammatory diseases for nearly 100 years. Full article

(This article belongs to the Special Issue Looking Forward to the Future of Heparin: New Sources, Developments and Applications)

4 pages, 154 KiB

Open AccessEditorial

Looking Forward to the Future of Heparin: New Sources, Developments and Applications

by Giangiacomo Torri^* and Giuseppe Cassinelli

Carbohydrate Sciences Department of Istituto di Ricerche Chimiche e Biochimiche “G. Ronzoni”, 20133 Milan, Italy

Molecules 2018, 23(2), 293; https://doi.org/10.3390/molecules23020293 - 31 Jan 2018

Cited by 6 | Viewed by 3398

Abstract

The seven reviews and the eleven articles in this special issue provide an updated survey of recent research and developments in the ever-growing field of heparin, along with low molecular weight heparins (LMWHs) and glycosaminoglycans (GAGs). Full article

(This article belongs to the Special Issue Looking Forward to the Future of Heparin: New Sources, Developments and Applications)

3 pages, 127 KiB

Open AccessEditorial

Advances in Heparins and Related Research. An Epilogue

by Jawed Fareed^*, Peter Bacher and Walter Jeske

Loyola University Medical Center, Maywood, IL 60153, USA

Molecules 2018, 23(2), 390; https://doi.org/10.3390/molecules23020390 - 12 Feb 2018

Cited by 5 | Viewed by 2898

Abstract

The discovery of heparin in 1916 by Jay McLean, a medical student at Johns Hopkins University, not only provided a universal anticoagulant, but also laid the foundation for the discipline of hemostasis and thrombosis[...] Full article

(This article belongs to the Special Issue Looking Forward to the Future of Heparin: New Sources, Developments and Applications)

Research

Jump to: Editorial, Review

13 pages, 2280 KiB

Open AccessArticle

Estrogenic Effects of the Extracts from the Chinese Yam (Dioscorea opposite Thunb.) and Its Effective Compounds in Vitro and in Vivo

by Mengnan Zeng^1,2, Li Zhang^1,2, Miao Li¹, Beibei Zhang^1,2, Ning Zhou¹, Yingying Ke^1,2, Weisheng Feng^1,2,* and Xiaoke Zheng^1,2,*

¹ Department of Medicine, Henan University of Chinese Medicine, China

² Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment & Chinese Medicine Development of Henan Province, China

Molecules 2018, 23(2), 11; https://doi.org/10.3390/molecules23020011 - 23 Jan 2018

Cited by 46 | Viewed by 6216

Abstract

Background: The aim of this study was to explore the estrogenic effects of the extracts from Chinese yam and its effective compounds. Methods: The activity of the yam was investigated by the uterine weight gain of mice and a proliferation assay of breast [...] Read more.

Background: The aim of this study was to explore the estrogenic effects of the extracts from Chinese yam and its effective compounds. Methods: The activity of the yam was investigated by the uterine weight gain of mice and a proliferation assay of breast cancer cell lines (MCF-7 cell); the estrogenic activity was comprehensively evaluated by a serum pharmacology experiment. The levels of estradiol (E2), follicle stimulating hormone (FSH), and luteinizing hormone (LH) were also measured. Western blot analysis and antagonist assays with faslodex (ICI182,780), methylpiperidino-pyrazole (MPP), Delta (9) –tetrahydrocannabinol (THC), and G-15 were used to explore the mechanism of the effects of the yam. To find the effective compounds of the yam which play a role in its estrogen-like effects, we used the same methods to study the effects of adenosine and arbutin. Results: The Chinese yam and two main compounds, adenosine and arbutin, have estrogen-like effects. The mechanism of the yam which plays a role in its estrogen-like effects was mainly mediated by the estrogen receptors ERα, ERβ, and GPR30; that of adenosine was mainly mediated by estrogen receptors ERα and ERβ, and that of arbutin was mainly mediated by estrogen receptors ERβ and GPR30. Conclusions: The Chinese yam has estrogen-like effects; adenosine and arbutin are two of the effective compounds in the yam which play a role in its estrogen-like effects. Full article

(This article belongs to the Collection Bioactive Compounds)

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17 pages, 2844 KiB

Open AccessArticle

Analytical Approaches to Improve Accuracy in Solving the Protein Topology Problem

by Kamal Al Nasr^1,*, Feras Yousef²

, Ruba Jebril¹ and Christopher Jones¹

¹ Department of Computer Science, Tennessee State University, Nashville, TN 37209, USA

² Department of Mathematics, The University of Jordan, Amman 11942, Jordan

Molecules 2018, 23(2), 28; https://doi.org/10.3390/molecules23020028 - 23 Jan 2018

Cited by 7 | Viewed by 4192

Abstract

To take advantage of recent advances in genomics and proteomics it is critical that the three-dimensional physical structure of biological macromolecules be determined. Cryo-Electron Microscopy (cryo-EM) is a promising and improving method for obtaining this data, however resolution is often not sufficient to [...] Read more.

To take advantage of recent advances in genomics and proteomics it is critical that the three-dimensional physical structure of biological macromolecules be determined. Cryo-Electron Microscopy (cryo-EM) is a promising and improving method for obtaining this data, however resolution is often not sufficient to directly determine the atomic scale structure. Despite this, information for secondary structure locations is detectable. De novo modeling is a computational approach to modeling these macromolecular structures based on cryo-EM derived data. During de novo modeling a mapping between detected secondary structures and the underlying amino acid sequence must be identified. DP-TOSS (Dynamic Programming for determining the Topology Of Secondary Structures) is one tool that attempts to automate the creation of this mapping. By treating the correspondence between the detected structures and the structures predicted from sequence data as a constraint graph problem DP-TOSS achieved good accuracy in its original iteration. In this paper, we propose modifications to the scoring methodology of DP-TOSS to improve its accuracy. Three scoring schemes were applied to DP-TOSS and tested: (i) a skeleton-based scoring function; (ii) a geometry-based analytical function; and (iii) a multi-well potential energy-based function. A test of 25 proteins shows that a combination of these schemes can improve the performance of DP-TOSS to solve the topology determination problem for macromolecule proteins. Full article

(This article belongs to the Special Issue Selected Papers from the 10th Computational Structural Bioinformatics Workshop (CSBW-2017))

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12 pages, 4117 KiB

Open AccessArticle

A Facile Route toward the Increase of Oxygen Content in Nanosized Zeolite by Insertion of Cerium and Fluorinated Compounds

by Sarah Komaty¹, Clément Anfray^2,†, Moussa Zaarour^1,†, Hussein Awala¹, Valérie Ruaux¹, Samuel Valable² and Svetlana Mintova^1,*

¹ Laboratoire Catalyse et Spectrochimie, Normandie University, ENSICAEN, UNICAEN, CNRS, 14050 Caen, France

² ISTCT/CERVOxy Group, Normandie University, UNICAEN, CEA, CNRS, 14050 Caen, France

^† Both authors contributed equally to this work.

Molecules 2018, 23(2), 37; https://doi.org/10.3390/molecules23020037 - 24 Jan 2018

Cited by 13 | Viewed by 5596

Abstract

Enriching oxygen content within nanosized zeolite X (as synthesized Na-X) by insertion of cerium (ion exchanged Ce-X) and functionalization with bromoperfluoro-n-octane (fluorinated F-X) is reported. The materials were fully characterized by powder X-ray diffraction (XRD), dynamic light scattering (DLS), zeta potential, [...] Read more.

Enriching oxygen content within nanosized zeolite X (as synthesized Na-X) by insertion of cerium (ion exchanged Ce-X) and functionalization with bromoperfluoro-n-octane (fluorinated F-X) is reported. The materials were fully characterized by powder X-ray diffraction (XRD), dynamic light scattering (DLS), zeta potential, thermogravimetric analysis (TGA), nitrogen adsorption, and nuclear magnetic resonance (¹⁹F NMR). The O₂ adsorption in the zeolite samples at various concentrations (0 to 165 Torr) at −196 °C was studied by in situ FTIR. The modification of nanosized zeolites did not alter their colloidal stability, crystallinity, porosity, and particle size distribution. The inclusion of cerium and bromoperfluoro-n-octane considerably increase the oxygen capacity by 33% for samples Ce-X and F-X in comparison to the as-synthesized Na-X zeolite. Further, toxicity tests revealed that these materials are safe, which opens the door for their implementation in medical applications, where controlled delivery of oxygen is highly desirable. Full article

(This article belongs to the Special Issue Zeolites and Related Nanoporous Materials: Synthesis, Characterization and Applications in Catalysis and Green Chemistry)

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11 pages, 1765 KiB

Open AccessArticle

The Enhanced Intramolecular Energy Transfer and Strengthened ff Luminescence of a Stable Helical Eu Complex in Ionic Liquids

by Yuki Hasegawa¹, Ayumi Ishii^1,2,*, Yudai Inazuka¹, Naho Yajima¹, Shogo Kawaguchi³, Kunihisa Sugimoto³

and Miki Hasegawa^1,*

¹ Department of Chemistry and Biological Science, College of Science and Engineering, Aoyama Gakuin University, 5-10-1 Fuchinobe, Chuo-ku, Sagamihara 252-5258, Kanagawa, Japan

² JST, PRESTO, 4-1-8 Honcho, Kawaguchi 332-0012, Saitama, Japan

³ Research & Utilization Division, Japan Synchrotron Radiation Research Institute (JASRI/SPring-8), 1-1-1 Kouto, Sayo 679-5198, Hyogo, Japan

Molecules 2018, 23(2), 55; https://doi.org/10.3390/molecules23020055 - 24 Jan 2018

Cited by 11 | Viewed by 4986

Abstract

The luminescence of a Eu complex (EuL) is enhanced by stabilization of the coordination structure in highly viscous ionic liquids. The EuL was found to maintain a stable single helical structure both in organic solvents and in the ionic liquids [BMIM][PF₆] [...] Read more.

The luminescence of a Eu complex (EuL) is enhanced by stabilization of the coordination structure in highly viscous ionic liquids. The EuL was found to maintain a stable single helical structure both in organic solvents and in the ionic liquids [BMIM][PF₆] and [EMIM][PF₆]. A colorless solution of EuL dissolved in [BMIM][PF₆] exhibits bright red luminescence with a quantum yield of 32.3%, a value that is much higher than that in acetonitrile (12%). Estimated rate constants for the energy relaxation pathway indicate that the energy transfer efficiency is enhanced in [BMIM][PF₆] as a result of the suppression of molecular fluctuations in the ligands. Additionally, a highly luminescent helical structure is preserved in [EMIM][PF₆] up to 120 °C. Full article

(This article belongs to the Special Issue Lanthanide Luminescence: Fundamental Research and Applications)

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23 pages, 3663 KiB

Open AccessArticle

Indole-3-Carbonitriles as DYRK1A Inhibitors by Fragment-Based Drug Design

by Rosanna Meine^1,2, Walter Becker³, Hannes Falke¹, Lutz Preu¹, Nadège Loaëc⁴, Laurent Meijer⁴

and Conrad Kunick^1,2,*

¹ Institut für Medizinische und Pharmazeutische Chemie, Technische Universität Braunschweig, Beethovenstraße 55, 38106 Braunschweig, Germany

² Zentrum für Pharmaverfahrenstechnik (PVZ), Technische Universität Braunschweig, Franz-Liszt-Straße 35A, 38106 Braunschweig, Germany

³ Institute of Pharmacology and Toxicology, Medical Faculty of the RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany

⁴ ManRos Therapeutics, Perharidy Research Center, 29680 Roscoff, France

Molecules 2018, 23(2), 64; https://doi.org/10.3390/molecules23020064 - 24 Jan 2018

Cited by 24 | Viewed by 6931

Abstract

Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a potential drug target because of its role in the development of Down syndrome and Alzheimer’s disease. The selective DYRK1A inhibitor 10-iodo-11H-indolo[3,2-c]quinoline-6-carboxylic acid (KuFal194), a large, flat and lipophilic molecule, suffers from [...] Read more.

Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a potential drug target because of its role in the development of Down syndrome and Alzheimer’s disease. The selective DYRK1A inhibitor 10-iodo-11H-indolo[3,2-c]quinoline-6-carboxylic acid (KuFal194), a large, flat and lipophilic molecule, suffers from poor water solubility, limiting its use as chemical probe in cellular assays and animal models. Based on the structure of KuFal194, 7-chloro-1H-indole-3-carbonitrile was selected as fragment template for the development of smaller and less lipophilic DYRK1A inhibitors. By modification of this fragment, a series of indole-3-carbonitriles was designed and evaluated as potential DYRK1A ligands by molecular docking studies. Synthesis and in vitro assays on DYRK1A and related protein kinases identified novel double-digit nanomolar inhibitors with submicromolar activity in cell culture assays. Full article

(This article belongs to the Section Medicinal Chemistry)

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18 pages, 1805 KiB

Open AccessArticle

Metabolite Profiling of 14 Wuyi Rock Tea Cultivars Using UPLC-QTOF MS and UPLC-QqQ MS Combined with Chemometrics

by Si Chen^1,2

, Meihong Li^1,2, Gongyu Zheng¹, Tingting Wang¹, Jun Lin², Shanshan Wang², Xiaxia Wang², Qianlin Chao³, Shixian Cao³, Zhenbiao Yang^1,2,4 and Xiaomin Yu^1,2,*

¹ College of Horticulture, Fujian Agriculture and Forestry University, Fuzhou 350002, China

² FAFU-UCR Joint Center for Horticultural Biology and Metabolomics, Fujian Provincial Key Laboratory of Haixia Applied Plant Systems Biology, Fujian Agriculture and Forestry University, Fuzhou 350002, China

³ Wuyi Star Tea Industry Co., Ltd., Wuyishan 354300, China

⁴ Center for Plant Cell Biology, Institute of integrated Genome Biology, and Department of Botany and Plant Sciences, University of California, Riverside, CA 92521, USA

Molecules 2018, 23(2), 104; https://doi.org/10.3390/molecules23020104 - 24 Jan 2018

Cited by 100 | Viewed by 9687

Abstract

Wuyi Rock tea, well-recognized for rich flavor and long-lasting fragrance, is a premium subcategory of oolong tea mainly produced in Wuyi Mountain and nearby regions of China. The quality of tea is mainly determined by the chemical constituents in the tea leaves. However, [...] Read more.

Wuyi Rock tea, well-recognized for rich flavor and long-lasting fragrance, is a premium subcategory of oolong tea mainly produced in Wuyi Mountain and nearby regions of China. The quality of tea is mainly determined by the chemical constituents in the tea leaves. However, this remains underexplored for Wuyi Rock tea cultivars. In this study, we investigated the leaf metabolite profiles of 14 major Wuyi Rock tea cultivars grown in the same producing region using UPLC-QTOF MS and UPLC-QqQ MS with data processing via principal component analysis and cluster analysis. Relative quantitation of 49 major metabolites including flavan-3-ols, proanthocyanidins, flavonol glycosides, flavone glycosides, flavonone glycosides, phenolic acid derivatives, hydrolysable tannins, alkaloids and amino acids revealed clear variations between tea cultivars. In particular, catechins, kaempferol and quercetin derivatives were key metabolites responsible for cultivar discrimination. Information on the varietal differences in the levels of bioactive/functional metabolites, such as methylated catechins, flavonol glycosides and theanine, offers valuable insights to further explore the nutritional values and sensory qualities of Wuyi Rock tea. It also provides potential markers for tea plant fingerprinting and cultivar identification. Full article

(This article belongs to the Special Issue Innovative Extraction Techniques and Hyphenated Instrument Configuration for Complex Matrices Analysis)

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12 pages, 1287 KiB

Open AccessArticle

Use of an UHPLC-MS/MS Method for Determination of Kuraridin and Characterization of Its Metabolites in Rat Plasma after Oral Administration

by Yi Liu¹

, Lei Chen², Wei Cai³, Lin-lin Zhao² and Zhi-xian Mo^1,*

¹ School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China

² Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of TCM, China; Engineering & Technology Research Center for Chinese Materia Medical Quality of the Universities of Guangdong Province, Guangdong Pharmaceutical University, Guangzhou 510006, China

³ Department of Pharmacy, Hunan University of Medicine, Huaihua 418000, China

Molecules 2018, 23(2), 132; https://doi.org/10.3390/molecules23020132 - 24 Jan 2018

Cited by 9 | Viewed by 3833

Abstract

Kuraridin is an active natural prenylated flavonoid ingredient originating from the well-known traditional Chinese medicine Sophora flavescens Ait., that possesses various bioactivities, such as antitumor activity, PLC_γ1 inhibitory activity, glycosidase inhibitory activity, etc. However, there is no report on the plasma [...] Read more.

Kuraridin is an active natural prenylated flavonoid ingredient originating from the well-known traditional Chinese medicine Sophora flavescens Ait., that possesses various bioactivities, such as antitumor activity, PLC_γ1 inhibitory activity, glycosidase inhibitory activity, etc. However, there is no report on the plasma metabolic profile and pharmacokinetic study of kuraridin. The current study was designed to use an ultra-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) method for the quantification and characterization metabolites in rat plasma after oral administration of kuraridin. A liquid-liquid extraction method with ethyl acetate-acetonitrile (1:3) was used to extract the kuraridin from rat plasma samples. The chromatographic separation was carried out on a Hypersil GOLD UHPLC C18 column equipped with a C18 guard cartridge using a gradient elution with organic solvent-water as mobile phase. Based on comparing the retention times with reference standards or on the basis of MS₂ fragmentation behaviors, a total of 19 metabolites were identified or tentatively characterized from rat plasma. Under the optimized conditions, the method showed good linearity (r² > 0.99) over the ranges of 1–500 ng/mL for kuraridin. The inter- and intra-day precisions were less than 8.95%, and the accuracy was in the range of −6.27–6.48%. The recovery of kuraridin ranged from 90.1% to 100.4%. The developed UHPLC-MS/MS method was thus successfully applied in the qualitative of metabolites and quantitative analysis of kuraridin in rat plasma. Full article

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10 pages, 522 KiB

Open AccessArticle

Proteomic Analysis of Differentially-Expressed Proteins in the Liver of Streptozotocin-Induced Diabetic Rats Treated with Parkia biglobosa Protein Isolate

by Bolajoko Idiat Ogunyinka¹, Babatunji Emmanuel Oyinloye^1,2

, Foluso Oluwagbemiga Osunsanmi¹, Andrew Rowland Opoku¹ and Abidemi Paul Kappo^1,*

¹ Biotechnology and Structural Biology (BSB) Group, Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3886, South Africa

² Department of Biochemistry, College of Sciences, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria

Molecules 2018, 23(2), 156; https://doi.org/10.3390/molecules23020156 - 24 Jan 2018

Cited by 4 | Viewed by 4011

Abstract

Protein isolate from Parkia biglobosa seeds is believed to possess excellent anti-diabetic properties. The purpose of this study was to identify differentially expressed proteins in liver of streptozotocin-induced diabetic rats treated with Parkia biglobosa seeds protein isolate (PBPi). In this study, total proteins [...] Read more.

Protein isolate from Parkia biglobosa seeds is believed to possess excellent anti-diabetic properties. The purpose of this study was to identify differentially expressed proteins in liver of streptozotocin-induced diabetic rats treated with Parkia biglobosa seeds protein isolate (PBPi). In this study, total proteins extracted from rat liver were separated on one-dimensional SDS polyacrylamide gel (1D SDS-PAGE) and stained with Coomassie brilliant blue (CBB) to visualize protein bands. We observed that protein bands in the region of 10–15 kDa were altered by the different treatments; these bands were selected and excised for in-gel digestion and peptide extraction followed by nLC-MS, MALDI-TOF MS, and LIFT MS/MS. A database search with the Mascot algorithm positively identified four differentially expressed proteins. These proteins are known to be responsible for diverse biological functions within various organs and tissues. The present result gives insight and understanding into possible molecular mechanisms by which streptozotocin causes various alterations in proteins found in the liver of diabetic rats and the possible modulatory role of PBPi in the management of streptozotocin-induced diabetes. Full article

(This article belongs to the Special Issue Medicinal Plants and Diabetes)

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13 pages, 2820 KiB

Open AccessArticle

Antioxidant and Cytoprotective Effects of Tibetan Tea and Its Phenolic Components

by Hong Xie^1,2,†, Xican Li^1,2,*,†

, Zhenxing Ren^3,4, Weimin Qiu¹, Jianlan Chen¹, Qian Jiang^1,2, Ban Chen^1,2 and Dongfeng Chen^3,4,*

¹ School of Chinese Herbal Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

² Innovative Research & Development Laboratory of TCM, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Guangzhou 510006, China

³ School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

⁴ The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 179; https://doi.org/10.3390/molecules23020179 - 24 Jan 2018

Cited by 50 | Viewed by 5808

Abstract

Tibetan tea (Kangzhuan) is an essential beverage of the Tibetan people. In this study, a lyophilized aqueous extract of Tibetan tea (LATT) was prepared and analyzed by HPLC. The results suggested that there were at least five phenolic components, including gallic [...] Read more.

Tibetan tea (Kangzhuan) is an essential beverage of the Tibetan people. In this study, a lyophilized aqueous extract of Tibetan tea (LATT) was prepared and analyzed by HPLC. The results suggested that there were at least five phenolic components, including gallic acid, and four catechins (i.e., (+)-catechin, (−)-catechin gallate (CG), (−)-epicatechin gallate (ECG), and (−)-epigallocatechin gallate). Gallic acid, the four catechins, and LATT were then comparatively investigated by four antioxidant assays: ferric reducing antioxidant power, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO•) scavenging, 1,1-diphenyl-2-picryl-hydrazl radical scavenging, and 2,2′-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) radical scavenging assays. In these assays, LATT, along with the five phenolic components, increased their antioxidant effects in a concentration-dependent manner; however, the half maximal scavenging concentrations of ECG were always lower than those of CG. Gallic acid and the four catechins were also suggested to chelate Fe²⁺ based on UV-visible spectral analysis. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC−ESI−Q−TOF−MS/MS) analysis suggested that, when mixed with PTIO•, the five phenolic components could yield two types of radical adduct formation (RAF) products (i.e., tea phenolic dimers and tea phenolic-PTIO• adducts). In a flow cytometry assay, (+)-catechin and LATT was observed to have a cytoprotective effect towards oxidative-stressed bone marrow-derived mesenchymal stem cells. Based on this evidence, we concluded that LATT possesses antioxidative or cytoprotective properties. These effects may mainly be attributed to the presence of phenolic components, including gallic acid and the four catechins. These phenolic components may undergo electron transfer, H⁺-transfer, and Fe²⁺-chelating pathways to exhibit antioxidative or cytoprotective effects. In these effects, two diastereoisomeric CG and ECG showed differences to which a steric effect from the 2-carbon may contribute. Phenolic component decay may cause RAF in the antioxidant process. Full article

(This article belongs to the Special Issue Catechin in Human Health and Disease)

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15 pages, 704 KiB

Open AccessArticle

The Integrative Method Based on the Module-Network for Identifying Driver Genes in Cancer Subtypes

by Xinguo Lu^1,*

, Xing Li¹, Ping Liu², Xin Qian¹

, Qiumai Miao¹ and Shaoliang Peng^1,3,*

¹ College of Computer Science and Electronic Engineering, Hunan University, Changsha 410082, China

² Hunan Want Want Hospital, Changsha 410006, China

³ School of Computer Science, National University of Defense Technology, Changsha 410073, China

Molecules 2018, 23(2), 183; https://doi.org/10.3390/molecules23020183 - 24 Jan 2018

Cited by 26 | Viewed by 5508

Abstract

With advances in next-generation sequencing(NGS) technologies, a large number of multiple types of high-throughput genomics data are available. A great challenge in exploring cancer progression is to identify the driver genes from the variant genes by analyzing and integrating multi-types genomics data. Breast [...] Read more.

With advances in next-generation sequencing(NGS) technologies, a large number of multiple types of high-throughput genomics data are available. A great challenge in exploring cancer progression is to identify the driver genes from the variant genes by analyzing and integrating multi-types genomics data. Breast cancer is known as a heterogeneous disease. The identification of subtype-specific driver genes is critical to guide the diagnosis, assessment of prognosis and treatment of breast cancer. We developed an integrated frame based on gene expression profiles and copy number variation (CNV) data to identify breast cancer subtype-specific driver genes. In this frame, we employed statistical machine-learning method to select gene subsets and utilized an module-network analysis method to identify potential candidate driver genes. The final subtype-specific driver genes were acquired by paired-wise comparison in subtypes. To validate specificity of the driver genes, the gene expression data of these genes were applied to classify the patient samples with 10-fold cross validation and the enrichment analysis were also conducted on the identified driver genes. The experimental results show that the proposed integrative method can identify the potential driver genes and the classifier with these genes acquired better performance than with genes identified by other methods. Full article

(This article belongs to the Special Issue Selected Papers from the Second CCF Bioinformatics Conference (CBC 2017))

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12 pages, 1209 KiB

Open AccessArticle

Jasmonate-Elicited Stress Induces Metabolic Change in the Leaves of Leucaena leucocephala

by Yingchao Xu^1,2, Zhenru Tao^1,2, Yu Jin^1,2, Shuangyan Chen^1,3, Zhongyu Zhou^1,4,*, Amy G. W. Gong⁴, Yunfei Yuan¹, Tina T. X. Dong⁴ and Karl W. K. Tsim⁴

¹ Key Laboratory of Plant Resources Conservation and Sustainable Utilization, Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, China

² University of Chinese Academy of Sciences, Beijing 100049, China

³ College of Light Industry and Food Sciences, Zhongkai University of Agriculture and Engineering, Guangzhou 510225, China

⁴ Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Hong Kong, China

Molecules 2018, 23(2), 188; https://doi.org/10.3390/molecules23020188 - 24 Jan 2018

Cited by 8 | Viewed by 3690

Abstract

The plant Leucaena leucocephala was exposed to four jasmonate elicitors, i.e., jasmonic acid (JA), methyl jasmonic acid (MeJA), jasmonoyl-l-isoleucine (JA-Ile) and 6-ethyl indanoyl glycine conjugate (2-[(6-ethyl-1-oxo-indane-4-carbonyl)-amino]-acetic acid methyl ester) (CGM). The treatment was to mimic the herbivores and wounding stresses. By [...] Read more.

The plant Leucaena leucocephala was exposed to four jasmonate elicitors, i.e., jasmonic acid (JA), methyl jasmonic acid (MeJA), jasmonoyl-l-isoleucine (JA-Ile) and 6-ethyl indanoyl glycine conjugate (2-[(6-ethyl-1-oxo-indane-4-carbonyl)-amino]-acetic acid methyl ester) (CGM). The treatment was to mimic the herbivores and wounding stresses. By using NMR spectroscopy along with chemometric analysis, including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), the changes of metabolites in the leaves of L. leucocephala were determined under the stress as induced by the four elicitors. The challenge of JA-Ile caused an accumulation of lactic acid (6), β-glucose (10), alanine (12), threonine (13), steroids (18), 3,4-dihydroxypyridine (19) and an unidentified compound 20. The chemometric analysis of the PCA and PLS-DA models indicated that the alternation of metabolites triggered by JA, MeJA, and CGM treatments were very minimum. In contrast, the treatment by JA-Ile could induce the most significant metabolic changes in the leaves. Moreover, there was very minimal new metabolite being detected in responding to the jasmonate-induced stresses. The results showed some metabolite concentrations changed after application of the elicitors, which may be related to a high level of tolerance to stress conditions as well as the strong ecological suitability of L. leucocephala. Full article

(This article belongs to the Section Metabolites)

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18 pages, 5852 KiB

Open AccessArticle

Genome-Wide Identification and Comparative Analysis of the 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase (HMGR) Gene Family in Gossypium

by Wei Liu^1,†, Zhiqiang Zhang^1,†, Wei Li^2,†, Wei Zhu¹, Zhongying Ren², Zhenyu Wang², Lingli Li¹, Lin Jia¹, Shuijin Zhu^3,* and Zongbin Ma^1,*

¹ Collaborative Innovation Center of Henan Grain Crops/Agronomy College, Henan Agricultural University, Zhengzhou 450002, China

² State Key Laboratory of Cotton Biology/Institute of Cotton Research of Chinese Academy of Agricultural Sciences, Anyang 455000, China

³ Department of Agronomy, Zhejiang University, Hangzhou 310058, China

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 193; https://doi.org/10.3390/molecules23020193 - 24 Jan 2018

Cited by 20 | Viewed by 4949

Abstract

Terpenes are the largest and most diverse class of secondary metabolites in plants and play a very important role in plant adaptation to environment. 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is a rate-limiting enzyme in the process of terpene biosynthesis in the cytosol. Previous [...] Read more.

Terpenes are the largest and most diverse class of secondary metabolites in plants and play a very important role in plant adaptation to environment. 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is a rate-limiting enzyme in the process of terpene biosynthesis in the cytosol. Previous study found the HMGR genes underwent gene expansion in Gossypium raimondii, but the characteristics and evolution of the HMGR gene family in Gossypium genus are unclear. In this study, genome-wide identification and comparative study of HMGR gene family were carried out in three Gossypium species with genome sequences, i.e., G. raimondii, Gossypium arboreum, and Gossypium hirsutum. In total, nine, nine and 18 HMGR genes were identified in G. raimondii, G. arboreum, and G. hirsutum, respectively. The results indicated that the HMGR genes underwent gene expansion and a unique gene cluster containing four HMGR genes was found in all the three Gossypium species. The phylogenetic analysis suggested that the expansion of HMGR genes had occurred in their common ancestor. There was a pseudogene that had a 10-bp deletion resulting in a frameshift mutation and could not be translated into functional proteins in G. arboreum and the A-subgenome of G. hirsutum. The expression profiles of the two pseudogenes showed that they had tissue-specific expression. Additionally, the expression pattern of the pseudogene in the A-subgenome of G. hirsutum was similar to its paralogous gene in the D-subgenome of G. hirsutum. Our results provide useful information for understanding cytosolic terpene biosynthesis in Gossypium species. Full article

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13 pages, 2624 KiB

Open AccessArticle

Quercetin Suppresses CYR61-Mediated Multidrug Resistance in Human Gastric Adenocarcinoma AGS Cells

by Ho Bong Hyun¹, Jeong Yong Moon² and Somi Kim Cho^1,2,3,*

¹ Faculty of Biotechnology, College of Applied Life Sciences, SARI, Jeju National University, Jeju 63243, Korea

² Subtropical/Tropical Organism Gene Bank, Jeju National University, Jeju 63243, Korea

³ Faculty of Advanced Convergence Technology & Science, Jeju National University, Jeju 63243, Korea

Molecules 2018, 23(2), 209; https://doi.org/10.3390/molecules23020209 - 24 Jan 2018

Cited by 34 | Viewed by 5359

Abstract

Cysteine-rich angiogenic inducer 61 (CYR61) is an extracellular matrix-associated protein involved in survival, tumorigenesis, and drug resistance. Therefore, we examined the effects of flavones against CYR61-overexpressing human gastric adenocarcinoma AGS (AGS-cyr61) cells, which show remarkable resistance to 5-fluorouracil (5-FU), adriamycin (ADR), tamoxifen (TAM), [...] Read more.

Cysteine-rich angiogenic inducer 61 (CYR61) is an extracellular matrix-associated protein involved in survival, tumorigenesis, and drug resistance. Therefore, we examined the effects of flavones against CYR61-overexpressing human gastric adenocarcinoma AGS (AGS-cyr61) cells, which show remarkable resistance to 5-fluorouracil (5-FU), adriamycin (ADR), tamoxifen (TAM), paclitaxel (PAC), and docetaxel (DOC). Among the tested flavones, quercetin had the lowest 50% inhibitory concentration (IC₅₀) and significantly reduced the viability of AGS-cyr61 cells compared with AGS cells. Quercetin: (1) reduced multidrug resistance-associated protein 1 and nuclear factor (NF)-kappa B p65 subunit levels; (2) reversed multidrug resistance (MDR); (3) inhibited colony formation and induced caspase-dependent apoptosis; and (4) suppressed migration and down-regulated epithelial–mesenchymal transition-related proteins in AGS-cyr61. Moreover, AGS-cyr61 cells treated with quercetin concentrations close to the IC₅₀ and simultaneously treated with 5-FU or ADR in the sub-lethal range showed strong synergism between quercetin and these two drugs. These findings indicate that CYR61 is a potential regulator of drug resistance and that quercetin may be a novel agent for improving the efficacy of anticancer drugs in AGS-cyr61 cells. Full article

(This article belongs to the Collection Herbal Medicine Research)

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22 pages, 4263 KiB

Open AccessArticle

Informing Efforts to Develop Nitroreductase for Amine Production

by Anne-Frances Miller^1,*, Jonathan T. Park², Kyle L. Ferguson^3,†, Warintra Pitsawong^4,‡ and Andreas S. Bommarius^5,*

¹ Department of Chemistry, University of Kentucky, Lexington, KY 40506-0055, USA

² School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0100, USA

³ School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0100, USA

⁴ Department of Chemistry, University of Kentucky, Lexington, KY 40506-0055, USA

⁵ School of Chemical and Biomolecular Engineering, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0100, USA

^† Present address: Department of Chemistry, University of Michigan, Ann Arbor, MI 48104, USA.

^‡ Present address: Department Biochemistry, Brandeis University, Waltham, MA 02453, USA.

Molecules 2018, 23(2), 211; https://doi.org/10.3390/molecules23020211 - 24 Jan 2018

Cited by 32 | Viewed by 7836

Abstract

Nitroreductases (NRs) hold promise for converting nitroaromatics to aromatic amines. Nitroaromatic reduction rate increases with Hammett substituent constant for NRs from two different subgroups, confirming substrate identity as a key determinant of reactivity. Amine yields were low, but compounds yielding amines tend to [...] Read more.

Nitroreductases (NRs) hold promise for converting nitroaromatics to aromatic amines. Nitroaromatic reduction rate increases with Hammett substituent constant for NRs from two different subgroups, confirming substrate identity as a key determinant of reactivity. Amine yields were low, but compounds yielding amines tend to have a large π system and electron withdrawing substituents. Therefore, we also assessed the prospects of varying the enzyme. Several different subgroups of NRs include members able to produce aromatic amines. Comparison of four NR subgroups shows that they provide contrasting substrate binding cavities with distinct constraints on substrate position relative to the flavin. The unique architecture of the NR dimer produces an enormous contact area which we propose provides the stabilization needed to offset the costs of insertion of the active sites between the monomers. Thus, we propose that the functional diversity included in the NR superfamily stems from the chemical versatility of the flavin cofactor in conjunction with a structure that permits tremendous active site variability. These complementary properties make NRs exceptionally promising enzymes for development for biocatalysis in prodrug activation and conversion of nitroaromatics to valuable aromatic amines. We provide a framework for identifying NRs and substrates with the greatest potential to advance. Full article

(This article belongs to the Special Issue Flavoenzymes)

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12 pages, 1200 KiB

Open AccessArticle

Synthesis and Optical Properties of Near-Infrared meso-Phenyl-Substituted Symmetric Heptamethine Cyanine Dyes

by Andrew Levitz^1,†

, Fahad Marmarchi^1,† and Maged Henary^1,2,*

¹ Department of Chemistry, Georgia State University, 50 Decatur St., Atlanta, GA 30303, USA

² Center for Diagnostics and Therapeutics, Georgia State University, Petit Science Center, 100 Piedmont Ave SE, Atlanta, GA 30303, USA

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 226; https://doi.org/10.3390/molecules23020226 - 24 Jan 2018

Cited by 29 | Viewed by 7895

Abstract

Heptamethine cyanine dyes are a class of near infrared fluorescence (NIRF) probes of great interest in bioanalytical and imaging applications due to their modifiability, allowing them to be tailored for particular applications. Generally, modifications at the meso-position of these dyes are achieved [...] Read more.

Heptamethine cyanine dyes are a class of near infrared fluorescence (NIRF) probes of great interest in bioanalytical and imaging applications due to their modifiability, allowing them to be tailored for particular applications. Generally, modifications at the meso-position of these dyes are achieved through Suzuki-Miyaura C-C coupling and S_RN1 nucleophilic substitution of the chlorine atom at the meso-position of the dye. Herein, a series of 15 meso phenyl-substituted heptamethine cyanines was synthesized utilizing a modified dianil linker. Their optical properties, including molar absorptivity, fluorescence, Stokes shift, and quantum yield were measured. The HSA binding affinities of two representative compounds were measured and compared to that of a series of trimethine cyanines previously synthesized by our lab. The results indicate that the binding of these compounds to HSA is not only dependent on hydrophobicity, but may also be dependent on steric interferences in the binding site and structural dynamics of the NIRF compounds. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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15 pages, 10134 KiB

Open AccessFeature PaperArticle

Accurate Estimation of the Standard Binding Free Energy of Netropsin with DNA

by Hong Zhang¹, Hugo Gattuso^2,3, Elise Dumont⁴, Wensheng Cai^1,5

, Antonio Monari^2,3, Christophe Chipot^2,3,6,7 and François Dehez^2,3,6,*

¹ Research Center for Analytical Sciences, College of Chemistry, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Nankai University, Tianjin 300071, China

² UMR 7019, Theoretical Physics and Chemistry Department (LPCT), Université de Lorraine-Nancy, 54506 Vandoeuvre-lès-Nancy, France

³ UMR 7019, Theoretical Physics and Chemistry Department (LPCT), CNRS, 54506 Vandeouvre-lès-Nancy, France

⁴ Univ Lyon, Ens de Lyon, CNRS UMR 5182, Laboratoire de Chimie, Université Claude Bernard Lyon 1, F-69342 Lyon, France

⁵ Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin 300071, China

⁶ Laboratoire International Associé Centre National de la Recherche Scientifique et University of Illinois at Urbana-Champaign, Champaign, Illinois, 54506 Vandeouvre-lès-Nancy, France

⁷ Department of Physics, University of Illinois at Urbana-Champaign, 1110 West Green Street, Urbana, IL 61801, USA

Molecules 2018, 23(2), 228; https://doi.org/10.3390/molecules23020228 - 25 Jan 2018

Cited by 38 | Viewed by 6363

Abstract

DNA is the target of chemical compounds (drugs, pollutants, photosensitizers, etc.), which bind through non-covalent interactions. Depending on their structure and their chemical properties, DNA binders can associate to the minor or to the major groove of double-stranded DNA. They can also intercalate [...] Read more.

DNA is the target of chemical compounds (drugs, pollutants, photosensitizers, etc.), which bind through non-covalent interactions. Depending on their structure and their chemical properties, DNA binders can associate to the minor or to the major groove of double-stranded DNA. They can also intercalate between two adjacent base pairs, or even replace one or two base pairs within the DNA double helix. The subsequent biological effects are strongly dependent on the architecture of the binding motif. Discriminating between the different binding patterns is of paramount importance to predict and rationalize the effect of a given compound on DNA. The structural characterization of DNA complexes remains, however, cumbersome at the experimental level. In this contribution, we employed all-atom molecular dynamics simulations to determine the standard binding free energy of DNA with netropsin, a well-characterized antiviral and antimicrobial drug, which associates to the minor groove of double-stranded DNA. To overcome the sampling limitations of classical molecular dynamics simulations, which cannot capture the large change in configurational entropy that accompanies binding, we resort to a series of potentials of mean force calculations involving a set of geometrical restraints acting on collective variables. Full article

(This article belongs to the Special Issue Frontiers in Computational Chemistry for Drug Discovery)

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11 pages, 1893 KiB

Open AccessFeature PaperArticle

Nano/Mesoporous Carbon from Rice Starch for Voltammetric Detection of Ascorbic Acid

by Mohammad A. Wahab^1,*,†, Farzana Darain^2,3,†, Nazrul Islam⁴ and David James Young^1,*

¹ Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Maroochydore DC, QLD 4558, Australia

² Australian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland, St Lucia, QLD 4072, Australia

³ Sugar Research Australia Ltd., Indooroopilly, QLD 4068, Australia

⁴ Pharmacy Discipline, Faculty of Health, School of Clinical Sciences, QUT, 2 George Street, Brisbane, QLD 4000, Australia

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 234; https://doi.org/10.3390/molecules23020234 - 25 Jan 2018

Cited by 6 | Viewed by 5582

Abstract

Rice starch (RS-)based nano/mesoporous carbon (RSNMC) was prepared via a hard-templating route using cheap rice starch as a carbon source. XRD and TEM characterization indicated the formation of organized nanoporous RSNMC. Nitrogen absorption–desorption studies revealed a high surface area of up to 488 [...] Read more.

Rice starch (RS-)based nano/mesoporous carbon (RSNMC) was prepared via a hard-templating route using cheap rice starch as a carbon source. XRD and TEM characterization indicated the formation of organized nanoporous RSNMC. Nitrogen absorption–desorption studies revealed a high surface area of up to 488 m²∙g⁻¹, uniform pore size of 3.92 nm, and pore volume of 1.14 cm³∙g⁻¹. A RSNMC-modified glassy carbon (GC) electrode was employed for the determination of ascorbic acid (AA) and exhibited a linear response in the concentration range of 0.005–6.0 mM with a detection limit of 0.003 mM. These results demonstrate that RSNMC has potential as an advanced and cheap electrode material for electrochemical sensing and other electrocatalytic applications. Full article

(This article belongs to the Special Issue Functional Molecular Materials)

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12 pages, 2831 KiB

Open AccessArticle

Immunomodulatory Effect of Tremella Polysaccharides against Cyclophosphamide-Induced Immunosuppression in Mice

by Yalin Zhou^{1,2,3,4,*,†}, Xiaoyong Chen^1,2,3,4,†, Ruokun Yi^1,2,3,4, Guijie Li^1,2,3,4, Peng Sun^1,2,3,4, Yu Qian^1,2,3,4 and Xin Zhao^1,2,3,4,*

¹ Department of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, China

² Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education, Chongqing 400067, China

³ Chongqing Engineering Research Center of Functional Food, Chongqing University of Education, Chongqing 400067, China

⁴ Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing 400067, China

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 239; https://doi.org/10.3390/molecules23020239 - 25 Jan 2018

Cited by 81 | Viewed by 8419

Abstract

Polysaccharides are closely associated with immune regulation, but there are different polysaccharide effects from different sources. In this study, the aim was to investigate the effect of tremella polysaccharides (TP) in cyclophosphamide-induced immunodeficient mice. We observed the thymus and spleen index, liver and [...] Read more.

Polysaccharides are closely associated with immune regulation, but there are different polysaccharide effects from different sources. In this study, the aim was to investigate the effect of tremella polysaccharides (TP) in cyclophosphamide-induced immunodeficient mice. We observed the thymus and spleen index, liver and spleen pathological changes, and the levels of IL-2, IL-12, INF-γ, TGF-β and Ig G in serum, and we also noted the mRNA expression of IL-1β, IL-4, IL-12 and TGF-β in liver and spleen. Besides, we also measured the best effects of different doses of TP (Low-TP was 20 mg/kg·BW, Middle-TP was 40 mg/kg·BW, and High-TP was 80 mg/kg·BW) on cyclophosphamide-induced immunosuppressed mice. The results were remarkable, and suggested that TP had a significant effect for enhancing immunity in cyclophosphamide-induced immunosuppression, and the immune enhancement of High-TP had the best results in TP-treated mice. It could significantly increase the thymus and spleen index, alleviate pathological features of immunosuppression such as the arrangement of liver sinusoid and hepatic plates was disordered, massive inflammatory cells infiltrated and fatty degeneration of hepatocytes in liver, and red pulp and white pulp were intermixed, splenic corpuscles demolished and disappeared, splenic sinusoid extended, and lymphocytes of spleen were reduced in spleen. Besides, it could also up-regulate serum levels of IL-2, IL-12, INF-γ and Ig G, reduce the level of TGF-β in serum, markedly promote mRNA expression of IL-1β, IL-4 and IL-12 in liver and spleen, and suppress mRNA expression of TGF-β. Above all, TP showed preventive effect for cyclophosphamide-induced immunosuppressed mice. Full article

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15 pages, 3469 KiB

Open AccessArticle

Anti-Tumor and Radiosensitization Effects of N-Butylidenephthalide on Human Breast Cancer Cells

by Yi-Ju Su¹, Sung-Ying Huang², Yu-Hui Ni³, Kuan-Fu Liao^4,5 and Sheng-Chun Chiu^3,6,7,*

¹ Department of Radiation Oncology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 42743, Taiwan

² Department of Ophthalmology, Hsinchu Mackay Memorial Hospital, Hsinchu 30071, Taiwan

³ Department of Research, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 42743, Taiwan

⁴ Graduate Institute of Integrated Medicine, China Medical University, Taichung 40402, Taiwan

⁵ Department of Internal Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 42743, Taiwan

⁶ Department of Laboratory Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 42743, Taiwan

⁷ General Education Center, Tzu Chi University of Science and Technology, Hualien 97005, Taiwan

Molecules 2018, 23(2), 240; https://doi.org/10.3390/molecules23020240 - 25 Jan 2018

Cited by 18 | Viewed by 5480

Abstract

N-Butylidenephthalide (BP), which is extracted from a traditional Chinese medicine, Radix Angelica Sinensis (danggui), displays antitumor activity against various cancer cell lines. The purpose of this study was to investigate the cytotoxic and radiosensitizing effect of BP and the underlying [...] Read more.

N-Butylidenephthalide (BP), which is extracted from a traditional Chinese medicine, Radix Angelica Sinensis (danggui), displays antitumor activity against various cancer cell lines. The purpose of this study was to investigate the cytotoxic and radiosensitizing effect of BP and the underlying mechanism of action in human breast cancer cells. BP induces apoptosis in breast cancer cells, which was revealed by the TUNEL assay; the activation of caspase-9 and PARP was detected by western blot. In addition, BP-induced G2/M arrest was examined by flow cytometry and the expression levels of the G2/M regulatory protein were detected by western blot. BP also suppresses the migration and invasion of breast cancer cells, which was tested by wound healing and the matrigel invasion assay; the involvement of EMT-related gene expressions was detected by real-time PCR. Furthermore, BP enhanced the radiosensitivity of breast cancer cells, which was measured by the colony formation assay and comet assay, where the foci of γ-H2AX after radiation significantly increased in BP pretreated cells and was evidenced by immunocytochemistry staining and western blot. The homologous recombination (HR) repair protein Rad51 was down-regulated after BP pretreatment. These results indicate that BP might be a potential chemotherapeutic and radiosensitizing agent for breast cancer therapy. Full article

(This article belongs to the Collection Natural Products: Anticancer Potential and Beyond)

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10 pages, 1055 KiB

Open AccessArticle

Multispecies Adulteration Detection of Camellia Oil by Chemical Markers

by Xinjing Dou^1,2,†, Jin Mao^1,4,5,†, Liangxiao Zhang^1,3,5,6,*

, Huali Xie^1,2, Lin Chen^1,3, Li Yu^1,3, Fei Ma^1,5, Xiupin Wang^1,5, Qi Zhang^1,4 and Peiwu Li^1,3,4,5,*

¹ Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, Wuhan 430062, China

² Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture, Wuhan 430062, China

³ Laboratory of Quality and Safety Risk Assessment for Oilseed Products (Wuhan), Ministry of Agriculture, Wuhan 430062, China

⁴ Key Laboratory of Detection for Mycotoxins, Ministry of Agriculture, Wuhan 430062, China

⁵ Quality Inspection and Test Center for Oilseed Products, Ministry of Agriculture, Wuhan 430062, China

⁶ Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, Wuhan 430062, China

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 241; https://doi.org/10.3390/molecules23020241 - 25 Jan 2018

Cited by 26 | Viewed by 4796

Abstract

Adulteration of edible oils has attracted attention from more researchers and consumers in recent years. Complex multispecies adulteration is a commonly used strategy to mask the traditional adulteration detection methods. Most of the researchers were only concerned about single targeted adulterants, however, it [...] Read more.

Adulteration of edible oils has attracted attention from more researchers and consumers in recent years. Complex multispecies adulteration is a commonly used strategy to mask the traditional adulteration detection methods. Most of the researchers were only concerned about single targeted adulterants, however, it was difficult to identify complex multispecies adulteration or untargeted adulterants. To detect adulteration of edible oil, identification of characteristic markers of adulterants was proposed to be an effective method, which could provide a solution for multispecies adulteration detection. In this study, a simple method of multispecies adulteration detection for camellia oil (adulterated with soybean oil, peanut oil, rapeseed oil) was developed by quantifying chemical markers including four isoflavones, trans-resveratrol and sinapic acid, which used liquid chromatography tandem mass spectrometry (LC-MS/MS) combined with solid phase extraction (SPE). In commercial camellia oil, only two of them were detected of daidzin with the average content of 0.06 ng/g while other markers were absent. The developed method was highly sensitive as the limits of detection (LODs) ranged from 0.02 ng/mL to 0.16 ng/mL and the mean recoveries ranged from 79.7% to 113.5%, indicating that this method was reliable to detect potential characteristic markers in edible oils. Six target compounds for pure camellia oils, soybean oils, peanut oils and rapeseed oils had been analyzed to get the results. The validation results indicated that this simple and rapid method was successfully employed to determine multispecies adulteration of camellia oil adulterated with soybean, peanut and rapeseed oils. Full article

(This article belongs to the Section Analytical Chemistry)

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23 pages, 6366 KiB

Open AccessArticle

Study of the Direct Red 81 Dye/Copper(II)-Phenanthroline System

by Elsa Walger^1,*, Nathalie Marlin¹, Florian Molton²

and Gérard Mortha¹

¹ Univ. Grenoble Alpes, CNRS, Grenoble INP, LGP2, 461 rue de la Papeterie—CS 10065, 38402 Saint Martin d’Hères Cedex, F-38000 Grenoble, France

² Univ. Grenoble Alpes, CNRS, DCM, CS 40700, 38058 Grenoble Cedex 9, F-38000 Grenoble, France

Molecules 2018, 23(2), 242; https://doi.org/10.3390/molecules23020242 - 25 Jan 2018

Cited by 12 | Viewed by 8930

Abstract

Recovered papers contain several chromophores, such as wood lignin and dyes. These have to be eliminated during paper recycling in order to produce white paper. Hydrogen peroxide under alkaline conditions is generally used to decolorize lignin, but its effect on dyes is limited. [...] Read more.

Recovered papers contain several chromophores, such as wood lignin and dyes. These have to be eliminated during paper recycling in order to produce white paper. Hydrogen peroxide under alkaline conditions is generally used to decolorize lignin, but its effect on dyes is limited. Copper(II)-phenanthroline (Cu-Phen) complexes can activate the oxidation of lignin by hydrogen peroxide. Hydrogen peroxide may also be activated during recycled fiber bleaching, thus enhancing its color-stripping efficiency towards unoxidizable azo dyes. The purpose of this paper was to determine the effect of Cu-Phen complexes on a model azo dye, Direct Red 81 (DR81), in aqueous solution. Different Cu-Phen solutions (with different initial Cu:Phen molar ratios) were prepared and mixed with the dye at different pHs. The geochemical computer program PHREEQC allowed precise calculation of the theoretical distribution between different possible coordinates (CuPhenOH⁺, Cu(Phen)₂²⁺, CuPhen(OH)₂, Cu(Phen)₃²⁺, etc.) depending on pH and initial concentrations. UV-vis spectroscopic measurements were correlated with the major species theoretically present in each condition. The UV absorbance of the system was mainly attributed to the Cu-Phen complex and the visible absorbance was only due to the dye. Cu-Phen appeared to reduce the color intensity of the DR81 dye aqueous solution under specific conditions (more effective at pH 10.7 with Cu:Phen = 1:1), probably owing to the occurrence of a coordination phenomenon between DR81 and Cu-Phen. Hence, the ligand competition between phenanthroline and hydroxide ions would be disturbed by a third competitor, which is the dye molecule. Further investigation proved that the DR81 dye is able to form a complex with copper-phenanthroline, leading to partial color-stripping. This new “color-stripping effect” may be a new opportunity in paper and textile industries for wastewater treatment. Full article

(This article belongs to the Section Green Chemistry)

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16 pages, 4684 KiB

Open AccessArticle

HPLC-PDA Combined with Chemometrics for Quantitation of Active Components and Quality Assessment of Raw and Processed Fruits of Xanthium strumarium L.

by Hai Jiang^1,†, Liu Yang^1,†, Xudong Xing¹

, Meiling Yan¹, Xinyue Guo¹, Bingyou Yang¹, Qiuhong Wang^1,2,* and Haixue Kuang^1,*

¹ Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China

² School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 528458, China

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 243; https://doi.org/10.3390/molecules23020243 - 25 Jan 2018

Cited by 19 | Viewed by 5413

Abstract

As a valuable herbal medicine, the fruits of Xanthium strumarium L. (Xanthii Fructus) have been widely used in raw and processed forms to achieve different therapeutic effects in practice. In this study, a comprehensive strategy was proposed for evaluating the active components in [...] Read more.

As a valuable herbal medicine, the fruits of Xanthium strumarium L. (Xanthii Fructus) have been widely used in raw and processed forms to achieve different therapeutic effects in practice. In this study, a comprehensive strategy was proposed for evaluating the active components in 30 batches of raw and processed Xanthii Fructus (RXF and PXF) samples, based on high-performance liquid chromatography coupled with photodiode array detection (HPLC-PDA). Twelve common peaks were detected and eight compounds of caffeoylquinic acids were simultaneously quantified in RXF and PXF. All the analytes were detected with satisfactory linearity (R² > 0.9991) over wide concentration ranges. Simultaneously, the chemically latent information was revealed by hierarchical cluster analysis (HCA) and principal component analysis (PCA). The results suggest that there were significant differences between RXF and PXF from different regions in terms of the content of eight caffeoylquinic acids. Potential chemical markers for XF were found during processing by chemometrics. Full article

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14 pages, 3017 KiB

Open AccessArticle

Complete Chloroplast Genome Sequence and Phylogenetic Analysis of Paeonia ostii

by Shuai Guo^1,2,†, Lili Guo^1,†, Wei Zhao^1,†, Jiang Xu², Yuying Li¹, Xiaoyan Zhang^2,3, Xiaofeng Shen², Mingli Wu^2,4 and Xiaogai Hou^1,*

¹ College of Agricultural (College of Tree Peony), Henan University of Science and Technology, Luoyang 471023, Henan, China

² Institute of Chinese Materia Medical, China Academy of Chinese Medical Sciences, Beijing 100700, China

³ College of Life Science, Huaibei Normal University, Huaibei 235000, Anhui, China

⁴ College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, Hubei China

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 246; https://doi.org/10.3390/molecules23020246 - 26 Jan 2018

Cited by 59 | Viewed by 6660

Abstract

Paeonia ostii, a common oil-tree peony, is important ornamentally and medicinally. However, there are few studies on the chloroplast genome of Paeonia ostii. We sequenced and analyzed the complete chloroplast genome of P. ostii. The size of the P. ostii [...] Read more.

Paeonia ostii, a common oil-tree peony, is important ornamentally and medicinally. However, there are few studies on the chloroplast genome of Paeonia ostii. We sequenced and analyzed the complete chloroplast genome of P. ostii. The size of the P. ostii chloroplast genome is 152,153 bp, including a large single-copy region (85,373 bp), a small single-copy region (17,054 bp), and a pair of inverted repeats regions (24,863 bp). The P. ostii chloroplast genome encodes 111 genes, including 77 protein-coding genes, four ribosomal RNA genes, and 30 transfer RNA genes. The genome contains forward repeats (22), palindromic repeats (28), and tandem repeats (24). The presence of rich simple-sequence repeat loci in the genome provides opportunities for future population genetics work for breeding new varieties. A phylogenetic analysis showed that P. ostii is more closely related to Paeonia delavayi and Paeonia ludlowii than to Paeonia obovata and Paeonia veitchii. The results of this study provide an assembly of the whole chloroplast genome of P. ostii, which may be useful for future breeding and further biological discoveries. It will provide a theoretical basis for the improvement of peony yield and the determination of phylogenetic status. Full article

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19 pages, 2107 KiB

Open AccessArticle

Effect of Temperature on Flavor Compounds and Sensory Characteristics of Maillard Reaction Products Derived from Mushroom Hydrolysate

by Xiao Chen^1,2, Jingyang Yu¹, Heping Cui¹, Shuqin Xia¹, Xiaoming Zhang^1,* and Baoru Yang^2,*

¹ State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, Jiangsu, China

² Food Chemistry and Food Development, Department of Biochemistry, University of Turku, FI-20014 Turku, Finland

Molecules 2018, 23(2), 247; https://doi.org/10.3390/molecules23020247 - 26 Jan 2018

Cited by 65 | Viewed by 7353

Abstract

Maillard reaction products (MRPs) were prepared from mushroom hydrolysate (MH) by heating with d-xylose and l-cysteine at various temperatures (100 °C–140 °C) for 2 h at a pH of 7.4. The sensory characteristics of MH and MRPs were evaluated by panelists [...] Read more.

Maillard reaction products (MRPs) were prepared from mushroom hydrolysate (MH) by heating with d-xylose and l-cysteine at various temperatures (100 °C–140 °C) for 2 h at a pH of 7.4. The sensory characteristics of MH and MRPs were evaluated by panelists and volatile compounds were analyzed by GC/MS. Additionally, partial least squares regression (PLSR) was performed to analyze the correlation between quantitative sensory characteristics and GC/MS data. GC/MS results revealed that higher reaction temperature resulted in more nitrogen and sulfur containing compounds in MRPs while alcohols, ketones and aldehydes were the major flavor compounds obtained in MH. PLSR results showed that 3-phenylfuran and 2-octylfuran were the compounds responsible for the caramel-like flavor; 1-octen-3-ol, (E)-2-octen-1-ol and geranyl acetone were significantly and positively correlated to mushroom-like flavor, whereas, 2-thiophene-carboxaldehyde, 2,5-thiophenedicarboxaldehyde and 3-methylbutanal positively affected MRPs meat-like attribute. Overall, 125 °C was identified as the optimal temperature for preparing MRPs with abundant volatile compounds and favorable sensory characteristics; the concentration of free amino acids and 5′-GMP, which are associated with the umami taste, in MRPs derived under 125 °C were 3 to 4 times higher than those in MH. Full article

(This article belongs to the Collection Recent Advances in Flavors and Fragrances)

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8 pages, 541 KiB

Open AccessArticle

Sesquiterpene Lactones from Vernonia cinerascens Sch. Bip. and Their in Vitro Antitrypanosomal Activity

by Njogu M. Kimani¹

, Josphat C. Matasyoh², Marcel Kaiser^3,4

, Reto Brun^3,4 and Thomas J. Schmidt^1,*

¹ Institute of Pharmaceutical Biology and Phytochemistry (IPBP), University of Münster, PharmaCampus Corrensstraße 48, D-48149 Münster, Germany

² Department of Chemistry, Egerton University, P.O. Box 536, Egerton 20115, Kenya

³ Swiss Tropical and Public Health Institute (Swiss TPH), Socinstr. 57, CH-4051 Basel, Switzerland

⁴ University of Basel, Petersplatz 1, CH-4003 Basel, Switzerland

Molecules 2018, 23(2), 248; https://doi.org/10.3390/molecules23020248 - 27 Jan 2018

Cited by 21 | Viewed by 4623

Abstract

In the endeavor to obtain new antitrypanosomal agents, particularly sesquiterpene lactones, from Kenyan plants of the family Asteraceae, Vernonia cinerascens Sch. Bip. was investigated. Bioactivity-guided fractionation and isolation in conjunction with LC/MS-based dereplication has led to the identification of vernodalol (1) [...] Read more.

In the endeavor to obtain new antitrypanosomal agents, particularly sesquiterpene lactones, from Kenyan plants of the family Asteraceae, Vernonia cinerascens Sch. Bip. was investigated. Bioactivity-guided fractionation and isolation in conjunction with LC/MS-based dereplication has led to the identification of vernodalol (1) and isolation of vernodalin (2), 11β,13-dihydrovernodalin (3), 11β,13-dihydrovernolide (4), vernolide (5), 11β,13-dihydrohydroxyvernolide (6), hydroxyvernolide (7), and a new germacrolide type sesquiterpene lactone vernocinerascolide (8) from the dichloromethane extract of V. cinerascens leaves. Compounds 3–8 were characterized by extensive analysis of their 1D and 2D NMR spectroscopic and HR/MS spectrometric data. All the compounds were evaluated for their in vitro biological activity against bloodstream forms of Trypanosoma brucei rhodesiense and for cytotoxicity against the mammalian cell line L6. Vernodalin (2) was the most active compound with an IC₅₀ value of 0.16 µM and a selectivity index of 35. Its closely related congener 11β,13-dihydrovernodalin (3) registered an IC₅₀ value of 1.1 µM and a selectivity index of 4.2. Full article

(This article belongs to the Collection Natural Products as Leads or Drugs against Neglected Tropical Diseases)

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18 pages, 6982 KiB

Open AccessArticle

Interaction between Saikosaponin D, Paeoniflorin, and Human Serum Albumin

by Guo-Wu Liang^1,†, Yi-Cun Chen^2,†, Yi Wang¹, Hong-Mei Wang¹, Xiang-Yu Pan¹, Pei-Hong Chen² and Qing-Xia Niu^1,*

¹ Department of Pathophysiology, Key Immunopharmacology Laboratory, Institute of Inflammation and Immune Diseases, Shantou University Medical College, Guangdong 515041, China

² Department of Pharmacology, Traditional Chinese Medicine Laboratory, Shantou University Medical College, Guangdong 515041, China

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 249; https://doi.org/10.3390/molecules23020249 - 27 Jan 2018

Cited by 17 | Viewed by 4641

Abstract

Saikosaponin D (SSD) and paeoniflorin (PF) are the major active constituents of Bupleuri Radix and Paeonia lactiflora Pall, respectively, and have been widely used in China to treat liver and other diseases for many centuries. We explored the binding of SSD/PF to [...] Read more.

Saikosaponin D (SSD) and paeoniflorin (PF) are the major active constituents of Bupleuri Radix and Paeonia lactiflora Pall, respectively, and have been widely used in China to treat liver and other diseases for many centuries. We explored the binding of SSD/PF to human serum albumin (HSA) by using fluorospectrophotometry, circular dichroism (CD) and molecular docking. Both SSD and PF produced a conformational change in HSA. Fluorescence quenching was accompanied by a blue shift in the fluorescence spectra. Co-binding of PF and SSD also induced quenching and a conformational change in HSA. The Stern-Volmer equation showed that quenching was dominated by static quenching. The binding constant for ternary interaction was below that for binary interaction. Site-competitive experiments demonstrated that SSD/PF bound to site I (subdomain IIA) and site II (subdomain IIIA) in HSA. Analysis of thermodynamic parameters indicated that hydrogen bonding and van der Waals forces were mostly responsible for the binary association. Also, there was energy transfer upon binary interaction. Molecular docking supported the experimental findings in conformation, binding sites and binding forces. Full article

(This article belongs to the Collection Herbal Medicine Research)

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18 pages, 1689 KiB

Open AccessArticle

Predicting the Effect of Single and Multiple Mutations on Protein Structural Stability

by Ramin Dehghanpoor^1,†, Evan Ricks^2,†, Katie Hursh², Sarah Gunderson², Roshanak Farhoodi¹, Nurit Haspel¹, Brian Hutchinson^2,3 and Filip Jagodzinski^2,*

¹ Department of Computer Science, University of Massachusetts Boston, Boston, MA 02125, USA

² Department of Computer Science, Western Washington University, Bellingham, WA 98225, USA

³ Computing and Analytics Division, Pacific Northwest National Laboratory; Richland, WA 99354, USA

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 251; https://doi.org/10.3390/molecules23020251 - 27 Jan 2018

Cited by 29 | Viewed by 7584

Abstract

Predicting how a point mutation alters a protein’s stability can guide pharmaceutical drug design initiatives which aim to counter the effects of serious diseases. Conducting mutagenesis studies in physical proteins can give insights about the effects of amino acid substitutions, but such wet-lab [...] Read more.

Predicting how a point mutation alters a protein’s stability can guide pharmaceutical drug design initiatives which aim to counter the effects of serious diseases. Conducting mutagenesis studies in physical proteins can give insights about the effects of amino acid substitutions, but such wet-lab work is prohibitive due to the time as well as financial resources needed to assess the effect of even a single amino acid substitution. Computational methods for predicting the effects of a mutation on a protein structure can complement wet-lab work, and varying approaches are available with promising accuracy rates. In this work we compare and assess the utility of several machine learning methods and their ability to predict the effects of single and double mutations. We in silico generate mutant protein structures, and compute several rigidity metrics for each of them. We use these as features for our Support Vector Regression (SVR), Random Forest (RF), and Deep Neural Network (DNN) methods. We validate the predictions of our in silico mutations against experimental

Δ Δ G

stability data, and attain Pearson Correlation values upwards of 0.71 for single mutations, and 0.81 for double mutations. We perform ablation studies to assess which features contribute most to a model’s success, and also introduce a voting scheme to synthesize a single prediction from the individual predictions of the three models. Full article

(This article belongs to the Special Issue Selected Papers from the 10th Computational Structural Bioinformatics Workshop (CSBW-2017))

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38 pages, 6645 KiB

Open AccessArticle

Systematic Structure-Activity Relationship (SAR) Exploration of Diarylmethane Backbone and Discovery of A Highly Potent Novel Uric Acid Transporter 1 (URAT1) Inhibitor

by Wenqing Cai^1,2,†, Jingwei Wu^2,†, Wei Liu², Yafei Xie², Yuqiang Liu², Shuo Zhang³, Weiren Xu², Lida Tang², Jianwu Wang^1,* and Guilong Zhao^2,*

¹ School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China

² Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China

³ Shandong Key Laboratory for Special Silicon-Containing Materials, Advanced Materials Institute, Shandong Academy of Sciences, Jinan 250014, China

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 252; https://doi.org/10.3390/molecules23020252 - 27 Jan 2018

Cited by 22 | Viewed by 8145

Abstract

In order to systematically explore and better understand the structure-activity relationship (SAR) of a diarylmethane backbone in the design of potent uric acid transporter 1 (URAT1) inhibitors, 33 compounds (1a–1x and 1ha–1hi) were designed and synthesized, and [...] Read more.

In order to systematically explore and better understand the structure-activity relationship (SAR) of a diarylmethane backbone in the design of potent uric acid transporter 1 (URAT1) inhibitors, 33 compounds (1a–1x and 1ha–1hi) were designed and synthesized, and their in vitro URAT1 inhibitory activities (IC₅₀) were determined. The three-round systematic SAR exploration led to the discovery of a highly potent novel URAT1 inhibitor, 1h, which was 200- and 8-fold more potent than parent lesinurad and benzbromarone, respectively (IC₅₀ = 0.035 μM against human URAT1 for 1h vs. 7.18 μM and 0.28 μM for lesinurad and benzbromarone, respectively). Compound 1h is the most potent URAT1 inhibitor discovered in our laboratories so far and also comparable to the most potent ones currently under development in clinical trials. The present study demonstrates that the diarylmethane backbone represents a very promising molecular scaffold for the design of potent URAT1 inhibitors. Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 1642 KiB

Open AccessArticle

N-Salicyloyltryptamine, an N-Benzoyltryptamine Analogue, Induces Vasorelaxation through Activation of the NO/sGC Pathway and Reduction of Calcium Influx

by Robson Cavalcante Veras^1,2,*, Darizy Flávia Silva³, Lorena Soares Bezerra², Valéria Lopes de Assis⁴, Walma Pereira de Vasconcelos⁴, Maria Do Carmo Alustau⁴, José George Ferreira de Albuquerque⁴, Fabíola Fialho Furtado⁴, Islania Giselia de Albuquerque Araújo¹, Fátima De Lourdes Assunção Araújo de Azevedo⁴, Thais Porto Ribeiro⁴, José Maria Barbosa-Filho^1,4, Stanley Juan Chavez Gutierrez⁴ and Isac Almeida Medeiros^1,4

¹ Department of Pharmaceutical Sciences, Federal University of Paraíba (UFPB), João Pessoa 58059-900, Brazil

² Postgraduate Program of Nutrition Science/CCS/Federal University of Paraíba (UFPB)

³ Department of Biorregulation, Federal University of Bahia (UFBA), Av. Reitor Miguel Calmon, S/N, Vale do Canela, Salvador 40110-902, Brazil

⁴ Postgraduate Program of Natural Products and Bioactive Synthetics/CCS/Universidade Federal da Paraíba (UFPB), João Pessoa 58059-900, Brazil

Molecules 2018, 23(2), 253; https://doi.org/10.3390/molecules23020253 - 28 Jan 2018

Viewed by 3156

Abstract

Benzoyltryptamine analogues act as neuroprotective and spasmolytic agents on smooth muscles. In this study, we investigated the ability of N-salicyloyltryptamine (STP) to produce vasorelaxation and determined its underlying mechanisms of action. Isolated rat mesenteric arteries with and without functional endothelium were studied [...] Read more.

Benzoyltryptamine analogues act as neuroprotective and spasmolytic agents on smooth muscles. In this study, we investigated the ability of N-salicyloyltryptamine (STP) to produce vasorelaxation and determined its underlying mechanisms of action. Isolated rat mesenteric arteries with and without functional endothelium were studied in an isometric contraction system in the presence or absence of pharmacological inhibitors. Amperometric experiments were used to measure the nitric oxide (NO) levels in CD31+ cells using flow cytometry. GH3 cells were used to measure Ca²⁺ currents using the whole cell patch clamp technique. STP caused endothelium-dependent and -independent relaxation in mesenteric rings. The endothelial-dependent relaxations in response to STP were markedly reduced by L-NAME (endothelial NO synthase—eNOS—inhibitor), jHydroxocobalamin (NO scavenger, 30 µM) and ODQ (soluble Guanylyl Cyclase—sGC—inhibitor, 10 µM), but were not affected by the inhibition of the formation of vasoactive prostanoids. These results were reinforced by the increased NO levels observed in the amperometric experiments with freshly dispersed CD31+ cells. The endothelium-independent effect appeared to involve the inhibition of voltage-gated Ca²⁺ channels, due to the inhibition of the concentration-response Ca²⁺ curves in depolarizing solution, the increased relaxation in rings that were pre-incubated with high extracellular KCl (80 mM), and the inhibition of macroscopic Ca²⁺ currents. The present findings show that the activation of the NO/sGC/cGMP pathway and the inhibition of gated-voltage Ca²⁺ channels are the mechanisms underlying the effect of STP on mesenteric arteries. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 6090 KiB

Open AccessArticle

The Effect of Ultraviolet Irradiation on the Physicochemical Properties of Poly(vinyl Chloride) Films Containing Organotin(IV) Complexes as Photostabilizers

by Duaa Ghazi¹, Gamal A. El-Hiti^2,*

, Emad Yousif^1,*, Dina S. Ahmed³ and Mohammad Hayal Alotaibi⁴

¹ Department of Chemistry, College of Science, Al-Nahrain University, Baghdad 64021, Iraq

² Cornea Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia

³ Department of Chemistry, College of Science, Tikrit University, Tikrit 34001, Iraq

⁴ Center of Excellence in Integrated Nano-Systems, King Abdulaziz City for Science and Technology, P.O. Box 6086, Riyadh 11442, Saudi Arabia

Molecules 2018, 23(2), 254; https://doi.org/10.3390/molecules23020254 - 28 Jan 2018

Cited by 49 | Viewed by 4448

Abstract

Three organotin(IV) complexes containing ciprofloxacin as a ligand (Ph₃SnL, Me₂SnL₂ and Bu₂SnL₂; 0.5% by weight) were used as additives to inhibit the photodegradation of polyvinyl chloride films (40 µm thickness) upon irradiation with ultraviolet [...] Read more.

Three organotin(IV) complexes containing ciprofloxacin as a ligand (Ph₃SnL, Me₂SnL₂ and Bu₂SnL₂; 0.5% by weight) were used as additives to inhibit the photodegradation of polyvinyl chloride films (40 µm thickness) upon irradiation with ultraviolet light (λ_max = 313 at a light intensity = 7.75 × 10⁻⁷ ein dm⁻³ S⁻¹) at room temperature. The efficiency of organotin(IV) complexes as photostabilizers was determined by monitoring the changes in the weight, growth of specific functional groups (hydroxyl, carbonyl and carbene), viscosity, average molecular weight, chain scission and degree of deterioration of the polymeric films upon irradiation. The results obtained indicated that organotin(IV) complexes stabilized poly(vinyl chloride) and the dimethyltin(IV) complex was the most efficient additive. The surface morphologies of poly(vinyl chloride) films containing organotin(IV) complexes were examined using an atomic force microscope and scanning electron microscopy. These showed that the surface of polymeric films containing organotin(IV) complexes were smoother and less rough, compared to the surface of the blank films. Some mechanisms that explained the role of organotin(IV) complexes in poly(vinyl chloride) photostabilization process were proposed. Full article

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8 pages, 795 KiB

Open AccessCommunication

Novel Topologically Complex Scaffold Derived from Alkaloid Haemanthamine

by Karthik Govindaraju¹, Marco Masi²

, Margaux Colin³, Veronique Mathieu³, Antonio Evidente², Todd W. Hudnall^1,* and Alexander Kornienko^1,*

¹ Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, USA

² Dipartimento di Scienze Chimiche, Università di Napoli Federico II, Complesso Universitario Monte Sant’Angelo, Via Cintia 4, 80126 Napoli, Italy

³ Department of Pharmacotherapy and Pharmaceutics, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), 1050 Brussels, Belgium

Molecules 2018, 23(2), 255; https://doi.org/10.3390/molecules23020255 - 28 Jan 2018

Cited by 12 | Viewed by 4318

Abstract

The generation of natural product-like compound collections has become an important area of research due to low hit rates found with synthetic high-throughput libraries. One method of generating compounds occupying the areas of chemical space not accessible to synthetic planar heterocyclic structures is [...] Read more.

The generation of natural product-like compound collections has become an important area of research due to low hit rates found with synthetic high-throughput libraries. One method of generating compounds occupying the areas of chemical space not accessible to synthetic planar heterocyclic structures is the utilization of natural products as starting materials. In the current work, using a ring-closing iodoalkoxylation reaction, alkaloid haemanthamine was transformed into a unique structural framework possessing an intricate ring system and a large number of stereocenters. The structure of the new compound was confirmed with an X-ray analysis. A small number of derivatives of this new compound were synthesized as a demonstration of the possibility of generating a large natural product-like compound collection based on the new structural framework. Full article

(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products 2018)

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11 pages, 538 KiB

Open AccessArticle

Nigella damascena L. Essential Oil—A Valuable Source of β-Elemene for Antimicrobial Testing

by Elwira Sieniawska^1,*

, Rafal Sawicki^2,*, Joanna Golus², Marta Swatko-Ossor²

, Grazyna Ginalska² and Krystyna Skalicka-Wozniak¹

¹ Department of Pharmacognosy with Medicinal Plant Unit, Medical University of Lublin, Chodzki 1 Street, 20-093 Lublin, Poland

² Department of Biochemistry and Biotechnology, Medical University of Lublin, Chodzki 1 Street, 20-093 Lublin, Poland

Molecules 2018, 23(2), 256; https://doi.org/10.3390/molecules23020256 - 28 Jan 2018

Cited by 30 | Viewed by 5939

Abstract

The most commonly used plant source of β-elemene is Curcuma wenyujin Y. H. Chen & C. Ling (syn. of Curcuma aromatic Salisb.) with its content in supercritical CO₂ extract up to 27.83%. However, the other rich source of this compound is Nigella [...] Read more.

The most commonly used plant source of β-elemene is Curcuma wenyujin Y. H. Chen & C. Ling (syn. of Curcuma aromatic Salisb.) with its content in supercritical CO₂ extract up to 27.83%. However, the other rich source of this compound is Nigella damascena L. essential oil, in which β-elemene accounts for 47%. In this work, the effective protocol for preparative isolation of β-elemene from a new source—N. damascena essential oil—using high performance counter-current chromatography HPCCC was elaborated. Furthermore, since sesquiterpens are known as potent antimicrobials, the need for finding new agents designed to combat multi-drug resistant strains was addressed and the purified target compound and the essential oil were tested for its activity against a panel of Gram-positive and Gram-negative bacteria, fungi, and mycobacterial strains. The application of the mixture of petroleum ether, acetonitrile, and acetone in the ratio 2:1.5:0.5 (v/v) in the reversed phase mode yielded β-elemene with high purity in 70 min. The results obtained for antimicrobial assay clearly indicated that N. damascena essential oil and isolated β-elemene exert action against Mycobacterium tuberculosis strain H37Ra. Full article

(This article belongs to the Special Issue Diversity of Terpenoids)

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15 pages, 2224 KiB

Open AccessFeature PaperArticle

In Silico and in Vitro-Guided Identification of Inhibitors of Alkylquinolone-Dependent Quorum Sensing in Pseudomonas aeruginosa

by Fadi Soukarieh¹

, Eduard Vico Oton¹, Jean-Frédéric Dubern¹, Janice Gomes¹, Nigel Halliday¹, Maria De Pilar Crespo², Jonathan Ramírez-Prada³, Braulio Insuasty³, Rodrigo Abonia³, Jairo Quiroga³

, Stephan Heeb¹

, Paul Williams¹, Michael J. Stocks⁴

and Miguel Cámara^1,*

¹ School of Life Sciences, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK

² Department of Microbiology, Universidad del Valle and Departamento of Biomedical Sciences, Universidad Santiago de Cali, Cali AA 760035, Colombia

³ Department of Chemistry, Universidad del Valle, Cali AA 25360, Colombia

⁴ School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK

Molecules 2018, 23(2), 257; https://doi.org/10.3390/molecules23020257 - 28 Jan 2018

Cited by 48 | Viewed by 8769

Abstract

Pseudomonas aeruginosa is a major opportunistic pathogen in cystic fibrosis, wound and nosocomial infections, posing a serious burden to public health, due to its antibiotic resistance. The P. aeruginosa Pseudomonas Quinolone System (pqs) quorum sensing system, driven by the activation of [...] Read more.

Pseudomonas aeruginosa is a major opportunistic pathogen in cystic fibrosis, wound and nosocomial infections, posing a serious burden to public health, due to its antibiotic resistance. The P. aeruginosa Pseudomonas Quinolone System (pqs) quorum sensing system, driven by the activation of the transcriptional regulator, PqsR (MvfR) by alkylquinolone (AQ) signal molecules, is a key player in the regulation of virulence and a potential target for the development of novel antibacterial agents. In this study, we performed in silico docking analysis, coupled with screening using a P. aeruginosa mCTX::P_pqsA-lux chromosomal promoter fusion, to identify a series of new PqsR antagonists. The hit compounds inhibited pyocyanin and alkylquinolone signal molecule production in P. aeruginosa PAO1-L and PA14 strains. The inhibitor Ia, which showed the highest activity in PA14, reduced biofilm formation in PAO1-L and PA14, increasing their sensitivity to tobramycin. Furthermore, the hepatic and plasma stabilities for these compounds were determined in both rat and human in vitro microsomal assays, to gain a further understanding of their therapeutic potential. This work has uncovered a new class of P. aeruginosa PqsR antagonists with potential for hit to lead optimisation in the search for quorum sensing inhibitors for future anti-infective drug discovery programs. Full article

(This article belongs to the Special Issue Design and Synthesis of Quorum-Sensing Inhibitors)

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23 pages, 3903 KiB

Open AccessArticle

Study of the Anti-Staphylococcal Potential of Honeys Produced in Northern Poland

by Katarzyna Grecka¹

, Piotr M. Kuś²

, Randy W. Worobo³

and Piotr Szweda^1,*

¹ Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdańsk University of Technology, ul. G. Narutowicza 11/12, 80-233 Gdańsk, Poland

² Department of Pharmacognosy, Wrocław Medical University, ul. Borowska 211a, 50-556 Wrocław, Poland

³ Department of Food Science, Cornell University, Ithaca, NY 14853, USA

Molecules 2018, 23(2), 260; https://doi.org/10.3390/molecules23020260 - 28 Jan 2018

Cited by 58 | Viewed by 6489

Abstract

The antimicrobial activity of 144 samples of honeys including 95 products from apiaries located in Northern Poland was evaluated. The antibacterial activity of those natural products, their thermal stability, and activity in the presence of catalase was investigated by microdilution assays in titration [...] Read more.

The antimicrobial activity of 144 samples of honeys including 95 products from apiaries located in Northern Poland was evaluated. The antibacterial activity of those natural products, their thermal stability, and activity in the presence of catalase was investigated by microdilution assays in titration plates. The MTT assay was performed for the determination of anti-biofilm activity. Spectrophotometric assays were used for the determination of antioxidant potential, total phenolic content, and ability to generate hydrogen peroxide. Some of the investigated honeys exhibited surprisingly high antimicrobial, especially anti-staphylococcal, potential, with Minimal Inhibitory Concentration (MIC) values of only 1.56% (v/v). Much higher resistance was observed in the case of staphylococci growing as biofilms. Lower concentrations of the product, up to 12.5% (v/v) stimulated its growth and effective eradication of biofilm required concentration of at least 25% (v/v). Hydrogen peroxide has been identified as a crucial contributor to the antimicrobial activity of honeys supplied by Polish beekeepers. However, some of the results suggest that phytochemicals, especially polyphenols, play an important role depending on botanical source (both positive, e.g., in the case of buckwheat honeys as well as negative, e.g., in the case of some rapeseed honeys) in their antimicrobial potential. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 1311 KiB

Open AccessArticle

Food-Grade Synthesis of Maillard-Type Taste Enhancers Using Natural Deep Eutectic Solvents (NADES)

by Maximilian Kranz and Thomas Hofmann^*

Chair of Food Chemistry and Molecular and Sensory Science, Technical University of Munich, Lise-Meitner-Str. 34, D-85354 Freising, Germany

Molecules 2018, 23(2), 261; https://doi.org/10.3390/molecules23020261 - 28 Jan 2018

Cited by 32 | Viewed by 7130

Abstract

The increasing demand for healthier food products, with reduced levels of table salt, sugar, and mono sodium glutamate, reinforce the need for novel taste enhancers prepared by means of food-grade kitchen-type chemistry. Although several taste modulating compounds have been discovered in processed foods, [...] Read more.

The increasing demand for healthier food products, with reduced levels of table salt, sugar, and mono sodium glutamate, reinforce the need for novel taste enhancers prepared by means of food-grade kitchen-type chemistry. Although several taste modulating compounds have been discovered in processed foods, their Maillard-type ex food production is usually not exploited by industrial process reactions as the yields of target compounds typically do not exceed 1–2%. Natural deep eutectic solvents (NADES) are reported for the first time to significantly increase the yields of the taste enhancers 1-deoxy-d-fructosyl-N-β-alanyl-l-histidine (49% yield), N-(1-methyl-4-oxoimidazolidin-2-ylidene) aminopropionic acid (54% yield) and N²-(1-carboxyethyl) guanosine 5′-monophosphate (22% yield) at low temperature (80–100 °C) within a maximum reaction time of 2 h. Therefore, NADES open new avenues to a “next-generation culinary chemistry” overcoming the yield limitations of traditional Maillard chemistry approaches and enable a food-grade Maillard-type generation of flavor modulators. Full article

(This article belongs to the Section Green Chemistry)

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11 pages, 2328 KiB

Open AccessCommunication

Analysis of Protein-Phenolic Compound Modifications Using Electrochemistry Coupled to Mass Spectrometry

by Constanze Kallinich, Simone Schefer and Sascha Rohn^*

Institute of Food Chemistry, Hamburg School of Food Science, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany

Molecules 2018, 23(2), 264; https://doi.org/10.3390/molecules23020264 - 29 Jan 2018

Cited by 8 | Viewed by 5332

Abstract

In the last decade, electrochemical oxidation coupled with mass spectrometry has been successfully used for the analysis of metabolic studies. The application focused in this study was to investigate the redox potential of different phenolic compounds such as the very prominent chlorogenic acid. [...] Read more.

In the last decade, electrochemical oxidation coupled with mass spectrometry has been successfully used for the analysis of metabolic studies. The application focused in this study was to investigate the redox potential of different phenolic compounds such as the very prominent chlorogenic acid. Further, EC/ESI-MS was used as preparation technique for analyzing adduct formation between electrochemically oxidized phenolic compounds and food proteins, e.g., alpha-lactalbumin or peptides derived from a tryptic digestion. In the first step of this approach, two reactant solutions are combined and mixed: one contains the solution of the digested protein, and the other contains the phenolic compound of interest, which was, prior to the mixing process, electrochemically transformed to several oxidation products using a boron-doped diamond working electrode. As a result, a Michael-type addition led to covalent binding of the activated phenolic compounds to reactive protein/peptide side chains. In a follow-up approach, the reaction mix was further separated chromatographically and finally detected using ESI-HRMS. Compound-specific, electrochemical oxidation of phenolic acids was performed successfully, and various oxidation and reaction products with proteins/peptides were observed. Further optimization of the reaction (conditions) is required, as well as structural elucidation concerning the final adducts, which can be phenolic compound oligomers, but even more interestingly, quite complex mixtures of proteins and oxidation products. Full article

(This article belongs to the Special Issue Protein Modifications and Bioconjugation)

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15 pages, 3181 KiB

Open AccessArticle

Effect of Melatonin on the Renin-Angiotensin-Aldosterone System in l-NAME-Induced Hypertension

by Fedor Simko^1,2,3,*, Tomas Baka¹, Kristina Krajcirovicova¹, Kristina Repova¹

, Silvia Aziriova¹, Stefan Zorad³, Marko Poglitsch⁴, Michaela Adamcova⁵, Russel J. Reiter^6,† and Ludovit Paulis^1,7,†

¹ Institute of Pathophysiology, Faculty of Medicine, Comenius University, Sasinkova 4, 81108 Bratislava, Slovakia

² 3rd Department of Internal Medicine, Faculty of Medicine, Comenius University, 83305 Bratislava, Slovakia

³ Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, 84505 Bratislava, Slovakia

⁴ Attoquant Diagnostics, 1030 Vienna, Austria

⁵ Department of Physiology, School of Medicine, Charles University, 50003 Hradec Kralove, Czech Republic

⁶ Department of Cellular and Structural Biology, UT Health Science Center, San Antonio, TX 78229, USA

⁷ Institute of Normal and Pathological Physiology, Center for Experimental Medicine, Slovak Academy of Sciences, 81371 Bratislava, Slovakia

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 265; https://doi.org/10.3390/molecules23020265 - 29 Jan 2018

Cited by 46 | Viewed by 7706

Abstract

The renin-angiotensin-aldosterone system (RAAS) is a dominant player in several cardiovascular pathologies. This study investigated whether alterations induced by l-NAME, (NLG)-nitro-l-arginine methyl ester, a nitric oxide synthase inhibitor, and the protective effect of melatonin are associated with changes in the [...] Read more.

The renin-angiotensin-aldosterone system (RAAS) is a dominant player in several cardiovascular pathologies. This study investigated whether alterations induced by l-NAME, (NLG)-nitro-l-arginine methyl ester, a nitric oxide synthase inhibitor, and the protective effect of melatonin are associated with changes in the RAAS. Four groups of 3-month-old male Wistar rats (n = 10) were treated as follows for four weeks: untreated controls, rats treated with melatonin (10 mg/kg/day), rats treated with l-NAME (40 mg/kg/day), and rats treated with l-NAME + melatonin. l-NAME administration led to hypertension and left ventricular (LV) fibrosis in terms of enhancement of soluble, insoluble and total collagen concentration and content. Melatonin reduced systolic blood pressure enhancement and lowered the concentration and content of insoluble and total collagen in the LV. The serum concentration of angiotensin (Ang) 1–8 (Ang II) and its downstream metabolites were reduced in the l-NAME group and remained unaltered by melatonin. The serum aldosterone level and its ratio to Ang II (AA2-ratio) were increased in the l-NAME group without being modified by melatonin. We conclude that l-NAME-hypertension is associated with reduced level of Ang II and its downstream metabolites and increased aldosterone concentration and AA2-ratio. Melatonin exerts its protective effect in l-NAME-induced hypertension without affecting RAAS. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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11 pages, 1269 KiB

Open AccessArticle

Synthesis, DNA Binding, and Anticancer Properties of Bis-Naphthalimide Derivatives with Lysine-Modified Polyamine Linkers

by Yu Huang^1,*, Chun-Xia Wu¹, Yu Song¹, Min Huang², Da-Nian Tian², Xin-Bin Yang³ and Yan-Ru Fan^1,*

¹ Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Engineering and Technology Research Centre of Hui Medicine Modernization, College of Pharmacy, Ningxia Medical University, Yinchuan 750004, China

² College of Public Health, Ningxia Medical University, Yinchuan 750004, China

³ Rongchang Campus, Southwest University, Chongqing 402460, China

Molecules 2018, 23(2), 266; https://doi.org/10.3390/molecules23020266 - 29 Jan 2018

Cited by 13 | Viewed by 4165

Abstract

A series of bis-naphthalimide derivatives with different diamine linkers were designed and synthesized. All of the synthesized bis-naphthalimide derivatives were characterized by NMR and HRMS spectra. The binding ability between the compounds and CT DNA was evaluated by using UV–Vis titration experiments. The [...] Read more.

A series of bis-naphthalimide derivatives with different diamine linkers were designed and synthesized. All of the synthesized bis-naphthalimide derivatives were characterized by NMR and HRMS spectra. The binding ability between the compounds and CT DNA was evaluated by using UV–Vis titration experiments. The bis-naphthalimide compound with an ethylenediamine linker showed the largest binding constant with CT DNA. Hence, it was used as the model compound to study the DNA binding selectivity by UV–Vis titration aiming at different DNA duplexes. As a result, this compound showed binding preference to AT-rich duplexes. The DNA binding modes of the compounds were also measured by viscosity titration. The cytotoxicity of the compounds was evaluated by MTT assay. Compounds with 1,6-diaminohexane or 1,4-phenylenedimethanamine linkers showed higher cytotoxicity compared with other bis-naphthalimide derivatives. Full article

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11 pages, 1242 KiB

Open AccessArticle

Isolation and Quantification of Ginsenoside Rh23, a New Anti-Melanogenic Compound from the Leaves of Panax ginseng

by Dae Young Lee¹

, Hyoung-Geun Kim², Yeong-Geun Lee²

, Jin Hee Kim³, Jae Won Lee¹

, Bo-Ram Choi¹, In-Bae Jang¹, Geum-Soog Kim¹ and Nam-In Baek^2,*

¹ Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 27709, Korea

² Department of Oriental Medicine Biotechnology, Kyung Hee University, Yongin 17104, Korea

³ College of Herbal Bio-industry, Daegu Haany University, Gyeongsan 38610, Korea

Molecules 2018, 23(2), 267; https://doi.org/10.3390/molecules23020267 - 29 Jan 2018

Cited by 19 | Viewed by 5097

Abstract

A new ginsenoside, named ginsenoside Rh23 (1), and 20-O-β-d-glucopyranosyl-3β,6α,12β,20β,25-pentahydroxydammar-23-ene (2) were isolated from the leaves of hydroponic Panax ginseng. Compounds were isolated by various column chromatography and their structures were determined based on spectroscopic [...] Read more.

A new ginsenoside, named ginsenoside Rh23 (1), and 20-O-β-d-glucopyranosyl-3β,6α,12β,20β,25-pentahydroxydammar-23-ene (2) were isolated from the leaves of hydroponic Panax ginseng. Compounds were isolated by various column chromatography and their structures were determined based on spectroscopic methods, including high resolution quadrupole/time of flight mass spectrometry (HR-QTOF/MS), nuclear magnetic resonance (NMR) spectroscopy, and infrared (IR) spectroscopy. To determine anti-melanogenic activity, the change in the melanin content in melan-a cells treated with identified compounds was tested. Additionally, we investigated the melanin inhibitory effects of ginsenoside Rh23 on pigmentation in a zebrafish in vivo model. Compound 1 inhibited potent melanogenesis in melan-a cells with 37.0% melanogenesis inhibition at 80 µM and also presented inhibition on the body pigmentation in zebrafish model. Although compound 2 showed slightly lower inhibitory activity than compound 1, it also showed significantly decreased melanogenesis in melan-a cell and in zebrafish model. These results indicated that compounds isolated from hydroponic P. ginseng may be used as new skin whitening compound through the in vitro and in vivo systems. Furthermore, this study demonstrated the utility of MS-based compound 1 for the quantitative analysis. Ginsenoside Rh23 (1) was found at a level of 0.31 mg/g in leaves of hydroponic P. ginseng. Full article

(This article belongs to the Special Issue Biological Activity of Secondary Metabolites)

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15 pages, 3863 KiB

Open AccessArticle

Anticancer Efficacy of Targeted Shikonin Liposomes Modified with RGD in Breast Cancer Cells

by Xianchun Wen^1,2

, Jiping Li¹, Defu Cai², Liling Yue², Qi Wang², Li Zhou², Li Fan², Jianwen Sun¹ and Yonghui Wu^1,*

¹ Public Health College, Harbin Medical University, Harbin 150081, China

² Research Institute of Medicine & Pharmacy, Qiqihar Medical University, Qiqihar 161006, China

Molecules 2018, 23(2), 268; https://doi.org/10.3390/molecules23020268 - 29 Jan 2018

Cited by 43 | Viewed by 5740

Abstract

Shikonin (SHK) has been proven to have a good anti-tumor effect. However, poor water solubility and low bioavailability limit its wide application in clinical practice. In this study, to overcome these drawbacks, RGD-modified shikonin-loaded liposomes (RGD-SSLs-SHK) were successfully prepared. It exhibited excellent physicochemical [...] Read more.

Shikonin (SHK) has been proven to have a good anti-tumor effect. However, poor water solubility and low bioavailability limit its wide application in clinical practice. In this study, to overcome these drawbacks, RGD-modified shikonin-loaded liposomes (RGD-SSLs-SHK) were successfully prepared. It exhibited excellent physicochemical characteristics including particle size, zeta potential, encapsulation efficiency, and delayed release time. Meanwhile, the targeting activity of the RGD-modified liposomes was demonstrated by flow cytometry and confocal microscopy in the α_vβ₃-positive MDA-MB-231 cells. Besides exhibiting greater cytotoxicity in vitro, compared with non-targeted shikonin-loaded liposomes (SSLs-SHK), RGD-SSLs-SHK could also evidently induce apoptosis by decreasing the expression of Bcl-2 and increasing the expression of Bax. It could also inhibit cell proliferation, migration, invasion, and adhesion by reducing the expression of MMP-9 and the level of NF-κB p65, but did not affect the expression of MMP-2 in the MDA-MB-231 cells. Therefore, these findings indicated that the strategy to use RGD-modified liposomes as carriers for targeted delivery of shikonin is a very promising approach to achieve breast cancer targeted therapy. Full article

(This article belongs to the Special Issue Liposomes as Drug Carriers)

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12 pages, 6475 KiB

Open AccessArticle

Cloning, Expression Analysis and Functional Characterization of Squalene Synthase (SQS) from Tripterygium wilfordii

by Bin Zhang¹, Yan Liu¹, Mengmeng Chen¹, Juntao Feng^1,2, Zhiqing Ma^1,2, Xing Zhang^1,2,* and Chuanshu Zhu^1,2,*

¹ Research & Development Center of Biorational Pesticides, Northwest A & F University, Yangling 712100, China

² Biopesticide Technology and Engineering Center of Shaanxi Province, Yangling 712100, China

Molecules 2018, 23(2), 269; https://doi.org/10.3390/molecules23020269 - 29 Jan 2018

Cited by 21 | Viewed by 4235

Abstract

Celastrol is an active triterpenoid compound derived from Tripterygium wilfordii which is well-known as a traditional Chinese medicinal plant. Squalene synthase has a vital role in condensing two molecules of farnesyl diphosphate to form squalene, a key precursor of triterpenoid biosynthesis. In the [...] Read more.

Celastrol is an active triterpenoid compound derived from Tripterygium wilfordii which is well-known as a traditional Chinese medicinal plant. Squalene synthase has a vital role in condensing two molecules of farnesyl diphosphate to form squalene, a key precursor of triterpenoid biosynthesis. In the present study, T. wilfordii squalene synthase (TwSQS) was cloned followed by prokaryotic expression and functional verification. The open reading frame cDNA of TwSQS was 1242 bp encoding 413 amino acids. Bioinformatic and phylogenetic analysis showed that TwSQS had high homology with other plant SQSs. To obtain soluble protein, the truncated TwSQS without the last 28 amino acids of the carboxy terminus was inductively expressed in Escherichia coli Transetta (DE3). The purified protein was detected by SDS-PAGE and Western blot analysis. Squalene was detected in the product of in vitro reactions by gas chromatograph-mass spectrometry, which meant that TwSQS did have catalytic activity. Organ-specific and inducible expression levels of TwSQS were detected by quantitative real-time PCR. The results indicated that TwSQS was highly expressed in roots, followed by the stems and leaves, and was significantly up-regulated upon MeJA treatment. The identification of TwSQS is important for further studies of celastrol biosynthesis in T. wilfordii. Full article

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11 pages, 1693 KiB

Open AccessArticle

Novel Strategies Using Total Gastrodin and Gastrodigenin, or Total Gastrodigenin for Quality Control of Gastrodia elata

by Chunlan Tang^*, Bingchu Wu, Jinyi Wu, Zheng Zhang and Bocheng Yu

Department of Preventative Medicine, Medical School of Ningbo University, Ningbo 315211, China

Molecules 2018, 23(2), 270; https://doi.org/10.3390/molecules23020270 - 29 Jan 2018

Cited by 22 | Viewed by 4241

Abstract

Gastrodia elata Blume (G. elata), a traditional Chinese medicine, is widely used for treatment of various neuro dysfunctions. However, its quality control is still limited to the determination of gastrodin. In the present study, two novel strategies based on quantitative evaluation [...] Read more.

Gastrodia elata Blume (G. elata), a traditional Chinese medicine, is widely used for treatment of various neuro dysfunctions. However, its quality control is still limited to the determination of gastrodin. In the present study, two novel strategies based on quantitative evaluation of total gastrodin and gastrodigenin with base hydrolysis and total gastrodigenin with base-enzymatic hydrolysis followed by HPLC-FLD were put forward and successfully applied to evaluate the quality of 47 batches of G. elata from eight localities. Meanwhile, a systematic comparison of the novel strategy with the multiple markers and the Pharmacopeia method was performed. The results showed that the parishins category could be completely hydrolyzed to gastrodin by sodium hydroxide solution, and gastrodin could further utterly hydrolyze to gastrodigenin with β-d-glucosidase buffer solution. The contents of total gastrodin and gastrodigenin ranged from 1.311% to 2.034%, and total gastrodigenin from 0.748% to 1.120% at the eight localities. From the comparison, we can conclude that the two novel strategies can comprehensively reveal the characteristics of overall active ingredients in G. elata for quality control. The present study provides a feasible and credible strategy for the quality control of G. elata, suggesting a revision of the latest Chinese Pharmacopoeia or European Pharmacopoeia methods for the modernization of G. elata use. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 1369 KiB

Open AccessArticle

Chemical Constituents and Antioxidant, Anti-Inflammatory and Anti-Tumor Activities of Melilotus officinalis (Linn.) Pall

by Yu-Ting Liu¹, Pei-Han Gong¹, Feng-Qin Xiao¹, Shuai Shao¹, Da-Qing Zhao¹, Ming-Ming Yan^1,* and Xiu-Wei Yang^2,*

¹ Department of the Research and Development Center of Traditional Chinese Medicine and Biotechnology, Changchun University of Chinese Medicine, Changchun 130117, China

² State Key Laboratory of Natural and Biomimetic Drugs (Peking University), Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, China

Molecules 2018, 23(2), 271; https://doi.org/10.3390/molecules23020271 - 29 Jan 2018

Cited by 35 | Viewed by 6826

Abstract

Two new p-hydroxybenzoic acid glycosides, namely p-hydroxybenzoic acid-4-O-α-d-manopyranosyl-(1 → 3)-α-l-rhamnopyranoside (compound 1) and 4-O-α-l-rhamnopyran-osyl-(1 → 6)-α-d-manopyranosyl-(1 → 3)-α-l-rhamnopyranoside (compound 2), and seven known compounds, compound 3, [...] Read more.

Two new p-hydroxybenzoic acid glycosides, namely p-hydroxybenzoic acid-4-O-α-d-manopyranosyl-(1 → 3)-α-l-rhamnopyranoside (compound 1) and 4-O-α-l-rhamnopyran-osyl-(1 → 6)-α-d-manopyranosyl-(1 → 3)-α-l-rhamnopyranoside (compound 2), and seven known compounds, compound 3, 6, 7 (acid components), compound 8, 9 (flavonoids), compound 4 (a coumarin) and compound 5 (an alkaloid), were isolated from the 70% ethanol aqueous extract of the aerial parts of Melilotus officinalis (Linn.) Pall. The structures of all compounds were elucidated by use of extensive spectroscopic methods Infrared Spectroscopy (IR), High resolution electrospray ionization mass spectrometry (HR-ESI-MS), and ¹H and ¹³C-NMR). Sugar residues obtained after acid hydrolysis were identified by high-performance liquid chromatography (HPLC). The antioxidant activity of all the compounds was evaluated by 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS⁺) and 1,1-diphenyl-2-picrylhydrazyl (DPPH). The anti-inflammatory effects of the compounds were also evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. All compounds were shown to inhibit LPS-induced nitric oxide (NO) and prostaglandin E 2 (PGE 2) production by suppressing the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively, in LPS-stimulated RAW 264.7 cells. The inhibitory effect of all the compounds on MCF-7 cells was determined by Cell Counting Kit-8 (CCK-8) method. The results showed that compounds 1, 2, 7, 8, 9 exhibited better antioxidant activity compared to the other compounds. compounds 1–9 had different inhibitory effects on the release of NO, TNF-α and IL-6 in LPS-stimulated RAW264.7 cells by LPS, of which compound 7 was the most effective against inflammatory factors. compounds 1 and 2 have better antitumor activity compared to other compounds. Further research to elucidate the chemical composition and pharmacological effects of Melilotus officinalis (Linn.) Pall is of major importance towards the development and foundation of clinical application of the species. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 1862 KiB

Open AccessArticle

Evaluation of Melatonin Secretion and Metabolism Exponents in Patients with Ulcerative and Lymphocytic Colitis

by Cezary Chojnacki^1,*, Janusz Błasiak²

, Jakub Fichna³

, Jan Chojnacki¹ and Tomasz Popławski²

¹ Department of Clinical Nutrition and Gastroenterological Diagnostics, Medical University, 90-647 Lodz, Poland

² Department of Molecular Genetics, University of Lodz, 90-647 Lodz, Poland

³ Department of Biochemistry, Medical University of Lodz, 90-647 Lodz, Poland

Molecules 2018, 23(2), 272; https://doi.org/10.3390/molecules23020272 - 29 Jan 2018

Cited by 14 | Viewed by 4450

Abstract

Inflammatory bowel diseases, particularly ulcerative colitis (UC) and lymphocytic colitis (LC), affect many people. The role of melatonin in the pathogenesis of UC is precisely determined, whereas in LC it remains unknown. The aim of this study was to compare the expression of [...] Read more.

Inflammatory bowel diseases, particularly ulcerative colitis (UC) and lymphocytic colitis (LC), affect many people. The role of melatonin in the pathogenesis of UC is precisely determined, whereas in LC it remains unknown. The aim of this study was to compare the expression of the melatonin-synthesizing enzymes tryptophan hydroxylase (TPH1), arylalkylamine-N-acetyltransferase (AANAT), and N-acetylserotonin methyltransferase (ASMT) in the colonic mucosa and urinary excretion of 6-sulfatoxymelatonin in patients with ulcerative and lymphocytic colitis. The study included 30 healthy subjects (group C), 30 patients with severe ulcerative colitis (group UC), and 30 patients with lymphocytic colitis (group LC). The diagnosis was based on endoscopic, histological, and laboratory examinations. Biopsy specimens were collected from right, transverse, and left parts of the colon. The levels of mRNA expression, TPH1, AANAT, and ASMT were estimated in the colonic mucosa with RT-PCR. The urine concentration of aMT6s was determined by the photometric method. The expression of TPH1, AANAT, and ASMT in colonic mucosa in UC and LC patients was significantly higher than in healthy subjects. Significant differences were found in the urinary aMT6s excretion: group C—13.4 ± 4.8 µg/24 h, group UC—7.8 ± 2.6 µg/24 h (p < 0.01), group LC—19.2 ± 6.1 µg/24 h (p < 0.01). Moreover, a negative correlation was found between fecal calprotectin and MT6s—in patients with UC − r = −0.888 and with LC − r = −0.658. These results indicate that patients with UC and those with LC may display high levels of melatonin-synthesizing enzymes in their colonic mucosa, which could possibly be related to increased melatonin synthesis as an adaptive antioxidant activity. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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12 pages, 2921 KiB

Open AccessArticle

Preparation, Characterization and Catalytic Activity of Nickel Molybdate (NiMoO₄) Nanoparticles

by Hicham Oudghiri-Hassani^1,2,* and Fahd Al Wadaani¹

¹ Chemistry Department, College of Science, Taibah University, Almadinah 30002, Saudia Arabia

² Département Sciences de la nature, Cégep de Drummondville, 960 rue Saint-Georges, Drummondville, QC J2C 6A2, Canada

Molecules 2018, 23(2), 273; https://doi.org/10.3390/molecules23020273 - 29 Jan 2018

Cited by 40 | Viewed by 7881

Abstract

Nickel molybdate (NiMoO₄) nanoparticles were synthesized via calcination of an oxalate complex in static air at 500 °C. The oxalate complex was analyzed by thermal gravimetric analysis (TGA) and Fourier transform infrared spectroscopy (FTIR). The as-synthesized nickel molybdate was characterized by [...] Read more.

Nickel molybdate (NiMoO₄) nanoparticles were synthesized via calcination of an oxalate complex in static air at 500 °C. The oxalate complex was analyzed by thermal gravimetric analysis (TGA) and Fourier transform infrared spectroscopy (FTIR). The as-synthesized nickel molybdate was characterized by Brunauer–Emmett–Teller technique (BET), X-ray diffraction (XRD), and transmission electron microscopy (TEM) and its catalytic efficiency was tested in the reduction reaction of the three-nitrophenol isomers. The nickel molybdate displays a very high activity in the catalytic reduction of the nitro functional group to an amino. The reduction progress was controlled using Ultraviolet-Visible (UV-Vis) absorption. Full article

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19 pages, 2025 KiB

Open AccessArticle

Rapid Characterization and Identification of Non-Diterpenoid Constituents in Tinospora sinensis by HPLC-LTQ-Orbitrap MSⁿ

by Qi-Shu Jiao¹

, Lu-Lu Xu¹, Jia-Yu Zhang², Zi-Jian Wang², Yan-Yan Jiang¹ and Bin Liu^1,*

¹ School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China

² Beijing Research Institution of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China

Molecules 2018, 23(2), 274; https://doi.org/10.3390/molecules23020274 - 29 Jan 2018

Cited by 25 | Viewed by 10649

Abstract

Tinospora sinensis, a kind of Chinese folk medicine, has functions of harmonizing qi and blood, dredging the channels and collaterals, calming and soothing the nerves. In the present study, a method based on high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass [...] Read more.

Tinospora sinensis, a kind of Chinese folk medicine, has functions of harmonizing qi and blood, dredging the channels and collaterals, calming and soothing the nerves. In the present study, a method based on high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (HPLC-LTQ-Orbitrap) was developed for the systematical characterization of the non-diterpenoid constituents which possessed remarkable biological activities in T. sinensis, like anti-tumor, anti-inflammatory, hypoglycemic activity and immunomodulatory activity. Based on the accurate mass measurement (<5 ppm), retention times and MS fragmentation ions, 60 non-diterpenoid constituents were unambiguously or tentatively characterized from T. sinensis extract, including 27 alkaloids, 23 phenylpropanoids, seven sesquiterpenoids and three other constituents. Among them, 13 compounds were tentatively identified as new compounds. Finally, three of the non-diterpenoid constituents were purified and identified, which further confirmed the validity of the results. This study demonstrated that the HPLC-LTQ-Orbitrap MSⁿ platform was a useful and efficient analytical tool to screen and identify constituents in natural medicine. Full article

(This article belongs to the Collection Herbal Medicine Research)

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15 pages, 2966 KiB

Open AccessFeature PaperArticle

Lipase-Produced Hydroxytyrosyl Eicosapentaenoate is an Excellent Antioxidant for the Stabilization of Omega-3 Bulk Oils, Emulsions and Microcapsules

by Taiwo Olusesan Akanbi

and Colin James Barrow^*

Centre for Chemistry and Biotechnology, Deakin University, Locked Bag 20000, Geelong, VIC 3220, Australia

Molecules 2018, 23(2), 275; https://doi.org/10.3390/molecules23020275 - 29 Jan 2018

Cited by 39 | Viewed by 4747

Abstract

In this study, several lipophilic hydroxytyrosyl esters were prepared enzymatically using immobilized lipase from Candida antarctica B. Oxidation tests showed that these conjugates are excellent antioxidants in lipid-based matrices, with hydroxytyrosyl eicosapentaenoate showing the highest antioxidant activity. Hydroxytyrosyl eicosapentaenoate effectively stabilized bulk fish [...] Read more.

In this study, several lipophilic hydroxytyrosyl esters were prepared enzymatically using immobilized lipase from Candida antarctica B. Oxidation tests showed that these conjugates are excellent antioxidants in lipid-based matrices, with hydroxytyrosyl eicosapentaenoate showing the highest antioxidant activity. Hydroxytyrosyl eicosapentaenoate effectively stabilized bulk fish oil, fish-oil-in-water emulsions and microencapsulated fish oil. The stabilizing effect of this antioxidant may either be because it orients itself with the omega-3 fatty acids in the oil, thereby protecting them against oxidation, or because this unstable fatty acid can preferentially oxidise, thus providing an additional mechanism of antioxidant protection. Hydroxytyrosyl eicosapentaenoate itself was stable for one year when stored at −20 °C. Full article

(This article belongs to the Special Issue Lipases and Lipases Modification)

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10 pages, 1361 KiB

Open AccessArticle

Xylosylated Detoxification of the Rice Flavonoid Phytoalexin Sakuranetin by the Rice Sheath Blight Fungus Rhizoctonia solani

by Shun Katsumata, Hiroaki Toshima and Morifumi Hasegawa^*

College of Agriculture, Ibaraki University, 3-21-1 Chuo, Ami, Ibaraki 300-0393, Japan

Molecules 2018, 23(2), 276; https://doi.org/10.3390/molecules23020276 - 29 Jan 2018

Cited by 20 | Viewed by 6052

Abstract

Sakuranetin (1) is a rice flavanone-type phytoalexin. We have already reported that the metabolites from the detoxification of 1 by Pyricularia oryzae are naringenin (2) and sternbin. In this study, we investigated whether the rice sheath blight fungus Rhizoctonia [...] Read more.

Sakuranetin (1) is a rice flavanone-type phytoalexin. We have already reported that the metabolites from the detoxification of 1 by Pyricularia oryzae are naringenin (2) and sternbin. In this study, we investigated whether the rice sheath blight fungus Rhizoctonia solani, another major rice pathogen, can detoxify 1. The extract of R. solani suspension culture containing 1 was analyzed by LC-MS to identify the metabolites of 1. Three putative metabolites of 1 were detected in the extract from the R. solani suspension culture 12 h after the addition of 1, and they were identified as 2, sakuranetin-4′-O-β-d-xylopyranoside (3), and naringenin-7-O-β-d-xylopyranoside (4) by NMR, LC-MS/MS, and GC-MS analyses. The accumulation of 2, 3, and 4 reached their maximum levels 9–12 h after the addition of 1, whereas the content of 1 decreased to almost zero within 9 h. The antifungal activities of 3 and 4 against R. solani were negligible, and 2 showed weaker antifungal activity than 1. We concluded that 2, 3, and 4 are metabolites from the detoxification of 1 by R. solani. Xylosylation is a rare and efficient detoxification method for phytoalexins. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

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18 pages, 1738 KiB

Open AccessArticle

Yacon (Smallanthus sonchifolius Poepp. & Endl.) as a Novel Source of Health Promoting Compounds: Antioxidant Activity, Phytochemicals and Sugar Content in Flesh, Peel, and Whole Tubers of Seven Cultivars

by Forough Khajehei^1,*, Nikolaus Merkt², Wilhelm Claupein¹ and Simone Graeff-Hoenninger¹

¹ Department of Agronomy, Institute of Crop Science, University of Hohenheim, Fruwirthstr 23, 70599 Stuttgart, Germany

² Department of Quality of Plant Products, Institute of Crop Science, University of Hohenheim, Emil-Wolff-Strasse 23, 70599 Stuttgart, Germany

Molecules 2018, 23(2), 278; https://doi.org/10.3390/molecules23020278 - 29 Jan 2018

Cited by 30 | Viewed by 6689

Abstract

The aim of this study was to evaluate the quality characteristics of seven yacon (Smallanthus sonchifolius Poepp. and Endl.) cultivars (Cajamarca, Cusco, Early White, Late Red, Morado, New Zealand and Quinault) cultivated in the southwest of Germany. The following phyto/chemical traits were [...] Read more.

The aim of this study was to evaluate the quality characteristics of seven yacon (Smallanthus sonchifolius Poepp. and Endl.) cultivars (Cajamarca, Cusco, Early White, Late Red, Morado, New Zealand and Quinault) cultivated in the southwest of Germany. The following phyto/chemical traits were investigated in different yacon tuber parts (flesh, peel, and whole tubers): total dry matter, sugar content (fructose, glucose, and sucrose content), total phenolic content (TPC), total flavonoid content (TFC), 2,20-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, and Ferric reducing antioxidant power (FRAP). The results indicated a significant interaction between cultivar and tuber part on all of the examined traits (p < 0.0001). Of flesh and whole tuber, cv. Late Red, cv. Morado, and cv. Cajamarca had the highest TPC, TFC, DPPH radical scavenging activity, and FRAP. They also had relatively higher total sugar content. Cv. New Zealand had the lowest amount of sugars, TPC, TFC, DPPH radical scavenging activity, and FRAP, but the highest ABTS radical scavenging activity content in its flesh and whole tuber. Moreover, the results indicated that the peel of yacon tubers contained considerably high amounts of phytochemicals while possessing low sugar contents. Overall, this study provides a broad insight into the phyto/chemical content of yacon tubers from different cultivars, which can be used for further breeding programs, and the selection of proper cultivars for specific food product development. Full article

(This article belongs to the Special Issue The Antioxidant Capacities of Natural Products)

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10 pages, 2447 KiB

Open AccessCommunication

Curcumin Analog CH-5 Suppresses the Proliferation, Migration, and Invasion of the Human Gastric Cancer Cell Line HGC-27

by Gabriel Silva^1,†, Felipe Teixeira Lima^1,†, Viviane Seba^1,†, Ana Laura Mendes Lourenço^1,2, Thaise Graminha Lucas^1,2, Bianca Vieira De Andrade^1,2, Guilherme Silva Torrezan³, Carlos Roberto Polaquini³

, Marcelo Engracia Garcia², Lucélio Bernardes Couto², Reinaldo Bulgarelli Bestetti², Suzelei De Castro França¹, Ana Lúcia Fachin^1,2, Luis Octavio Regasini^3,* and Mozart Marins^1,2,*

¹ Biotechnology Unit, University of Ribeirão Preto, Av. Costábile Romano, 2201, Ribeirão Preto, SP CEP 14096-900, Brazil

² Medicine School, University of Ribeirão Preto, Av. Costábile Romano, 2201, Ribeirão Preto, SP CEP 14096-900, Brazil

³ Laboratory of Green and Medicinal Chemistry, Department of Chemistry and Environmental Sciences, Institute of Biosciences, Humanities and Exact Sciences, São Paulo State University (UNESP), São José do Rio Preto, SP CEP 15054-000, Brazil

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 279; https://doi.org/10.3390/molecules23020279 - 30 Jan 2018

Cited by 27 | Viewed by 4824

Abstract

Gastric cancer is one of the most frequent malignant tumors in the world. The majority of patients are diagnosed with metastatic gastric cancer, which has a low survival rate. These data reinforce the importance of studying the anticancer activity of new molecules with [...] Read more.

Gastric cancer is one of the most frequent malignant tumors in the world. The majority of patients are diagnosed with metastatic gastric cancer, which has a low survival rate. These data reinforce the importance of studying the anticancer activity of new molecules with the potential to suppress gastric cancer metastasis. Curcumin is a well-studied compound that has demonstrated anti-metastatic effects. Here we investigated if CH-5, a curcumin derivative compound, has anti-metastatic properties in the human gastric cancer cell line HGC-27. Firstly, we found that CH-5 decreased viability and induced apoptosis in HGC-27 cells in a dose-dependent manner. Additionally, CH-5 suppressed the migration and invasion of HGC-27 cells by downregulating the expression and collagenase activity of matrix metalloproteinase 2 in a dose-dependent manner. In conclusion, CH-5 showed anticancer activities, including the induction of apoptosis, and the suppression of migration and invasion in HGC-27 cells, suggesting that CH-5 can be a lead molecule for the development of anti-metastatic drugs for gastric cancer therapy. Full article

(This article belongs to the Section Natural Products Chemistry)

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19 pages, 6070 KiB

Open AccessArticle

Efficient OLEDs Fabricated by Solution Process Based on Carbazole and Thienopyrrolediones Derivatives

by Luis-Abraham Lozano-Hernández¹, José-Luis Maldonado^1,*

, Cesar Garcias-Morales^1,2

, Arian Espinosa Roa^1,†

, Oracio Barbosa-García¹, Mario Rodríguez¹ and Enrique Pérez-Gutiérrez³

¹ Research Group of Optical Properties of Materials (GPOM), Centro de Investigaciones en Óptica, 37000 León, Guanajuato, Mexico

² Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Autónoma de Coahuila, 25280 Saltillo, Coahuila, Mexico

³ CONACYT-Laboratorio de Polímeros, Centro de Química, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla (BUAP), Complejo de Ciencias, ICUAP, 72570 Puebla, Puebla, Mexico

^† Curret address: CONACYT-Centro de Investigación en Química Aplicada, Unidad Monterrey, Alianza Sur No. 204 Parque de Innovación e Investigación Tecnológica (PIIT), 66600 Apodaca, Nuevo León, Mexico.

Molecules 2018, 23(2), 280; https://doi.org/10.3390/molecules23020280 - 30 Jan 2018

Cited by 13 | Viewed by 6336

Abstract

Four low molecular weight compounds—three of them new, two of them with carbazole (Cz) as functional group and the other two with thienopyrroledione (TPD) group—were used as emitting materials in organic light emitting diodes (OLEDs). Devices were fabricated with the configuration ITO/PEDOT:PSS/emitting material/LiF/Al. [...] Read more.

Four low molecular weight compounds—three of them new, two of them with carbazole (Cz) as functional group and the other two with thienopyrroledione (TPD) group—were used as emitting materials in organic light emitting diodes (OLEDs). Devices were fabricated with the configuration ITO/PEDOT:PSS/emitting material/LiF/Al. The hole injector layer (HIL) and the emitting sheet were deposited by spin coating; LiF and Al were thermally evaporated. OLEDs based on carbazole derivatives show luminances up to 4130 cd/m², large current efficiencies about 20 cd/A and, cautiously, a very impressive External Quantum Efficiency (EQE) up to 9.5%, with electroluminescence peaks located around 490 nm (greenish blue region). Whereas, devices manufactured with TPD derivatives, present luminance up to 1729 cd/m², current efficiencies about 4.5 cd/A and EQE of 1.5%. These results are very competitive regarding previous reported materials/devices. Full article

(This article belongs to the Section Organic Chemistry)

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14 pages, 2546 KiB

Open AccessArticle

Preliminary Characterization, Antioxidant and Hepatoprotective Activities of Polysaccharides from Taishan Pinus massoniana Pollen

by Changming Zhou^1,†, Shaojie Yin^1,2,†, Zhongfang Yu¹, Yuxiang Feng¹, Kai Wei¹, Weiming Ma¹, Lijiang Ge¹, Zhengui Yan^1,3,* and Ruiliang Zhu^1,3,*

¹ College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an 271018, China

² College of Veterinary Medicine, Yangzhou University, 12 East Wenhui Road, Yangzhou 225009, China

³ Research Center for Animal Disease Control Engineering Shandong Province, Shandong Agricultural University, Tai’an 271018, China

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 281; https://doi.org/10.3390/molecules23020281 - 30 Jan 2018

Cited by 19 | Viewed by 4876

Abstract

The objectives of the present study were to characterize the chemical composition, antioxidant activity and hepatoprotective effect of the polysaccharides from Taishan Pinus massoniana pollen (TPPPS). HPLC analysis showed that TPPPS was an acidic heteropolysaccharide with glucose and arabinose as the main component [...] Read more.

The objectives of the present study were to characterize the chemical composition, antioxidant activity and hepatoprotective effect of the polysaccharides from Taishan Pinus massoniana pollen (TPPPS). HPLC analysis showed that TPPPS was an acidic heteropolysaccharide with glucose and arabinose as the main component monosaccharides (79.6%, molar percentage). Fourier transform-infrared spectroscopy (FT-IR) analysis indicated that the spectra of TPPPS displayed infrared absorption peaks characteristic of polysaccharides. In in vitro assays TPPPS exhibited different degrees of dose-dependent antioxidant activities , and this was further verified by suppression of CCl₄-induced oxidative stress in the liver with three tested doses of TPPPS (100, 200, and 400 mg/kg bw) in rats. Pretreatment with TPPPS significantly decreased the levels of alanine aminotransferase (AST), aspartate aminotransferase (ALT), alkaline phosphatase (ALP), lactic dehydrogenase (LDH) and malondialdehyde (MDA) against CCl₄ injuries, and elevated the activities of superoxide dismutase (SOD) as well as glutathione peroxidase (GSH-Px). Histopathological observation further confirmed that TPPPS could protect the liver tissues from CCl₄-induced histological alternation. These results suggest that TPPPS has strong antioxidant activities and significant protective effect against acute hepatotoxicity induced by CCl₄. The hepatoprotective effect may partly be related to its free radical scavenging effect, increasing antioxidant activity and inhibiting lipid peroxidation. Full article

(This article belongs to the Special Issue Polysaccharide-based Materials)

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8 pages, 1591 KiB

Open AccessCommunication

Chloro-1,4-dimethyl-9H-carbazole Derivatives Displaying Anti-HIV Activity

by Carmela Saturnino¹, Fedora Grande^2,*

, Stefano Aquaro^2,*, Anna Caruso², Domenico Iacopetta²

, Maria Grazia Bonomo¹, Pasquale Longo³, Dominique Schols⁴

and Maria Stefania Sinicropi²

¹ Department of Science, University of Basilicata, 85100 Potenza, Italy

² Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy

³ Department of Chemistry and Biology, University of Salerno, 84084 Fisciano, Italy

⁴ KU Leuven, Rega Institute for Medical Research, Herestraat 49, B-3000 Leuven, Belgium

Molecules 2018, 23(2), 286; https://doi.org/10.3390/molecules23020286 - 30 Jan 2018

Cited by 21 | Viewed by 3741

Abstract

Background: Despite the progress achieved by anti-retroviral drug research in the last decades, the discovery of novel compounds endowed with selective antiviral activity and reduced side effects is still a necessity. At present, the most urgent requirement includes the improvement of HIV (Human [...] Read more.

Background: Despite the progress achieved by anti-retroviral drug research in the last decades, the discovery of novel compounds endowed with selective antiviral activity and reduced side effects is still a necessity. At present, the most urgent requirement includes the improvement of HIV (Human Immunodeficiency Virus) prevention and sexual transmission and the development of new drugs to treat the chronic lifelong infection. Methods: Six chloro-1,4-dimethyl-9H-carbazoles (2a,b–4a,b) have been prepared following opportunely modified known chemical procedures and tested in luciferase and Escherichia coli β-galactosidase expressing CD4⁺, CXCR4⁺, CCR5⁺ TZM-bl cells. Results and Conclusion: a preliminary biological investigation on the synthesized small series of chloro-1,4-dimethyl-9H-carbazoles has been carried out. Among all tested compounds, a nitro-derivative (3b) showed the most interesting profile representing a suitable lead for the development of novel anti-HIV drugs. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 3429 KiB

Open AccessArticle

The Effect of Methyl-β-cyclodextrin on Apoptosis, Proliferative Activity, and Oxidative Stress in Adipose-Derived Mesenchymal Stromal Cells of Horses Suffering from Metabolic Syndrome (EMS)

by Joanna Szydlarska¹, Christine Weiss¹ and Krzysztof Marycz^1,2,*

¹ Department of Experimental Biology and Electron Microscope Facility, The Faculty of Biology and Animal Science, Wroclaw University of Environmental and Life Sciences, 50-631 Wroclaw, Poland

² Wroclaw Research Centre EIT+, 54-066 Wroclaw, Poland

Molecules 2018, 23(2), 287; https://doi.org/10.3390/molecules23020287 - 30 Jan 2018

Cited by 5 | Viewed by 4775

Abstract

Methyl-β-cyclodextrin (MβCD) is a cyclic oligosaccharide, commonly used as a pharmacological agent to deplete membrane cholesterol. In this study, we examined the effect of MβCD on adipose-derived mesenchymal stromal cells (ASCs) isolated form healthy horses (ASC_CTRL) and from horses suffering from [...] Read more.

Methyl-β-cyclodextrin (MβCD) is a cyclic oligosaccharide, commonly used as a pharmacological agent to deplete membrane cholesterol. In this study, we examined the effect of MβCD on adipose-derived mesenchymal stromal cells (ASCs) isolated form healthy horses (ASC_CTRL) and from horses suffering from metabolic syndrome (ASC_EMS). We investigated the changes in the mRNA levels of the glucose transporter 4 (GLUT4) and found that MβCD application may lead to a significant improvement in glucose transport in ASC_EMS. We also showed that MβCD treatment affected GLUT4 upregulation in an insulin-independent manner via an NO-dependent signaling pathway. Furthermore, the analysis of superoxide dismutase activity (SOD) and reactive oxygen species (ROS) levels showed that MβCD treatment was associated with an increased antioxidant capacity in ASC_EMS. Moreover, we indicated that methyl-β-cyclodextrin treatment did not cause a dysfunction of the endoplasmic reticulum and lysosomes. Thereby, we propose the possibility of improving the functionality of ASC_EMS by increasing their metabolic stability. Full article

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12 pages, 2832 KiB

Open AccessArticle

2-(2-Phenylethyl)-4H-chromen-4-one Derivatives from the Resinous Wood of Aquilaria sinensis with Anti-Inflammatory Effects in LPS-Induced Macrophages

by Sin-Ling Wang¹, Yun-Chen Tsai²

, Shu-Ling Fu^2,†, Ming-Jen Cheng³, Mei-Ing Chung^1,*,† and Jih-Jung Chen^4,5,*

¹ School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan

² Institute of Traditional Medicine, National Yang-Ming University, Taipei 112, Taiwan

³ Bioresource Collection and Research Center (BCRC), Food Industry Research and Development Institute (FIRDI), Hsinchu 300, Taiwan

⁴ Faculty of Pharmacy, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan

⁵ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 289; https://doi.org/10.3390/molecules23020289 - 30 Jan 2018

Cited by 42 | Viewed by 5194

Abstract

The resinous wood of Aquilaria sinensis, known as agarwood (Chen Xiang in Chinese), is traditionally used for the treatment of abdominal pain, vomiting, circulatory disorders, and dyspnea. Four new 2-(2-phenylethyl)-4H-chromen-4-one derivatives, namely 7-methoxy-2-[2-(4′-hydroxy-phenyl)ethyl]chromone (1), 7-hydroxy-2-[2-(4′-methoxyphenyl)ethyl]chromone (2 [...] Read more.

The resinous wood of Aquilaria sinensis, known as agarwood (Chen Xiang in Chinese), is traditionally used for the treatment of abdominal pain, vomiting, circulatory disorders, and dyspnea. Four new 2-(2-phenylethyl)-4H-chromen-4-one derivatives, namely 7-methoxy-2-[2-(4′-hydroxy-phenyl)ethyl]chromone (1), 7-hydroxy-2-[2-(4′-methoxyphenyl)ethyl]chromone (2), 5,6-dihydroxy- 2-[2-(3′-hydroxy-4′-methoxyphenyl)ethyl]chromone (3), and 6-hydroxy-5-methoxy-2-(2-phenyl-ethyl)chromone (4), have been isolated from the resinous wood of A. sinensis, together with nine known compounds. The structures of these compounds were determined through spectroscopic and MS analyses. Among the isolated compounds, neopetasan, 7-methoxy-2-(2-phenylethyl)-chromone, 6,7-dimethoxy-2-(2-phenylethyl)chromone, and 6,7-dimethoxy-2-[2-(4′-methoxy-phenyl)ethyl]chromone inhibited NF-κB activation in LPS-stimulated RAW 264.7 macrophages with relative luciferase activity values of 0.55 ± 0.09, 0.54 ± 0.03, 0.31 ± 0.05, and 0.38 ± 0.14, respectively, versus that of vehicle control (1.03 ± 0.02). In addition, 5,6-dihydroxy-2-[2-(3′-hydroxy-4′-methoxyphenyl)ethyl]chromone, 7-methoxy-2-(2-phenylethyl)chromone, 7-dimethoxy-2-(2-phenylethyl)chromone, and 6,7-dimethoxy-2-[2-(4′-methoxyphenyl)ethyl]chromone could suppress LPS-induced NO production in RAW 264.7 cells and did not induce cytotoxicity against RAW 264.7 cells after 24-h treatment. Full article

(This article belongs to the Section Natural Products Chemistry)

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17 pages, 3176 KiB

Open AccessFeature PaperArticle

Enzymatic Synthesis of Amino Acids Endcapped Polycaprolactone: A Green Route Towards Functional Polyesters

by Stéphane W. Duchiron¹

, Eric Pollet^1,*

, Sébastien Givry²

and Luc Avérous^1,*

¹ BioTeam/ICPEES-ECPM, UMR CNRS 7515, Université de Strasbourg, 25 rue Becquerel, 67087 Strasbourg CEDEX 2, France

² J. SOUFFLET S. A., Centre de Recherche et d’Innovation Soufflet—Division Biotechnologies, Quai du Général Sarail, 10402 Nogent sur Seine CEDEX 2, France

Molecules 2018, 23(2), 290; https://doi.org/10.3390/molecules23020290 - 30 Jan 2018

Cited by 11 | Viewed by 6127

Abstract

ε-caprolactone (CL) has been enzymatically polymerized using α-amino acids based on sulfur (methionine and cysteine) as (co-)initiators and immobilized lipase B of Candida antarctica (CALB) as biocatalyst. In-depth characterizations allowed determining the corresponding involved mechanisms and the polymers thermal properties. Two synthetic strategies [...] Read more.

ε-caprolactone (CL) has been enzymatically polymerized using α-amino acids based on sulfur (methionine and cysteine) as (co-)initiators and immobilized lipase B of Candida antarctica (CALB) as biocatalyst. In-depth characterizations allowed determining the corresponding involved mechanisms and the polymers thermal properties. Two synthetic strategies were tested, a first one with direct polymerization of CL with the native amino acids and a second one involving the use of an amino acid with protected functional groups. The first route showed that mainly polycaprolactone (PCL) homopolymer could be obtained and highlighted the lack of reactivity of the unmodified amino acids due to poor solubility and affinity with the lipase active site. The second strategy based on protected cysteine showed higher monomer conversion, with the amino acids acting as (co-)initiators, but their insertion along the PCL chains remained limited to chain endcapping. These results thus showed the possibility to synthesize enzymatically polycaprolactone-based chains bearing amino acids units. Such cysteine endcapped PCL materials could then find application in the biomedical field. Indeed, subsequent functionalization of these polyesters with drugs or bioactive molecules can be obtained, by derivatization of the amino acids, after removal of the protecting group. Full article

(This article belongs to the Special Issue Natural Polymers and Biopolymers)

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12 pages, 1640 KiB

Open AccessArticle

A Lateral Flow Strip Based Aptasensor for Detection of Ochratoxin A in Corn Samples

by Guilan Zhang¹, Chao Zhu¹, Yafei Huang^1,2, Jiao Yan^1,2 and Ailiang Chen^1,*

¹ Key Laboratory of Agro-Product Quality and Safety, Institute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China

² College of Food Science and Technology, Hainan University, Haikou 570228, China

Molecules 2018, 23(2), 291; https://doi.org/10.3390/molecules23020291 - 31 Jan 2018

Cited by 47 | Viewed by 6507

Abstract

Ochratoxin A (OTA) is a mycotoxin identified as a contaminant in grains and wine throughout the world, and convenient, rapid and sensitive detection methods for OTA have been a long-felt need for food safety monitoring. Herein, we presented a new competitive format based [...] Read more.

Ochratoxin A (OTA) is a mycotoxin identified as a contaminant in grains and wine throughout the world, and convenient, rapid and sensitive detection methods for OTA have been a long-felt need for food safety monitoring. Herein, we presented a new competitive format based lateral flow strip fluorescent aptasensor for one-step determination of OTA in corn samples. Briefly, biotin-cDNA was immobilized on the surface of a nitrocellulose filter on the test line. Without OTA, Cy5-labeled aptamer combined with complementary strands formed a stable double helix. In the presence of OTA, however, the Cy5-aptamer/OTA complexes were generated, and therefore less free aptamer was captured in the test zone, leading to an obvious decrease in fluorescent signals on the test line. The test strip showed an excellent linear relationship in the range from 1 ng·mL⁻¹ to 1000 ng·mL⁻¹ with the LOD of 0.40 ng·mL⁻¹, IC₁₅ value of 3.46 ng·mL⁻¹ and recoveries from 96.4% to 104.67% in spiked corn samples. Thus, the strip sensor developed in this study is an acceptable alternative for rapid detection of the OTA level in grain samples. Full article

(This article belongs to the Special Issue Nucleic Acid Aptamers)

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13 pages, 1085 KiB

Open AccessArticle

Biodiversity within Melissa officinalis: Variability of Bioactive Compounds in a Cultivated Collection

by Remigius Chizzola^1,*, Ulrike Lohwasser²

and Chlodwig Franz¹

¹ Institute of Animal Nutrition and Functional Plant Compounds, University of Veterinary Medicine Vienna, Veterinaerplatz 1, 1210 Vienna, Austria

² Leibniz Institute of Plant Genetics and Crop Research (IPK), Corrensstraße 3, Seeland, OT 06466 Gatersleben, Germany

Molecules 2018, 23(2), 294; https://doi.org/10.3390/molecules23020294 - 31 Jan 2018

Cited by 27 | Viewed by 6059

Abstract

Phytochemical characters were evaluated in a five-year-old lemon balm collection consisting of 15 and 13 subspecies officinalis and altissima accessions, respectively. Stems were lower in essential oil than leaves. First cut leaves (June) gave more oil than those of the second cut (August). [...] Read more.

Phytochemical characters were evaluated in a five-year-old lemon balm collection consisting of 15 and 13 subspecies officinalis and altissima accessions, respectively. Stems were lower in essential oil than leaves. First cut leaves (June) gave more oil than those of the second cut (August). Subspecies officinalis plants had leaf oils rich in geranial, neral and citronellal in various proportions in the first cut. However, in the second cut the oils from all accessions appeared very similar with 80–90% geranial plus neral. Leaf oils of subsp. altissima contained sesquiterpenes (β-caryophyllene, caryophyllene oxide, germacrene D) and also further monoterpenes in the second cut. Leaves had higher rosmarinic acid (RA) contents than stems. More RA was in subsp. officinalis than subsp. altissima leaves. First cut leaves were richer in RA than those from second cut. Total phenolics and antioxidant parameters showed that lemon balm is a valuable source of plant antioxidants. Full article

(This article belongs to the Section Chemical Biology)

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13 pages, 1719 KiB

Open AccessArticle

Synthesis and In Vitro Antiproliferative Activity of New 1-Phenyl-3-(4-(pyridin-3-yl)phenyl)urea Scaffold-Based Compounds

by Mohammad M. Al-Sanea^1,*

, Mohammed Safwan Ali Khan^2,3,4,*

, Ahmed Z. Abdelazem⁵, So Ha Lee⁶, Pooi Ling Mok^4,7,*, Mohammed Gamal^1,8

, Mohamed E. Shaker^2,9, Muhammad Afzal², Bahaa G. M. Youssif^1,10

and Nesreen Nabil Omar¹¹

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, Aljouf University, Sakaka 2014, Aljouf Province, Saudi Arabia

² Department of Pharmacology, College of Pharmacy, Aljouf University, Sakaka 2014, Aljouf Province, Saudi Arabia

³ Department of Pharmacology, Anwarul Uloom College of Pharmacy, Jawaharlal Nehru Technological University, Hyderabad 500001, Telangana, India

⁴ Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia

⁵ Department of Biotechnology & Life Sciences, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef 62574, Egypt

⁶ Chemical Kinomics Research Center, Korea Institute of Science and Technology, Seoul 136-791, Korea

⁷ Genetics and Regenerative Medicine Research Centre, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia

⁸ Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Beni-Suef University, Alshaheed Shehata Ahmed Hegazy St., Beni-Suef 62574, Egypt

⁹ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt

¹⁰ Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt

¹¹ Department of Biochemistry, Faculty of Pharmacy, Modern University for Technology & Information, 11571 Cairo, Egypt

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Molecules 2018, 23(2), 297; https://doi.org/10.3390/molecules23020297 - 31 Jan 2018

Cited by 9 | Viewed by 3766

Abstract

A new series of 1-phenyl-3-(4-(pyridin-3-yl)phenyl)urea derivatives were synthesized and subjected to in vitro antiproliferative screening against National Cancer Institute (NCI)-60 human cancer cell lines of nine different cancer types. Fourteen compounds 5a–n were synthesized with three different solvent exposure moieties (4-hydroxylmethylpiperidinyl [...] Read more.

A new series of 1-phenyl-3-(4-(pyridin-3-yl)phenyl)urea derivatives were synthesized and subjected to in vitro antiproliferative screening against National Cancer Institute (NCI)-60 human cancer cell lines of nine different cancer types. Fourteen compounds 5a–n were synthesized with three different solvent exposure moieties (4-hydroxylmethylpiperidinyl and trimethoxyphenyloxy and 4-hydroxyethylpiperazine) attached to the core structure. Substituents with different π and σ values were added on the terminal phenyl group. Compounds 5a–e with a 4-hydroxymethylpiperidine moiety showed broad-spectrum antiproliferative activity with higher mean percentage inhibition values over the 60-cell line panel at 10 µM concentration. Compound 5a elicited lethal rather than inhibition effects on SK-MEL-5 melanoma cell line, 786-0, A498, RXF 393 renal cancer cell lines, and MDA-MB-468 breast cancer cell line. Two compounds, 5a and 5d showed promising mean growth inhibitions and thus were further tested at five-dose mode to determine median inhibitory concentration (IC₅₀) values. The data revealed that urea compounds 5a and 5d are the most active derivatives, with significant efficacies and superior potencies than paclitaxel in 21 different cancer cell lines belonging particularly to renal cancer and melanoma cell lines. Moreover, 5a and 5d had superior potencies than gefitinib in 38 and 34 cancer cell lines, respectively, particularly colon cancer, breast cancer and melanoma cell lines. Full article

(This article belongs to the Section Medicinal Chemistry)

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10 pages, 1126 KiB

Open AccessArticle

Highly Efficient One-Pot Synthesis of COS-Based Block Copolymers by Using Organic Lewis Pairs

by Jia-Liang Yang, Xiao-Han Cao, Cheng-Jian Zhang, Hai-Lin Wu and Xing-Hong Zhang^*

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China

Molecules 2018, 23(2), 298; https://doi.org/10.3390/molecules23020298 - 31 Jan 2018

Cited by 21 | Viewed by 4077

Abstract

A one-pot synthesis of block copolymer with regioregular poly(monothiocarbonate) block is described via metal-free catalysis. Lewis bases such as guanidine, quaternary onium salts, and Lewis acid triethyl borane (TEB) were equivalently combined and used as the catalysts. By using polyethylene glycol (PEG) as [...] Read more.

A one-pot synthesis of block copolymer with regioregular poly(monothiocarbonate) block is described via metal-free catalysis. Lewis bases such as guanidine, quaternary onium salts, and Lewis acid triethyl borane (TEB) were equivalently combined and used as the catalysts. By using polyethylene glycol (PEG) as the macromolecular chain transfer agent (CTA), narrow polydispersity block copolymers were obtained from the copolymerization of carbonyl sulfide (COS) and propylene oxide (PO). The block copolymers had a poly(monothiocarbonate) block with perfect alternating degree and regioregularity. Unexpectedly, the addition of CTA to COS/PO copolymerization system could dramatically improve the turnover frequency (TOF) of PO (up to 240 h⁻¹), higher than that of the copolymerization without CTA. In addition, the conversion of CTA could be up to 100% in most cases, as revealed by ¹H NMR spectra. Of consequence, the number-average molecular weights (M_ns) of the resultant block copolymers could be regulated by varying the feed ratio of CTA to PO. Oxygen-sulfur exchange reaction (O/S ER), which can generate randomly distributed thiocarbonate and carbonate units, was effectively suppressed in all of the cases in the presence of CTA, even at 80 °C. This work presents a versatile method for synthesizing sulfur-containing block copolymers through a metal-free route, providing an array of new block copolymers. Full article

(This article belongs to the Special Issue Lewis Pair Polymerization for New Reactivity and Structure in Polymer Synthesis)

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12 pages, 8957 KiB

Open AccessArticle

Terretonin N: A New Meroterpenoid from Nocardiopsis sp.

by Abdelaaty Hamed^1,2

, Ahmed S. Abdel-Razek^1,3

, Marcel Frese¹, Hans Georg Stammler⁴, Atef F. El-Haddad², Tarek M. A. Ibrahim², Norbert Sewald^1,*

and Mohamed Shaaban^1,5,*

¹ Organic and Bioorganic Chemistry, Faculty of Chemistry, Bielefeld University, D-33501 Bielefeld, Germany

² Department of Chemistry, Faculty of Science, Al-Azhar University, Nasr City-Cairo 11884, Egypt

³ Department of Microbial Chemistry, Division of Genetic Engineering and Biotechnology Research, National Research Centre, El-Buhouth St. 33, Dokki-Cairo 12622, Egypt

⁴ Department of Chemistry, Inorganic and Structural Chemistry, Bielefeld University, D-33501 Bielefeld, Germany

⁵ Department of Chemistry of Natural Compounds, Pharmaceutical and Drug Industries Research Division, National Research Centre, El-Buhouth St. 33, Dokki-Cairo 12622, Egypt

Molecules 2018, 23(2), 299; https://doi.org/10.3390/molecules23020299 - 31 Jan 2018

Cited by 32 | Viewed by 5039

Abstract

Terretonin N (1), a new highly oxygenated and unique tetracyclic 6-hydroxymeroterpenoid, was isolated together with seven known compounds from the ethyl acetate extract of a solid-state fermented culture of Nocardiopsis sp. Their structures were elucidated by spectroscopic analysis. The structure and [...] Read more.

Terretonin N (1), a new highly oxygenated and unique tetracyclic 6-hydroxymeroterpenoid, was isolated together with seven known compounds from the ethyl acetate extract of a solid-state fermented culture of Nocardiopsis sp. Their structures were elucidated by spectroscopic analysis. The structure and absolute configuration of 1 were unambiguously determined by X-ray crystallography. The isolation and taxonomic characterization of Nocardiopsis sp. is reported. The antimicrobial activity and cytotoxicity of the strain extract and compound 1 were studied using different microorganisms and a cervix carcinoma cell line, respectively. Full article

(This article belongs to the Section Natural Products Chemistry)

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7 pages, 739 KiB

Open AccessArticle

Spiroketones and a Biphenyl Analog from Stems and Leaves of Larrea nitida and Their Inhibitory Activity against IL-6 Production

by Jongmin Ahn^1,†, Yihua Pei^2,†, Hee-Sung Chae², Seong-Hwan Kim¹, Young-Mi Kim², Young Hee Choi²

, Joongku Lee³, Minsun Chang⁴, Yun Seon Song⁵, Roberto Rodriguez⁶, Dong-Chan Oh¹, Jinwoong Kim¹, Sangho Choi⁷, Sang Hoon Joo⁸ and Young-Won Chin^2,*

¹ College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea

² College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Gyeonggi-do 10326, Korea

³ Department of Environment and Forest Resources, College of Agriculture and Life Sciences, Chungnam National University, Daejeon 34134, Korea

⁴ Department of Biological Sciences, College of Science, Sookmyung Women’s University, Seoul 04310, Korea

⁵ College of Pharmacy, Sookmyung Women's University, Seoul 04310, Korea

⁶ Department of Botany, University of Concepcion, Casilla 160C, Concepcion 4080871, Chile

⁷ International Biological Material Research Center, KRIBB, Daejeon 34141, Korea

⁸ College of Pharmacy, Daegu Catholic University, Gyeongbuk 38430, Korea

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 302; https://doi.org/10.3390/molecules23020302 - 31 Jan 2018

Cited by 2 | Viewed by 3239

Abstract

Bioactivity-guided fractionation for the stems of leaves of Larrea nitida Cav., using interleukin-6 (IL-6) inhibitory assay in human mast cells (HMC-1), led to the isolation of three new compounds with an unprecedented skeleton in nature (1–3) and three known [...] Read more.

Bioactivity-guided fractionation for the stems of leaves of Larrea nitida Cav., using interleukin-6 (IL-6) inhibitory assay in human mast cells (HMC-1), led to the isolation of three new compounds with an unprecedented skeleton in nature (1–3) and three known compounds (4–6). Their structures were elucidated through extensive spectroscopic analysis. The three new compounds were elucidated as two new spiroketones, nitidaones A (1), and B (2) and one new biphenyl analog, nitidaol (3). The known compounds were identified as nordihydroguaiaretic acid (4), 7,3′,4′-tri-O-methylquercetin (5) and ayanin (6). All the isolates were tested for their inhibitory activity against IL-6 production in HMC-1 cells. Of them, compounds 1, 3–6 showed potent anti-inflammatory activity, with IC₅₀ values of 12.8, 17.5, 14.9, 22.9, and 17.8 µM, respectively. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 2858 KiB

Open AccessArticle

Optimization of the Preparation Conditions of Borneol-Modified Ginkgolide Liposomes by Response Surface Methodology and Study of Their Blood Brain Barrier Permeability

by Zhiyang Lv^1,2,3,4, Yuwei Yang², Jie Wang², Jing Chen^1,2, Junsong Li¹ and Liuqing Di^1,3,4,*

¹ College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China

² Hanlin College, Nanjing University of Chinese Medicine, Taizhou 225300, China

³ Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing 210046, China

⁴ Nanjing Engineering Research Center for Industrialization of Chinese Medicine Pellets, Nanjing 210046, China

Molecules 2018, 23(2), 303; https://doi.org/10.3390/molecules23020303 - 31 Jan 2018

Cited by 29 | Viewed by 4624

Abstract

Ginkgolides (GG), containing ginkgolide A (GA), ginkgolide B (GB) and ginkgolide C (GC), are mainly prescribed for ischemic stroke and cerebral infarction. However, the ginkgolides can hardly pass the blood-brain barrier (BBB) into the brain. The purpose of this study was to prepare [...] Read more.

Ginkgolides (GG), containing ginkgolide A (GA), ginkgolide B (GB) and ginkgolide C (GC), are mainly prescribed for ischemic stroke and cerebral infarction. However, the ginkgolides can hardly pass the blood-brain barrier (BBB) into the brain. The purpose of this study was to prepare borneol-modified ginkgolides liposomes (GGB-LPs) to study whether borneol could enhance the transport of ginkgolides across the BBB. The preparation conditions of GGB-LPs were optimized by a response surface-central composite design. Also, pharmacokinetics and biodistribution studies of GGB-LPs were conducted using UPLC-MS. The optimal preparation conditions for GGB-LP were as follows: ratio of lipid to drug (w/w) was 9:1, ratio of phospholipid to cholesterol (w/w) was 7:1, and hydrate volume was 17.5 mL. Under these conditions, the GGB-LP yield was 89.73 ± 3.45%. With GGB-LPs, borneol significantly promoted the transport of ginkgolide across the BBB. The pharmacokinetic parameters of GGB-LP were significantly improved too, with T_max of 15 min and a high drug concentration of 3.39 μg/g in brain. Additionally, the drug targeting index and relative uptake rate of GGB-LP was increased. Borneol-modified ginkgolide liposomes can thus potentially be used to improve the BBB permeability of gingkolide formulations. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 11465 KiB

Open AccessArticle

A Cyclic Altered Peptide Analogue Based on Myelin Basic Protein 87–99 Provides Lasting Prophylactic and Therapeutic Protection Against Acute Experimental Autoimmune Encephalomyelitis

by Mary Emmanouil¹, Vivian Tseveleki¹, Iro Triantafyllakou², Agathi Nteli², Theodore Tselios^2,* and Lesley Probert^1,*

¹ Laboratory of Molecular Genetics, Hellenic Pasteur Institute, 127 Vasilissis Sophias Ave., 11521 Athens, Greece

² Department of Chemistry, University of Patras, 26504 Patras, Greece

Molecules 2018, 23(2), 304; https://doi.org/10.3390/molecules23020304 - 31 Jan 2018

Cited by 6 | Viewed by 3881

Abstract

In this report, amide-linked cyclic peptide analogues of the 87–99 myelin basic protein (MBP) epitope, a candidate autoantigen in multiple sclerosis (MS), are tested for therapeutic efficacy in experimental autoimmune encephalomyelitis (EAE). Cyclic altered peptide analogues of MBP_87–99 with substitutions at positions [...] Read more.

In this report, amide-linked cyclic peptide analogues of the 87–99 myelin basic protein (MBP) epitope, a candidate autoantigen in multiple sclerosis (MS), are tested for therapeutic efficacy in experimental autoimmune encephalomyelitis (EAE). Cyclic altered peptide analogues of MBP_87–99 with substitutions at positions 91 and/or 96 were tested for protective effects when administered using prophylactic or early therapeutic protocols in MBP_72–85-induced EAE in Lewis rats. The Lys⁹¹ and Pro⁹⁶ of MBP_87–99 are crucial T-cell receptor (TCR) anchors and participate in the formation of trimolecular complex between the TCR-antigen (peptide)-MHC (major histocompability complex) for the stimulation of encephalitogenic T cells that are necessary for EAE induction and are implicated in MS. The cyclic peptides were synthesized using Solid Phase Peptide Synthesis (SPPS) applied on the 9-fluorenylmethyloxycarboxyl/tert-butyl Fmoc/tBu methodology and combined with the 2-chlorotrityl chloride resin (CLTR-Cl). Cyclo(91–99)[Ala⁹⁶]MBP_87–99, cyclo(87–99)[Ala^91,96]MBP_87–99 and cyclo(87–99)[Arg⁹¹, Ala⁹⁶]MBP_87–99, but not wild-type linear MBP_87–99, strongly inhibited MBP_72–85-induced EAE in Lewis rats when administered using prophylactic and early therapeutic vaccination protocols. In particular, cyclo(87–99)[Arg⁹¹, Ala⁹⁶]MBP_87–99 was highly effective in preventing the onset and development of clinical symptoms and spinal cord pathology and providing lasting protection against EAE induction. Full article

(This article belongs to the Special Issue Peptide Therapeutics)

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8 pages, 2833 KiB

Open AccessFeature PaperArticle

Exploring Alternative Radiolabeling Strategies for Sialic Acid-Binding Immunoglobulin-Like Lectin 9 Peptide: [⁶⁸Ga]Ga- and [¹⁸F]AlF-NOTA-Siglec-9

by Olli Moisio¹, Riikka Siitonen¹, Heidi Liljenbäck^1,2, Elli Suomela¹, Sirpa Jalkanen³, Xiang-Guo Li^1,4

and Anne Roivainen^1,2,5,*

¹ Turku PET Centre, University of Turku, FI-20521 Turku, Finland

² Turku Center for Disease Modeling, University of Turku, FI-20520 Turku, Finland

³ MediCity Research Laboratory, University of Turku, FI-20520 Turku, Finland

⁴ Turku PET Centre, Åbo Akademi University, FI-20521 Turku, Finland

⁵ Turku PET Centre, Turku University Hospital, FI-20521 Turku, Finland

Molecules 2018, 23(2), 305; https://doi.org/10.3390/molecules23020305 - 31 Jan 2018

Cited by 6 | Viewed by 4203

Abstract

Amino acid residues 283–297 from sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) form a cyclic peptide ligand targeting vascular adhesion protein-1 (VAP-1). VAP-1 is associated with the transfer of leukocytes from blood to tissues upon inflammation. Therefore, analogs of Siglec-9 peptide are good candidates [...] Read more.

Amino acid residues 283–297 from sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) form a cyclic peptide ligand targeting vascular adhesion protein-1 (VAP-1). VAP-1 is associated with the transfer of leukocytes from blood to tissues upon inflammation. Therefore, analogs of Siglec-9 peptide are good candidates for visualizing inflammation non-invasively using positron emission tomography (PET). Gallium-68-labeled 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA)-conjugated Siglec-9 has been evaluated extensively for this purpose. Here, we explored two alternative strategies for radiolabeling Siglec-9 peptide using a 1,4,7-triazacyclononane-triacetic acid (NOTA)-chelator to bind [⁶⁸Ga]Ga or [¹⁸F]AlF. The radioligands were evaluated by in vivo PET imaging and ex vivo γ-counting of turpentine-induced sterile skin/muscle inflammation in Sprague-Dawley rats. Both tracers showed clear accumulation in the inflamed tissues. The whole-body biodistribution patterns of the tracers were similar. Full article

(This article belongs to the Special Issue Medicinal Chemistry in Europe)

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27 pages, 2488 KiB

Open AccessArticle

Synthesis and Biological Evaluations of NO-Donating Oxa- and Aza-Pentacycloundecane Derivatives as Potential Neuroprotective Candidates

by Rajan Sharma

, Jacques Joubert and Sarel F. Malan^*

Pharmaceutical Chemistry, School of Pharmacy, University of the Western Cape, Private Bag X17, Bellville 7535, South Africa

Molecules 2018, 23(2), 308; https://doi.org/10.3390/molecules23020308 - 31 Jan 2018

Cited by 10 | Viewed by 3237

Abstract

In order to utilize the neuroprotective properties of polycyclic cage compounds, and explore the NO-donating ability of nitrophenyl groups, an array of compounds was synthesized where the different nitrophenyl groups were appended on oxa and aza-bridged cage derivatives. Biological evaluations of the compounds [...] Read more.

In order to utilize the neuroprotective properties of polycyclic cage compounds, and explore the NO-donating ability of nitrophenyl groups, an array of compounds was synthesized where the different nitrophenyl groups were appended on oxa and aza-bridged cage derivatives. Biological evaluations of the compounds were done for cytotoxicity, neuroprotective abilities, the inhibition of N-methyl-d-aspartate (NMDA)-mediated Ca²⁺ influx, the inhibition of voltage-mediated Ca²⁺ influx, and S-nitrosylation abilities. All of the compounds showed low toxicity. With a few exceptions, most of the compounds displayed good neuroprotection and showed inhibitory activity for NMDA-mediated and voltage-gated calcium influx, ranging from high (>70%) to low (20–39%) inhibition. In the S-nitrosylation assay, the compounds with the nitro moiety as the NO-donating group exhibited low to good nitrosylation potency compared to the positive controls. From the biological evaluation of the tested compounds, it was not possible to obtain a simple correlation that could explain the results across all of the biological study domains. This can be ascribed to the independent processes evaluated in the different assays, which reiterate that neuroprotection is a result of multifactorial biochemical mechanisms and interactions. However, these results signify the important aspects of the pentacylcoundecylamine neuroprotectants across different biological study realms. Full article

(This article belongs to the Special Issue Neuroprotective Agents)

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7 pages, 1010 KiB

Open AccessArticle

Synthesis of Scutellarein Derivatives with a Long Aliphatic Chain and Their Biological Evaluation against Human Cancer Cells

by Guanghui Ni^1,2, Yanling Tang¹, Minxin Li¹, Yuefeng He^3,* and Gaoxiong Rao^1,2,*

¹ College of Pharmaceutic Science, Yunnan University of Traditional Chinese Medicine, Kunming 650500, China

² Engineering Laboratory for National Healthcare Theories and Products of Yunnan Province, Yunnan University of Traditional Chinese Medicine, Kunming 650500, China

³ School of Public Health, Kunming Medical University, Kunming 650500, China

Molecules 2018, 23(2), 310; https://doi.org/10.3390/molecules23020310 - 1 Feb 2018

Cited by 15 | Viewed by 3742

Abstract

Scutellarin is the major active flavonoid extracted from the traditional Chinese herbal medicine Erigeron breviscapus (Vant.) Hand-Mazz., which is widely used in China. Recently, accumulating evidence has highlighted the potential role of scutellarin and its main metabolite scutellarein in the treatment of cancer. [...] Read more.

Scutellarin is the major active flavonoid extracted from the traditional Chinese herbal medicine Erigeron breviscapus (Vant.) Hand-Mazz., which is widely used in China. Recently, accumulating evidence has highlighted the potential role of scutellarin and its main metabolite scutellarein in the treatment of cancer. To explore novel anticancer agents with high efficiency, a series of new scutellarein derivatives with a long aliphatic chain were synthesized, and the antiproliferative activities against Jurkat, HCT-116 and MDA-MB-231 cancer cell lines were assessed. Among them, compound 6a exhibited the strongest antiproliferative effects on Jurkat (IC₅₀ = 1.80 μM), HCT-116 (IC₅₀ = 11.50 μM) and MDA-MB-231 (IC₅₀ = 53.91 μM). In particular, 6a even showed stronger antiproliferative effects than the positive control NaAsO₂ on Jurkat and HCT-116 cell lines. The results showed that a proper long aliphatic chain enhanced the antiproliferative activity of scutellarein. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 700 KiB

Open AccessArticle

Antioxidant Activity of Zein Hydrolysates from Zea Species and Their Cytotoxic Effects in a Hepatic Cell Culture

by Jorge L. Díaz-Gómez¹, Margarita Ortíz-Martínez¹

, Oscar Aguilar²

, Silverio García-Lara¹

and Fabiola Castorena-Torres^3,*

¹ Agri-Foods Unit. Tecnologico de Monterrey, Campus Monterrey, 64890 Nuevo León, Mexico

² Escuela de Ingenieria y Ciencias. Tecnologico de Monterrey, 64890 Nuevo León, Mexico

³ Escuela de Medicina, Tecnologico de Monterrey, 64710 Nuevo León, Mexico

Molecules 2018, 23(2), 312; https://doi.org/10.3390/molecules23020312 - 2 Feb 2018

Cited by 26 | Viewed by 5416

Abstract

In recent years, food proteins with bioactivity have been studied for cancer treatment. Zein peptides have shown an important set of bioactivities. This work compares the cytotoxic activity of zein hydrolyzed, extracted from four Zea species: teosinte, native, hybrid, and transgenic (Teo, Nat, [...] Read more.

In recent years, food proteins with bioactivity have been studied for cancer treatment. Zein peptides have shown an important set of bioactivities. This work compares the cytotoxic activity of zein hydrolyzed, extracted from four Zea species: teosinte, native, hybrid, and transgenic (Teo, Nat, Hyb, and HT) in a hepatic cell culture. Zein fraction was extracted, quantified, and hydrolyzed. Antioxidant capacity and cytotoxicity assays were performed on HepG2 cells. The levels of expression of caspase 3, 8, and 9 were evaluated in zein-treated cell cultures. Zea parviglumis showed the highest zein content (46.0 mg/g) and antioxidant activity (673.40 TE/g) out of all native zeins. Peptides from Hyb and HT showed high antioxidant activity compared to their native counterparts (1055.45 and 724.32 TE/g, respectively). Cytotoxic activity was observed in the cell culture using peptides of the four Zea species; Teo and Nat (IC50: 1781.63 and 1546.23 ng/mL) had no significant difference between them but showed more cytotoxic activity than Hyb and HT (IC50: 1252.25 and 1155.56 ng/mL). Increased expression of caspase 3 was observed in the peptide-treated HepG2 cells (at least two-fold more with respect to the control sample). These data indicate the potential for zein peptides to prevent or treat cancer, possibly by apoptosis induction. Full article

(This article belongs to the Special Issue Peptide Therapeutics)

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12 pages, 1544 KiB

Open AccessArticle

Tulbaghia violacea and Allium ursinum Extracts Exhibit Anti-Parasitic and Antimicrobial Activities

by Sonja Krstin^*, Mansour Sobeh

, Markus Santhosh Braun

and Michael Wink^*

Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany

Molecules 2018, 23(2), 313; https://doi.org/10.3390/molecules23020313 - 2 Feb 2018

Cited by 21 | Viewed by 4727

Abstract

Garlic has played an important role in culinary arts and remedies in the traditional medicine throughout human history. Parasitic infections represent a burden in the society of especially poor countries, causing more than 1 billion infections every year and leading to around one [...] Read more.

Garlic has played an important role in culinary arts and remedies in the traditional medicine throughout human history. Parasitic infections represent a burden in the society of especially poor countries, causing more than 1 billion infections every year and leading to around one million deaths. In this study, we investigated the mode of anti-parasitic activity of “wild garlics” Tulbaghia violacea and Allium ursinum dichloromethane extracts against parasites Trypanosoma brucei brucei and Leishmania tarentolae with regard to their already known antimicrobial activity. We also evaluated their cytotoxic potential against human cells. Both extracts showed a relevant trypanocidal and leishmanicidal activity, although L. tarentolae was less sensitive. We determined that the probable mode of action of both extracts is the irreversible inhibition of the activity of Trypanosoma brucei trypanothione reductase enzyme. The extracts showed a mild cytotoxic activity against human keratinocytes. They also exhibited weak—in most cases comparable—antibacterial and antifungal activity. HPLC-MS/MS analysis showed that both extracts are abundant in sulfur compounds. Thus, for the first time, the ability of Allium ursinum and Tulbaghia violacea to kill Trypanosoma sp. and Leishmania sp. parasites, probably by binding to and inactivating sulfur-containing compounds essential for the survival of the parasite, is shown. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 1755 KiB

Open AccessArticle

Lipase-Catalyzed Acidolysis of Egg-Yolk Phosphatidylcholine with Citronellic Acid. New Insight into Synthesis of Isoprenoid-Phospholipids

by Magdalena Rychlicka, Natalia Niezgoda and Anna Gliszczyńska^*

Department of Chemistry, Wroclaw University of Environmental and Life Sciences, Norwida 25, 50–375 Wrocław, Poland

Molecules 2018, 23(2), 314; https://doi.org/10.3390/molecules23020314 - 2 Feb 2018

Cited by 15 | Viewed by 5303

Abstract

The development of a biotechnological method for the production of new biologically active phosphatidylcholine containing monoterpene citronellic acid (CA) was the aim of this work. Incorporation of citronellic acid (CA) into egg-yolk phosphatidylcholine (PC) in the lipase-catalyzed acidolysis process was studied. Isoprenoid acid [...] Read more.

The development of a biotechnological method for the production of new biologically active phosphatidylcholine containing monoterpene citronellic acid (CA) was the aim of this work. Incorporation of citronellic acid (CA) into egg-yolk phosphatidylcholine (PC) in the lipase-catalyzed acidolysis process was studied. Isoprenoid acid CA was used as an acyl donor and five commercially available immobilized lipases were examined as biocatalysts. The effects of organic solvent, enzyme load, reaction time and molar ratio of substrates on the incorporation of citronellic acid (CA) into the phospholipids were evaluated. Modified phospholipid fraction enriched with CA in the sn-1 position (39% of incorporation) was obtained in high 33% yield using Novozym 435 as biocatalyst. In this study a biotechnological method for production of new phospholipid biopreparation enriched with citronellic acid, which can play an important role as a nutraceutical, was applied. Full article

(This article belongs to the Special Issue Frontier in Biocatalysis for Organic Synthesis)

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10 pages, 770 KiB

Open AccessArticle

Nine New Gingerols from the Rhizoma of Zingiber officinale and Their Cytotoxic Activities

by Zezhi Li¹, Yanzhi Wang^1,2,*

, MeiLing Gao¹, Wanhua Cui¹, Mengnan Zeng¹, Yongxian Cheng^1,3 and Juan Li¹

¹ School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China

² Collaborative Innovation Center for Respiratory Disease Diagnosis, Treatment and New Drug Research and Development of Henan Province, Henan University of Chinese Medicine, Zhengzhou 450046, China

³ Guangdong Key Laboratory for Genome Stability & Disease Prevention, School of Pharmaceutical Sciences, School of Medicine, Shenzhen University Health Science Center, Shenzhen 518060, China

Molecules 2018, 23(2), 315; https://doi.org/10.3390/molecules23020315 - 2 Feb 2018

Cited by 24 | Viewed by 5013

Abstract

Nine new gingerols, including three 6-oxo-shogaol derivatives [(Z)-6-oxo-[6]-shogaol (1), (Z)-6-oxo-[8]-shogaol (2), (Z)-6-oxo-[10]-shogaol (3)], one 6-oxoparadol derivative [6-oxo-[6]-paradol (4)], one isoshogaol derivative [(E)-[4]-isoshogaol (5)], and four [...] Read more.

Nine new gingerols, including three 6-oxo-shogaol derivatives [(Z)-6-oxo-[6]-shogaol (1), (Z)-6-oxo-[8]-shogaol (2), (Z)-6-oxo-[10]-shogaol (3)], one 6-oxoparadol derivative [6-oxo-[6]-paradol (4)], one isoshogaol derivative [(E)-[4]-isoshogaol (5)], and four paradoldiene derivatives [(4E,6Z)-[4]-paradoldiene (8), (4E,6E)-[6]-paradoldiene (9), (4E,6E)-[8]-paradoldiene (10), (4E,6Z)-[8]-paradoldiene (11)], together with eight known analogues, were isolated from the rhizoma of Zingiber officinale. Their structures were elucidated on the basis of spectroscopic data. It was noted that the isolation of 6-oxo-shogaol derivatives represents the first report of gingerols containing one 1,4-enedione motif. Their structures were elucidated on the basis of spectroscopic and HRESIMS data. All the new compounds were evaluated for their cytotoxic activities against human cancer cells (MCF-7, HepG-2, KYSE-150). Full article

(This article belongs to the Special Issue Chemical Biology of Sterols, Triterpenoids and Other Natural Products: A Themed Issue in Honor of Professor W. David Nes on the Occasion of His 65th Birthday)

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10 pages, 2257 KiB

Open AccessArticle

MicroRNA-125a-5p Mediates 3T3-L1 Preadipocyte Proliferation and Differentiation

by Yan Xu^1,†, Jingjing Du^1,†, Peiwen Zhang¹, Xue Zhao¹, Qiang Li², Anan Jiang¹, Dongmei Jiang¹, Guoqing Tang¹, Yanzhi Jiang³, Jinyong Wang⁴, Xuewei Li¹, Shunhua Zhang^1,* and Li Zhu^1,*

¹ College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China

² Sichuan Province General Station of Animal Husbandry, Chengdu 611130, China

³ College of Life and Science, Sichuan Agricultural University, Chengdu 611130, China

⁴ Chongqing Academy of Animal Sciences, Chongqing 402460, China

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 317; https://doi.org/10.3390/molecules23020317 - 2 Feb 2018

Cited by 31 | Viewed by 4678

Abstract

Excessive accumulation of adipose tissue is a main cause of obesity or overweight, which is significantly involved in increasing the risk of diseases. Recently, numerous studies have proved that microRNAs (miRNAs) play important roles in adipogenesis by negatively regulating gene expression at posttranscriptional [...] Read more.

Excessive accumulation of adipose tissue is a main cause of obesity or overweight, which is significantly involved in increasing the risk of diseases. Recently, numerous studies have proved that microRNAs (miRNAs) play important roles in adipogenesis by negatively regulating gene expression at posttranscriptional levels. In this study, we showed that miR-125a-5p was expressed at lower levels in the adipose tissues of high-fat diet (HFD)-fed mice than the normal chow (NCW)-fed mice. MiR-125a-5p expression were strongly up-regulated by nearly five-fold, when 3T3-L1 preadipocyte were induced and differentiated into mature adipocytes. Functional analysis indicated that overexpression of miR-125a-5p promoted 3T3-L1 preadipocyte proliferation and inhibited its differentiation. By contrast, inhibition of miR-125a-5p repressed 3T3-L1 preadipocyte proliferation and accelerated its differentiation. Furthermore, a dual-luciferase reporter assay demonstrated that signal transducer and activator of transcription 3 (STAT3) is a direct target gene of miR-125a-5p during 3T3-L1 preadipocyte differentiation. Further analysis confirmed that the process of miR-125a-5p inhibiting 3T3-L1 preadipocyte differentiation might be associated with the regulation of fatty acid metabolism related genes. Taken together, our results indicated that miR-125a-5p might promote 3T3-L1 preadipocyte proliferation, whereas inhibiting 3T3-L1 preadipocyte differentiation by negatively regulating STAT3. Full article

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11 pages, 4074 KiB

Open AccessArticle

Graphene-Derivatized Silica Composite as Solid-Phase Extraction Sorbent Combined with GC–MS/MS for the Determination of Polycyclic Musks in Aqueous Samples

by Cheng Li^1,2, Jiayi Chen^1,2, Yan Chen^1,2, Jihua Wang¹, Hua Ping¹ and Anxiang Lu^1,2,*

¹ Beijing Research Center for Agricultural Standards and Testing, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China

² Beijing Municipal Key Laboratory of Agriculture Environment Monitoring, Beijing 100097, China

Molecules 2018, 23(2), 318; https://doi.org/10.3390/molecules23020318 - 2 Feb 2018

Cited by 15 | Viewed by 4637

Abstract

Polycyclic musks (PCMs) have recently received growing attention as emerging contaminants because of their bioaccumulation and potential ecotoxicological effects. Herein, an effective method for the determination of five PCMs in aqueous samples is presented. Reduced graphene oxide-derivatized silica (rGO@silica) particles were prepared from [...] Read more.

Polycyclic musks (PCMs) have recently received growing attention as emerging contaminants because of their bioaccumulation and potential ecotoxicological effects. Herein, an effective method for the determination of five PCMs in aqueous samples is presented. Reduced graphene oxide-derivatized silica (rGO@silica) particles were prepared from graphene oxide and aminosilica microparticles and characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. PCMs were preconcentrated using rGO@silica as the solid-phase extraction sorbent and quantified by gas chromatography–tandem mass spectrometry. Several experimental parameters, such as eluent, elution volume, sorbent amount, pH, and sample volume were optimized. The correlation coefficient (R) ranged from 0.9958 to 0.9992, while the limits of detection and quantitation for the five PCMs were 0.3–0.8 ng/L and 1.1–2.1 ng/L, respectively. Satisfactory recoveries were obtained for tap water (86.6–105.9%) and river water samples (82.9–107.1%), with relative standard deviations <10% under optimal conditions. The developed method was applied to analyze PCMs in tap and river water samples from Beijing, China. Galaxolide (HHCB) and tonalide (AHTN) were the main PCM components detected in one river water sample at concentrations of 18.7 for HHCB, and 11.7 ng/L for AHTN. Full article

(This article belongs to the Special Issue Solid Phase Extraction: State of the Art and Future Perspectives)

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14 pages, 2029 KiB

Open AccessArticle

Nutritional Value, Chemical Characterization and Bulb Morphology of Greek Garlic Landraces

by Spyridon A. Petropoulos^1,*

, Ângela Fernandes², Georgia Ntatsi³, Konstantinos Petrotos⁴, Lillian Barros^2,5 and Isabel C. F. R. Ferreira^2,*

¹ Department of Agriculture, University of Thessaly, Crop Production and Rural Environment, N. Ionia, 38446 Magnissia, Greece

² Mountain Research Centre (CIMO), ESA, Polytechnic Institute of Bragança, Campus de Santa Apolónia, 1172, 5300-253 Bragança, Portugal

³ Department of Crop Production, Agricultural University of Athens, Iera Odos 75, 11855 Athens, Greece

⁴ Department of Biosystems Engineering, Technological Educational Institute of Thessaly, 41110 Larissa, Greece

⁵ Laboratory of Separation and Reaction Engineering-Laboratory of Catalysis and Materials (LSRE-LCM), Polytechnic Institute of Bragança, Campus de Santa Apolónia, 1172, 5300-253 Braganza, Portugal

Molecules 2018, 23(2), 319; https://doi.org/10.3390/molecules23020319 - 2 Feb 2018

Cited by 49 | Viewed by 7441

Abstract

Garlic (Allium sativum L.) is an important vegetable crop throughout the world. In Greece there are many areas which have specialized in garlic cultivation through the last decades, considered the main production areas. However, despite the significance of garlic as a food [...] Read more.

Garlic (Allium sativum L.) is an important vegetable crop throughout the world. In Greece there are many areas which have specialized in garlic cultivation through the last decades, considered the main production areas. However, despite the significance of garlic as a food product and the high annual income of this crop, there is a decreasing trend in total cultivated area in Greece, and the local landraces are gradually neglected in favor of new imported genotypes. In the present study, garlic genotypes (local landraces/varieties, imported genotypes, commercial cultivars) from the main production regions of Greece were assessed for their chemical composition and quality (total soluble solids, dry matter content, nutritional value, mineral composition, organic acids, fatty acids content and free sugars content), and bulb morphology. The results of the present study showed significant diversity in quality features and bulb morphology, not only between the genotypes from different growing regions, but also between those of the same region. This result is interesting since it could be implemented for further improvement and valorization of this important vegetable crop through extensive breeding programs within the framework of sustainability and genetic, material conservation. Full article

(This article belongs to the Collection Bioactive Compounds)

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12 pages, 2957 KiB

Open AccessArticle

Relationship between the Polymeric Ionization Degree and Powder and Surface Properties in Materials Derived from Poly(maleic anhydride-alt-octadecene)

by Constain H. Salamanca^1,2,*

, Cristhian J. Yarce¹, Camilo A. Zapata² and Jonnathan A. Giraldo²

¹ Programa de Maestría en Formulación de Productos Químicosy Derivados, Facultad de Ciencias Naturales, Universidad Icesi, Calle 18 No. 122–135, Cali 760031, Colombia

² Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Naturales, Universidad Icesi, Calle 18 No. 122–135, Cali 760031, Colombia

Molecules 2018, 23(2), 320; https://doi.org/10.3390/molecules23020320 - 2 Feb 2018

Cited by 7 | Viewed by 4422

Abstract

Polymeric materials derived from poly(maleic anhydride-alt-octadecene)—here referred as PAM-18—have shown interesting properties that make them potential pharmaceutical excipients. In this work, eight polymers derived from PAM-18 were obtained using NaOH and KOH at 1:1; 1:0.75, 1:0.5, and 1:0.25 molar ratios. The [...] Read more.

Polymeric materials derived from poly(maleic anhydride-alt-octadecene)—here referred as PAM-18—have shown interesting properties that make them potential pharmaceutical excipients. In this work, eight polymers derived from PAM-18 were obtained using NaOH and KOH at 1:1; 1:0.75, 1:0.5, and 1:0.25 molar ratios. The resulting products were labeled as PAM-18Na and PAM-18K, respectively. Each polymer was purified by ultrafiltration/lyophilization, and the ionization degree was determined by potentiometric studies, which was related to the zeta potential. The structural characterization was performed using the Fourier transform infrared (FT-IR) espectroscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and X-ray diffraction (XRD) techniques. The physical characterization was carried out by SEM, particle analysis, and humidity loss and gain studies; the surface studies were performed by the sessile drop method. PAM-18Na had ionization degrees of 95%, 63%, 39% and 22%, whereas those for PAM-18K were 99%, 52%, 35% and 20%, respectively. The results also showed that for higher inorganic base amounts used, the polymeric materials obtained possess high ionization degrees, which could form polymeric solutions or hetero-dispersed systems. Likewise, it was observed that for higher proportions of carboxylate groups in the polymeric structure, the capability to retain water is increased and, only can be eliminated by drying at temperatures greater than 160 °C. On the other hand, the modification of PAM-18 to its ionized forms led to the formation of powder materials with low flowability and surfaces that ranged from very hydrophobic to slightly wettable. Full article

(This article belongs to the Special Issue Functional Molecular Materials)

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14 pages, 2886 KiB

Open AccessFeature PaperArticle

Carbamates as Potential Prodrugs and a New Warhead for HDAC Inhibition

by Kristina King¹, Alexander-Thomas Hauser¹, Jelena Melesina²

, Wolfgang Sippl²

and Manfred Jung^1,*

¹ Institute of Pharmaceutical Sciences, Albert-Ludwigs-University Freiburg, Albertstraße 25, 79104 Freiburg im Breisgau, Germany

² Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Wolfgang-Langenbeck-Straße 4, 06120 Halle (Saale), Germany

Molecules 2018, 23(2), 321; https://doi.org/10.3390/molecules23020321 - 2 Feb 2018

Cited by 7 | Viewed by 6709

Abstract

We designed and synthesized carbamates of the clinically-approved HDAC (histone deacetylase) inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA) in order to validate our previously-proposed hypothesis that these carbamates might serve as prodrugs for hydroxamic acid containing HDAC inhibitors. Biochemical assays proved our new compounds [...] Read more.

We designed and synthesized carbamates of the clinically-approved HDAC (histone deacetylase) inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA) in order to validate our previously-proposed hypothesis that these carbamates might serve as prodrugs for hydroxamic acid containing HDAC inhibitors. Biochemical assays proved our new compounds to be potent inhibitors of histone deacetylases in vitro, and they also showed antiproliferative effects in leukemic cells. These results, as well as stability analysis led to the suggestion that the intact carbamates are inhibitors of histone deacetylases themselves, representing a new zinc-binding warhead in HDAC inhibitor design. This suggestion was further supported by the synthesis and evaluation of a carbamate derivative of the HDAC6-selective inhibitor bufexamac. Full article

(This article belongs to the Special Issue Modulators of Histone Acetylation: A Medicinal Chemistry Perspective)

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14 pages, 3747 KiB

Open AccessArticle

Oleanolic Acid-amino Acids Derivatives: Design, Synthesis, and Hepatoprotective Evaluation In Vitro and In Vivo

by Fuhao Chu

, Wenxi Zhang, Wenbo Guo, Zhaoyi Wang, Yuqin Yang, Xinyu Zhang, Kang Fang, Mengmeng Yan, Penglong Wang^*

and Haimin Lei^*

School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China

Molecules 2018, 23(2), 322; https://doi.org/10.3390/molecules23020322 - 2 Feb 2018

Cited by 22 | Viewed by 3926

Abstract

Activated hepatic stellate cells (HSCs) are the main extracellular matrix (ECM)-producing cells in the injured liver and the key mediators of liver fibrosis; they also promote the progression of hepatocellular carcinoma (HCC). In the acidic extracellular microenvironment of HCC, HSCs are activated to [...] Read more.

Activated hepatic stellate cells (HSCs) are the main extracellular matrix (ECM)-producing cells in the injured liver and the key mediators of liver fibrosis; they also promote the progression of hepatocellular carcinoma (HCC). In the acidic extracellular microenvironment of HCC, HSCs are activated to promote the migration of HCC cells. It is worth attempting to alter the weak acidic microenvironment to promote activated HSC apoptosis to treat liver fibrosis and liver cancer. In the present study, a series of novel OA-amino acids analogues were designed and synthesized to introduce different amino acids in the 3-hydroxyl of OA using the ester condensation reaction to enhance hydrophilicity, alkalinity, and biological activity. We found that OA-lysine derivative (3g) could improve the hydrophilic of OA and induce HSCs apoptosis via inducing MMP depolarization and increasing intracellular Ca²⁺ levels. Additionally, 3g displayed a better hepatoprotective effect than OA (20 mg/kg, intragastric administration) against the acute liver injury induced by carbon tetrachloride (CCl₄) in mice. The results suggested that basic amino acids (lysine) could effectively enhance OA’s hydrophilicity, alkalinity, and hepatoprotective activity in vitro and in vivo, which might be likely associated with increasing bioavailability and altering an extracellular weak acidic microenvironment with further verification. Therefore, the OA-lysine derivative (3g) has the potential to be developed as an agent with hepatoprotective activity. Full article

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15 pages, 2656 KiB

Open AccessArticle

The Biological Properties and Potential Interacting Proteins of d-Alanyl-d-alanine Ligase A from Mycobacterium tuberculosis

by Shufeng Yang, Yuefei Xu, Yan Wang, Feng Ren, Sheng Li, Wenyong Ding, Yufang Ma^* and Wenli Zhang^*

Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian 116044, China

Molecules 2018, 23(2), 324; https://doi.org/10.3390/molecules23020324 - 3 Feb 2018

Cited by 15 | Viewed by 5315

Abstract

(1) Background: d-alanine-d-alanine ligase (DdlA), an effective target for drug development to combat against Mycobacterium tuberculosis (Mtb), which threatens human health globally, supplies a substrate of d-alanyl-d-alanine for peptidoglycan crosslinking by catalyzing the dimerization of [...] Read more.

(1) Background: d-alanine-d-alanine ligase (DdlA), an effective target for drug development to combat against Mycobacterium tuberculosis (Mtb), which threatens human health globally, supplies a substrate of d-alanyl-d-alanine for peptidoglycan crosslinking by catalyzing the dimerization of two d-alanines. To obtain a better understanding of DdlA profiles and develop a colorimetric assay for high-throughput inhibitor screening, we focused on explicating and characterizing Tb-DdlA. (2) Methods and Results: Rv2981c (ddlA) was expressed in Escherichia coli, and the purified Tb-DdlA was identified using (anti)-polyhistidine antibody followed by DdlA activity confirmation by measuring the released orthophosphate via colorimetric assay and the yielded d-alanyl-d-alanine through high performance thin layer chromatography (HP-TLC). The kinetic assays on Tb-DdlA indicated that Tb-DdlA exhibited a higher affinity to ATP (K_mATP: 50.327 ± 4.652 μmol/L) than alanine (K_mAla: 1.011 ± 0.094 mmol/L). A colorimetric assay for Tb-DdlA activity was developed for high-throughput screening of DdlA inhibitors in this study. In addition, we presented an analysis on Tb-DdlA interaction partners by pull-down assay and MS/MS. Eight putative interaction partners of Tb-DdlA were identified. (3) Conclusions: Our dataset provided a valuable resource for exploring Tb-DdlA biology, and developed an easy colorimetric assay for screening of Tb-DdlA inhibitors. Full article

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7 pages, 1181 KiB

Open AccessArticle

A Novel Flavonoid Glucoside from the Fruits of Lycium ruthenicun

by Jing-Jing Qi^1,2

, Yong-Ming Yan³, Li-Zhi Cheng³, Bao-Hua Liu^3,*, Fu-Ying Qin^2,3

and Yong-Xian Cheng^1,2,3,4,*

¹ School of Pharmacy, Yunnan University of Traditional Chinese Medicine, Kunming 650500, China

² State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China

³ Guangdong Key Laboratory for Genome Stability & Disease Prevention, School of Pharmaceutical Sciences, School of Medicine, Shenzhen University Health Science Center, Shenzhen 518060, China

⁴ School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450008, China

Molecules 2018, 23(2), 325; https://doi.org/10.3390/molecules23020325 - 3 Feb 2018

Cited by 14 | Viewed by 4059

Abstract

A novel flavonoid glucoside, ruthenicunoid A (1), together with eight known substances, were isolated from the fruits of Lycium ruthenicun Murr. Their structures were elucidated by extensive spectroscopic data and chemical methods. Especially, the absolute configuration of glucose residue in 1 [...] Read more.

A novel flavonoid glucoside, ruthenicunoid A (1), together with eight known substances, were isolated from the fruits of Lycium ruthenicun Murr. Their structures were elucidated by extensive spectroscopic data and chemical methods. Especially, the absolute configuration of glucose residue in 1 was assigned by acid hydrolysis followed by derivatization and GC analysis. Biological evaluation towards Sirtuin 1 (SIRT1) found that compounds 1 and 2 exhibit inhibitory activity against SIRT1 in a concentration-dependent manner, indicating its potential on SIRT1-associated disorders. Full article

(This article belongs to the Special Issue Innovative Extraction Techniques and Hyphenated Instrument Configuration for Complex Matrices Analysis)

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20 pages, 1553 KiB

Open AccessArticle

Non-Imidazole Histamine H₃ Ligands. Part VII. Synthesis, In Vitro and In Vivo Characterization of 5-Substituted-2-thiazol-4-n-propylpiperazines

by Roman Guryn¹, Marek Staszewski¹, Anna Stasiak², Daniel McNaught Flores³, Wiesława Agnieszka Fogel², Rob Leurs³ and Krzysztof Walczyński^1,*

¹ Department of Synthesis and Technology of Drugs, Medical University of Lodz, ul. Muszyńskiego 1, 90-145 Łódź, Poland

² Department of Hormone Biochemistry, Medical University of Lodz, ul. Żeligowskiego 7/9, 90-752 Łódź, Poland

³ Amsterdam Institute of Molecules, Medicines & Systems, Division of Medicinal Chemistry, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands

Molecules 2018, 23(2), 326; https://doi.org/10.3390/molecules23020326 - 3 Feb 2018

Cited by 4 | Viewed by 4638

Abstract

H₃ receptors present on histaminergic and non-histaminergic neurons, act as autoreceptors or heteroreceptors controlling neurotransmitter release and synthesis. Previous, studies have found that the compound N-methyl-N-3-phenylalkyl-2-[2-(4-n-propylpiperazin-1-yl)-1,3-thiazol-5-yl]ethan-1-amine (ADS-531, 2c) exhibits high in vitro potency toward H₃ guinea [...] Read more.

H₃ receptors present on histaminergic and non-histaminergic neurons, act as autoreceptors or heteroreceptors controlling neurotransmitter release and synthesis. Previous, studies have found that the compound N-methyl-N-3-phenylalkyl-2-[2-(4-n-propylpiperazin-1-yl)-1,3-thiazol-5-yl]ethan-1-amine (ADS-531, 2c) exhibits high in vitro potency toward H₃ guinea pig jejunal receptors, with pA₂ = 8.27. To optimize the structure of the lead compound ADS-531, a series of 5-substituted-2-thiazol-4-n-propylpiperazines 3 were synthesized and subjected to in vitro pharmacological characterization; the alkyl chain between position 2 of the thiazole ring and the terminal secondary N-methylamino function was elongated from three to four methylene groups and the N-methylamino functionality was substituted by benzyl-, 2-phenylethyl-, and 3-phenyl-propyl- moieties. SAR studies on novel non-imidazole, 5-substituted-2-thiazol-4-n-propyl-piperazines 3 showed that the most active compound 3a (pA₂ = 8.38), additionally possessed a weak competitive H₁-antagonistic activity. Therefore, compound ADS-531, which did not exhibit any H₁-antagonistic activity, was chosen for further evaluation for its affinity to the recombinant rat and human histamine H₃ receptors (rH₃R and hH₃R, respectively). ADS-531 exhibited nanomolar affinity for both rH₃R and hH₃R receptors. It was also shown that, ADS-531 given subchronically to rats (s.c. 3 mg/kg, 5 days) penetrated the brain, where it affected dopamine, noradrenaline and serotonin concentration; however, it did not affect histamine concentration nor feeding behavior. Full article

(This article belongs to the Special Issue Focusing on Sulfur in Medicinal Chemistry)

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14 pages, 1956 KiB

Open AccessFeature PaperArticle

Synthesis of Two Tetrasaccharide Pentenyl Glycosides Related to the Pectic Rhamnogalacturonan I Polysaccharide

by Alexandra N. Zakharova^1,2, Shahid I. Awan^1,2

, Faranak Nami^1,2, Charlotte H. Gotfredsen², Robert Madsen² and Mads H. Clausen^1,2,*

¹ Center for Nanomedicine and Theranostics, Technical University of Denmark, Kemitorvet 207, DK-2800 Kgs. Lyngby, Denmark

² Department of Chemistry, Technical University of Denmark, Kemitorvet 207, DK-2800 Kgs. Lyngby, Denmark

Molecules 2018, 23(2), 327; https://doi.org/10.3390/molecules23020327 - 3 Feb 2018

Cited by 2 | Viewed by 4113

Abstract

The synthesis of two protected tetrasaccharide pentenyl glycosides with diarabinan and digalactan branching related to the pectic polysaccharide rhamnogalacturonan I is reported. The strategy relies on the coupling of N-phenyl trifluoroacetimidate disaccharide donors to a common rhamnosyl acceptor. The resulting trisaccharide thioglycosides [...] Read more.

The synthesis of two protected tetrasaccharide pentenyl glycosides with diarabinan and digalactan branching related to the pectic polysaccharide rhamnogalacturonan I is reported. The strategy relies on the coupling of N-phenyl trifluoroacetimidate disaccharide donors to a common rhamnosyl acceptor. The resulting trisaccharide thioglycosides were finally coupled to an n-pentenyl galactoside acceptor to access the two protected branched tetrasaccharides. Full article

(This article belongs to the Special Issue Oligosaccharide Synthesis)

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29 pages, 5011 KiB

Open AccessArticle

Prediction of Disordered Regions and Their Roles in the Anti-Pathogenic and Immunomodulatory Functions of Butyrophilins

by Elrashdy M. Redwan^1,2,*

, Ahmed M. Al-Hejin¹, Hussein A. Almehdar¹, Abdelrahman M. Elsaway³ and Vladimir N. Uversky^1,4,5,*

¹ Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah, PO Box 80203, Jeddah 21589, Saudi Arabia

² Therapeutic and Protective Proteins Laboratory, Protein Research Department, Genetic Engineering and Biotechnology Research Institute GEBRI, City for Scientific Research and Technology Applications, New Borg EL Arab 21934, Alexandria, Egypt

³ Microbiology Department, Faculty of Medicine, Al-Azhar University, Cairo 11651, Egypt

⁴ Department of Molecular Medicine and USF Health Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA

⁵ Laboratory of New Methods in Biology, Institute for Biological Instrumentation, Russian Academy of Sciences, Pushchino 142290, Moscow Region, Russia

Molecules 2018, 23(2), 328; https://doi.org/10.3390/molecules23020328 - 4 Feb 2018

Cited by 10 | Viewed by 6015

Abstract

Butyrophilins (BTNs) are a group of the moonlighting proteins, some members of which are secreted in milk. They constitute a large family of structurally similar type 1 transmembrane proteins from the immunoglobulin superfamily. Although the founding member of this family is related to [...] Read more.

Butyrophilins (BTNs) are a group of the moonlighting proteins, some members of which are secreted in milk. They constitute a large family of structurally similar type 1 transmembrane proteins from the immunoglobulin superfamily. Although the founding member of this family is related to lactation, participating in the secretion, formation and stabilization of milk fat globules, it may also have a cell surface receptor function. Generally, the BTN family members are known to modulate co-stimulatory responses, T cell selection, differentiation, and cell fate determination. Polymorphism of these genes was shown to be associated with the pathology of several human diseases. Despite their biological significance, structural information on human butyrophilins is rather limited. Based on their remarkable multifunctionality, butyrophilins seem to belong to the category of moonlighting proteins, which are known to contain intrinsically disordered protein regions (IDPRs). However, the disorder status of human BTNs was not systematically investigated as of yet. The goal of this study is to fill this gap and to evaluate peculiarities of intrinsic disorder predisposition of the members of human BTN family, and to find if they have IDPRs that can be attributed to the multifunctionality of these important proteins. Full article

(This article belongs to the Section Bioorganic Chemistry)

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17 pages, 3496 KiB

Open AccessArticle

Role of Cationic Side Chains in the Antimicrobial Activity of C18G

by Eric M. Kohn^1,2,†, David J. Shirley^1,†, Lubov Arotsky¹, Angela M. Picciano¹, Zachary Ridgway¹, Michael W. Urban¹, Benjamin R. Carone³ and Gregory A. Caputo^1,3,*

¹ Department of Chemistry and Biochemistry, Rowan University, Glassboro, NJ 08028, USA

² Thomas N. Bantivoglio Honors Concentration, Rowan University, Glassboro, NJ 08028, USA

³ Department of Molecular and Cellular Biosciences, Rowan University, Glassboro, NJ 08028, USA

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 329; https://doi.org/10.3390/molecules23020329 - 4 Feb 2018

Cited by 39 | Viewed by 8507

Abstract

Antimicrobial peptides (AMPs) have been an area of great interest, due to the high selectivity of these molecules toward bacterial targets over host cells and the limited development of bacterial resistance to these molecules throughout evolution. The peptide C18G has been shown to [...] Read more.

Antimicrobial peptides (AMPs) have been an area of great interest, due to the high selectivity of these molecules toward bacterial targets over host cells and the limited development of bacterial resistance to these molecules throughout evolution. The peptide C18G has been shown to be a selective, broad spectrum AMP with a net +8 cationic charge from seven lysine residues in the sequence. In this work, the cationic Lys residues were replaced with other natural or non-proteinogenic cationic amino acids: arginine, histidine, ornithine, or diaminopropionic acid. These changes vary in the structure of the amino acid side chain, the identity of the cationic moiety, and the pK_a of the cationic group. Using a combination of spectroscopic and microbiological methods, the influence of these cationic groups on membrane binding, secondary structure, and antibacterial activity was investigated. The replacement of Lys with most other cationic residues had, at most, 2-fold effects on minimal inhibitory concentration against a variety of Gram-positive and Gram-negative bacteria. However, the peptide containing His as the cationic group showed dramatically reduced activity. All peptide variants retained the ability to bind lipid vesicles and showed clear preference for binding vesicles that contained anionic lipids. Similarly, all peptides adopted a helical conformation when bound to lipids or membrane mimetics, although the peptide containing diaminopropionic acid exhibited a decreased helicity. The peptides exhibited a wider variety of activity in the permeabilization of bacterial membranes, with peptides containing Lys, Arg, or Orn being the most broadly active. In all, the antibacterial activity of the C18G peptide is generally tolerant to changes in the structure and identity of the cationic amino acids, yielding new possibilities for design and development of AMPs that may be less susceptible to immune and bacterial recognition or in vivo degradation. Full article

(This article belongs to the Special Issue Antimicrobial Peptides and Peptidomimetics)

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16 pages, 17246 KiB

Open AccessArticle

Non-Covalent Supported of l-Proline on Graphene Oxide/Fe₃O₄ Nanocomposite: A Novel, Highly Efficient and Superparamagnetically Separable Catalyst for the Synthesis of Bis-Pyrazole Derivatives

by Mosadegh Keshavarz¹, Amanollah Zarei Ahmady^2,3,*

, Luigi Vaccaro⁴

and Maryam Kardani⁵

¹ Department of Gas and Petroleum, Yasouj University, Gachsaran 75918-74831, Iran

² Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 14536-33143, Iran

³ Department of Medicinal Chemistry, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 14536-33143, Iran

⁴ Department of Chemistry, Biology and Biotechnology, University of Perugia, 06123 Perugia, Italy

⁵ Marine Pharmaceutical Science Research Center, Ahvaz JundiShapur University of Medical sciences, Ahvaz 14536-33143, Iran

Molecules 2018, 23(2), 330; https://doi.org/10.3390/molecules23020330 - 5 Feb 2018

Cited by 35 | Viewed by 6200

Abstract

A superparamagnetic graphene oxide/Fe₃O₄/l-proline nano hybrid that was obtained from the non-covalent immobilization of l-proline on graphene oxide/Fe₃O₄ nanocomposite was used as a new magnetically separable catalyst for the efficient synthesis of 4,4′-(arylmethylene) [...] Read more.

A superparamagnetic graphene oxide/Fe₃O₄/l-proline nano hybrid that was obtained from the non-covalent immobilization of l-proline on graphene oxide/Fe₃O₄ nanocomposite was used as a new magnetically separable catalyst for the efficient synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ol) derivatives. The prepared heterogeneous catalyst was characterized using FTIR, TGA, DTG, XRD, TEM, SEM, and elemental analysis techniques. Short reaction times (5–15 min), excellent yields (87–98%), and simple experimental procedure with an easy work-up are some of the advantages of the introduced catalyst. Full article

(This article belongs to the Section Nanochemistry)

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10 pages, 1438 KiB

Open AccessArticle

Anti-Inflammatory Effect of Melittin on Porphyromonas Gingivalis LPS-Stimulated Human Keratinocytes

by Woon-Hae Kim¹

, Hyun-Jin An¹, Jung-Yeon Kim¹, Mi-Gyeong Gwon¹, Hyemin Gu¹, Minji Jeon¹, Min-Kyung Kim²

, Sang-Mi Han³ and Kwan-Kyu Park^1,*

¹ Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu 42472, Korea

² Department of Pathology, College of Medicine, Dongguk University, Gyeongju-si 38066, Korea

³ Department of Agricultural Biology, National Academy of Agricultural Science, RDA, 300, Nongsaengmyeong-ro, Wansan-gu, Jeonju-si, Jeollabuk-do 55365, Korea

Molecules 2018, 23(2), 332; https://doi.org/10.3390/molecules23020332 - 5 Feb 2018

Cited by 36 | Viewed by 7862

Abstract

Periodontitis is a chronic inflammatory disease that contributes to the destruction of the gingiva. Porphyromonas gingivalis (P. gingivalis) can cause periodontitis via its pathogenic lipopolysaccharides (LPS). Melittin, a major component of bee venom, is known to have anti-inflammatory and antibacterial effects. [...] Read more.

Periodontitis is a chronic inflammatory disease that contributes to the destruction of the gingiva. Porphyromonas gingivalis (P. gingivalis) can cause periodontitis via its pathogenic lipopolysaccharides (LPS). Melittin, a major component of bee venom, is known to have anti-inflammatory and antibacterial effects. However, the role of melittin in the inflammatory response has not been elucidated in periodontitis-like human keratinocytes. Therefore, we investigated the anti-inflammatory effects of melittin on a P. gingivalis LPS (PgLPS)-treated HaCaT human keratinocyte cell line. The cytotoxicity of melittin was measured using a human keratinocyte cell line, HaCaT, and a Cell Counting Kit-8. The effect of melittin on PgLPS-induced inflammation was determined with Western blot, real-time quantitative PCT, and immunofluorescence. PgLPS increased the expression of toll-like receptor (TLR) 4 and proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and interferon-γ (IFN-γ). Moreover, PgLPS induced activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), extracellular signal-regulated kinase (ERK), and protein kinase B/Akt. Melittin also inhibited the expression of proinflammatory cytokines by suppressing the activation of the NF-κB signaling pathway, ERK, and Akt. Melittin attenuates the PgLPS-induced inflammatory response and could therefore be applied in the treatment of periodontitis for anti-inflammatory effects. Full article

(This article belongs to the Special Issue Natural Toxins/Molecules (and Derivatives) from Animal Venoms: From Basic Research to Therapeutic Applications)

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14 pages, 2603 KiB

Open AccessArticle

The Fungal Metabolite Eurochevalierine, a Sequiterpene Alkaloid, Displays Anti-Cancer Properties through Selective Sirtuin 1/2 Inhibition

by Michael Schnekenburger¹

, Véronique Mathieu², Florence Lefranc³, Jun Young Jang⁴, Marco Masi⁵

, Anake Kijjoa⁶

, Antonio Evidente⁵, Hyun-Jung Kim⁷, Robert Kiss⁸, Mario Dicato¹, Byung Woo Han^4,*

and Marc Diederich^4,*

¹ Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg

² Department of Pharmacotherapy and Pharmaceutics, Faculté de Pharmacie, Université Libre de Bruxelles, Boulevard du Triomphe, 1050 Brussels, Belgium

³ Service de Neurochirurgie, Hôpital Erasme, Université Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium

⁴ Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, 1 Gwanak-ro Gwanak-gu, Seoul 08826, Korea

⁵ Dipartimento di Scienze Chimiche, Università di Napoli Federico II, Via Cintia 4, 80126 Napoli, Italy

⁶ Instituto de Ciências Biomédicas de Abel Salazar (ICBAS) and CIIMAR, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal

⁷ College of Pharmacy, Chung-Ang University, 84 Heukseok-ro Dongjak-gu, Seoul 06974, Korea

⁸ Retired – previously Director of Research at the Fonds National de la Recherche Scientifique (FRS-FNRS; Belgium)

Molecules 2018, 23(2), 333; https://doi.org/10.3390/molecules23020333 - 5 Feb 2018

Cited by 14 | Viewed by 4572

Abstract

NAD⁺-dependent histone deacetylases (sirtuins) are implicated in cellular processes such as proliferation, DNA repair, and apoptosis by regulating gene expression and the functions of numerous proteins. Due to their key role in cells, the discovery of small molecule sirtuin modulators has [...] Read more.

NAD⁺-dependent histone deacetylases (sirtuins) are implicated in cellular processes such as proliferation, DNA repair, and apoptosis by regulating gene expression and the functions of numerous proteins. Due to their key role in cells, the discovery of small molecule sirtuin modulators has been of significant interest for diverse therapeutic applications. In particular, it has been shown that inhibition of sirtuin 1 and 2 activities is beneficial for cancer treatment. Here, we demonstrate that the fungal metabolite eurochevalierine from the fungus Neosartorya pseudofischeri inhibits sirtuin 1 and 2 activities (IC₅₀ about 10 µM) without affecting sirtuin 3 activity. The binding modes of the eurochevalierine for sirtuin 1 and 2 have been identified through computational docking analyses. Accordingly, this sequiterpene alkaloid induces histone H4 and α-tubulin acetylation in various cancer cell models in which it induces strong cytostatic effects without affecting significantly the viability of healthy PBMCs. Importantly, eurochevalierine targets preferentially cancer cell proliferation (selectivity factor ≫ 7), as normal human primary CD34⁺ stem/progenitor cells were less affected by the treatment. Finally, eurochevalierine displays suitable drug-likeness parameters and therefore represent a promising scaffold for lead molecule optimization to study the mechanism and biological roles of sirtuins and potentially a basis for development into therapeutics. Full article

(This article belongs to the Special Issue Modulators of Histone Acetylation: A Medicinal Chemistry Perspective)

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16 pages, 2451 KiB

Open AccessArticle

Mexican Propolis: A Source of Antioxidants and Anti-Inflammatory Compounds, and Isolation of a Novel Chalcone and ε-Caprolactone Derivative

by Silvia Laura Guzmán-Gutiérrez¹, Antonio Nieto-Camacho², Jorge Ivan Castillo-Arellano³, Elizabeth Huerta-Salazar², Griselda Hernández-Pasteur², Mayra Silva-Miranda¹, Omar Argüello-Nájera⁴, Omar Sepúlveda-Robles⁵

, Clara Inés Espitia^6,* and Ricardo Reyes-Chilpa^2,*

¹ Departamento de Inmunología, Catedrática CONACyT-Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán 04510, Ciudad de México, Mexico

² Departamento de Productos Naturales, Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán 04510, Ciudad de México, Mexico

³ Departamento de Farmacobiología, CINVESTAV-SUR, Instituto Politécnico Nacional, Calzada de los Tenorios 235, Col. Granjas Coapa C.P. 14330, Ciudad de México, Mexico

⁴ El Colegio de la Frontera Sur, Ecosur-San Cristóbal, Carretera Panamericana y Periférico Sur s/n Barrio María Auxiliadora, San Cristóbal de Las Casas C.P. 29290, Chiapas, Mexico

⁵ Catedrático CONACyT—Unidad de Investigación Médica en Epidemiología Clínica, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS). Av. Cuauhtémoc No. 330. Colonia Doctores, Delegación Cuauhtémoc C.P. 06720, Ciudad de México, Mexico

⁶ Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán 04510, Ciudad de México, Mexico

Molecules 2018, 23(2), 334; https://doi.org/10.3390/molecules23020334 - 6 Feb 2018

Cited by 45 | Viewed by 6582

Abstract

The propolis produced by bees are used in alternative medicine for treating inflammation, and infections, presumably due to its antioxidant properties. In this context, five propolis from México were investigated to determine their inhibitory lipid peroxidation properties. The ethyl acetate extract from a [...] Read more.

The propolis produced by bees are used in alternative medicine for treating inflammation, and infections, presumably due to its antioxidant properties. In this context, five propolis from México were investigated to determine their inhibitory lipid peroxidation properties. The ethyl acetate extract from a red propolis from Chiapas State (4-EAEP) was the most potent (IC₅₀ = 1.42 ± 0.07 μg/mL) in the TBARS assay, and selected for further studies. This extract afforded two new compounds, epoxypinocembrin chalcone (6), and an ε-caprolactone derivative (10), as well as pinostrobin (1), izalpinin (2), cinnamic acid (3), pinocembrin (4), kaempherol (5), 3,3-dimethylallyl caffeate in mixture with isopent-3-enyl caffeate (7a + 7b), 3,4-dimethoxycinnamic acid (8), rhamnetin (9) and caffeic acid (11). The HPLC profile, anti-mycobacterial, and antioxidant properties of this extract was also determined. Most of the isolated compounds were also tested by inhibition of reactive oxygen species (ROS) in challenged mouse bone marrow-derived mast cells (BMMCs), and DPPH. Their anti-inflammatory activity was evaluated by TPA, and MPO (myeloperoxidase) activity by ear edema test in mice. The most potent compounds were 7a + 7b in the TBARS assay (IC₅₀ = 0.49 ± 0.06 μM), and 2 which restored the ROS baseline (3.5 μM). Our results indicate that 4-EAEP has anti-oxidant, and anti-inflammatory properties due to its active compounds, suggesting it has anti-allergy and anti-asthma potential. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 1662 KiB

Open AccessArticle

A Highly Sensitive Immunochromatographic Strip Test for Rapid and Quantitative Detection of Saikosaponin d

by Yue Zhang¹, Wei Xiao², Hui Kong³, Jinjun Cheng³, Xin Yan³, Meiling Zhang³, Qingguo Wang³, Huihua Qu^4,* and Yan Zhao^3,*

¹ School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China

² Jiangsu Kanion Pharmaceutical Co., Ltd., 58 Jiangning Industrial Park Kangyuan Road, Lianyungang, Jiangsu, 210000, China

³ School of Basic Medical Sciences, Beijing University of Chinese Medicine, 11 Beisanhuandong Road, Chaoyang District, Beijing 100029, China

⁴ Centre of Scientific Experiment, Beijing University of Chinese Medicine, 11 Beisanhuandong Road, Chaoyang District, Beijing 100029, China

Molecules 2018, 23(2), 338; https://doi.org/10.3390/molecules23020338 - 6 Feb 2018

Cited by 9 | Viewed by 6157

Abstract

A quantitative lateral-flow immunoassay using gold nanoparticles (AuNPs) conjugated with a monoclonal antibody (MAb) against saikosaponin d (SSd) was developed for the analysis of SSd. The AuNPs were prepared in our laboratory. The AuNPs were polyhedral, with an average diameter of approximately 18 [...] Read more.

A quantitative lateral-flow immunoassay using gold nanoparticles (AuNPs) conjugated with a monoclonal antibody (MAb) against saikosaponin d (SSd) was developed for the analysis of SSd. The AuNPs were prepared in our laboratory. The AuNPs were polyhedral, with an average diameter of approximately 18 nm. We used the conjugation between AuNPs and MAbs against SSd to prepare immunochromatographic strips (ICSs). For the quantitative experiment, the strips with the test results were scanned using a membrane strip reader, and a detection curve (regression equation, y = −0.113ln(x) + 1.5451, R² = 0.983), representing the averages of the scanned data, was obtained. This curve was linear from 96 ng/mL to 150 μg/mL, and the IC₅₀ value was 10.39 μg/mL. In this study, we bring the concept of POCT (point-of-care testing) to the measurement of TCM compounds, and this is the first report of quantitative detection of SSd by an ICS. Full article

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15 pages, 1960 KiB

Open AccessArticle

Chromatographic and Spectroscopic Identification and Recognition of Natural Dyes, Uncommon Dyestuff Components, and Mordants: Case Study of a 16th Century Carpet with Chintamani Motifs

by Olga Otłowska¹, Marek Ślebioda², Agata Kot-Wasik¹, Jakub Karczewski³ and Magdalena Śliwka-Kaszyńska^1,*

¹ Faculty of Chemistry, Gdansk University of Technology, 80-233 Gdansk, Poland

² Perlan Technologies, Sp. z.o.o., 02-785 Warszawa, Poland

³ Faculty of Applied Physics and Mathematics, Gdansk University of Technology, 80-233 Gdansk, Poland

Molecules 2018, 23(2), 339; https://doi.org/10.3390/molecules23020339 - 6 Feb 2018

Cited by 29 | Viewed by 5315

Abstract

A multi-tool analytical practice was used for the characterisation of a 16th century carpet manufactured in Cairo. A mild extraction method with hydrofluoric acid has been evaluated in order to isolate intact flavonoids and their glycosides, anthraquinones, tannins, and indigoids from fibre samples. [...] Read more.

A multi-tool analytical practice was used for the characterisation of a 16th century carpet manufactured in Cairo. A mild extraction method with hydrofluoric acid has been evaluated in order to isolate intact flavonoids and their glycosides, anthraquinones, tannins, and indigoids from fibre samples. High-performance liquid chromatography coupled to spectroscopic and mass spectrometric detectors was used for the identification of possible marker compounds with special attention paid to natural dyes present in the historical samples. Weld, young fustic, and soluble redwood dye were identified as the dye sources in yellow thread samples. Based on the developed method, it was possible to establish that red fibres were coloured with lac dye, whereas green fibre shades were obtained with indigo and weld. Tannin-containing plant material in combination with indigo and weld were used to obtain the brown hue of the thread. Hyphenation of high-performance liquid chromatography (HPLC) with quadrupole time-of-flight mass spectrometry (QTOF MS) and triple-quadrupole mass spectrometry (QqQ MS) enabled us to recognise four uncommon and thus-far unknown dye components that were also found in the historical samples. These compounds probably represent a unique fingerprint of dyed threads manufactured in a Turkish workshop. Scanning electron microscopy with energy-dispersive X-ray detector (SEM-EDS) and Fourier transform infrared spectroscopy (FT-IR) were used for the identification and characterisation of substrates and mordants present in the historical carpet. Carbon and oxygen were detected in large quantities as a part of the wool protein. The presence of aluminium, iron, and calcium indicated their usage as mordants. Trace amounts of copper, silica, and magnesium might originate from the contaminants. FT-IR analysis showed bands characteristic for woollen fibres and SEM micrographs defined the structure of the wool. Full article

(This article belongs to the Section Natural Products Chemistry)

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16 pages, 2666 KiB

Open AccessArticle

Design, Synthesis and in Combo Antidiabetic Bioevaluation of Multitarget Phenylpropanoic Acids

by Blanca Colín-Lozano¹, Samuel Estrada-Soto¹

, Fabiola Chávez-Silva¹, Abraham Gutiérrez-Hernández¹, Litzia Cerón-Romero¹

, Abraham Giacoman-Martínez², Julio Cesar Almanza-Pérez²

, Emanuel Hernández-Núñez³

, Zhilong Wang⁴, Xin Xie⁴, Mario Cappiello⁵

, Francesco Balestri⁵, Umberto Mura⁵ and Gabriel Navarrete-Vazquez^1,*

¹ Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico

² Laboratorio de Farmacología, Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana Iztapalapa, Ciudad de México 09340, Mexico

³ Cátedra CONACyT, Departamento de Recursos del Mar, Centro de Investigación y de Estudios Avanzados del IPN, Unidad Mérida, Yucatán 97310, Mexico

⁴ CAS Key Laboratory of Receptor Research, the National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China, [email protected] (Z.W.)

⁵ Dipartimento di Biologia, Unità di Biochimica, University of Pisa, 56126 Pisa, Italy

Molecules 2018, 23(2), 340; https://doi.org/10.3390/molecules23020340 - 6 Feb 2018

Cited by 38 | Viewed by 6015

Abstract

We have synthesized a small series of five 3-[4-arylmethoxy)phenyl]propanoic acids employing an easy and short synthetic pathway. The compounds were tested in vitro against a set of four protein targets identified as key elements in diabetes: G protein-coupled receptor 40 (GPR40), aldose reductase [...] Read more.

We have synthesized a small series of five 3-[4-arylmethoxy)phenyl]propanoic acids employing an easy and short synthetic pathway. The compounds were tested in vitro against a set of four protein targets identified as key elements in diabetes: G protein-coupled receptor 40 (GPR40), aldose reductase (AKR1B1), peroxisome proliferator-activated receptor gama (PPARγ) and solute carrier family 2 (facilitated glucose transporter), member 4 (GLUT-4). Compound 1 displayed an EC₅₀ value of 0.075 μM against GPR40 and was an AKR1B1 inhibitor, showing IC₅₀ = 7.4 μM. Compounds 2 and 3 act as slightly AKR1B1 inhibitors, potent GPR40 agonists and showed an increase of 2 to 4-times in the mRNA expression of PPARγ, as well as the GLUT-4 levels. Docking studies were conducted in order to explain the polypharmacological mode of action and the interaction binding mode of the most active molecules on these targets, showing several coincidences with co-crystal ligands. Compounds 1–3 were tested in vivo at an explorative 100 mg/kg dose, being 2 and 3 orally actives, reducing glucose levels in a non-insulin-dependent diabetes mice model. Compounds 2 and 3 displayed robust in vitro potency and in vivo efficacy, and could be considered as promising multitarget antidiabetic candidates. This is the first report of a single molecule with these four polypharmacological target action. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 2813 KiB

Open AccessArticle

Modification and Assembly of a Versatile Lactonase for Bacterial Quorum Quenching

by Melissa K. Rhoads^1,2, Pricila Hauk^1,2, Valerie Gupta², Michelle L. Bookstaver², Kristina Stephens^1,2, Gregory F. Payne^1,2 and William E. Bentley^1,2,*

¹ Institute for Bioscience and Biotechnology Research (IBBR), University of Maryland, College Park, MD 20742, USA

² Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA

Molecules 2018, 23(2), 341; https://doi.org/10.3390/molecules23020341 - 6 Feb 2018

Cited by 7 | Viewed by 4195

Abstract

This work sets out to provide a self-assembled biopolymer capsule activated with a multi-functional enzyme for localized delivery. This enzyme, SsoPox, which is a lactonase and phosphotriesterase, provides a means of interrupting bacterial communication pathways that have been shown to mediate pathogenicity. [...] Read more.

This work sets out to provide a self-assembled biopolymer capsule activated with a multi-functional enzyme for localized delivery. This enzyme, SsoPox, which is a lactonase and phosphotriesterase, provides a means of interrupting bacterial communication pathways that have been shown to mediate pathogenicity. Here we demonstrate the capability to express, purify and attach SsoPox to the natural biopolymer chitosan, preserving its activity to “neutralize” long-chain autoinducer-1 (AI-1) communication molecules. Attachment is shown via non-specific binding and by engineering tyrosine and glutamine affinity ‘tags’ at the C-terminus for covalent linkage. Subsequent degradation of AI-1, in this case N-(3-oxododecanoyl)-l-homoserine lactone (OdDHL), serves to “quench” bacterial quorum sensing (QS), silencing intraspecies communication. By attaching enzymes to pH-responsive chitosan that, in turn, can be assembled into various forms, we demonstrate device-based flexibility for enzyme delivery. Specifically, we have assembled quorum-quenching capsules consisting of an alginate inner core and an enzyme “decorated” chitosan shell that are shown to preclude bacterial QS crosstalk, minimizing QS mediated behaviors. Full article

(This article belongs to the Special Issue Design and Synthesis of Quorum-Sensing Inhibitors)

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11 pages, 1602 KiB

Open AccessArticle

Efficacy of Compounds Isolated from the Essential Oil of Artemisia lavandulaefolia in Control of the Cigarette Beetle, Lasioderma serricorne

by Jun Zhou¹, Kexing Zou¹, Wenjuan Zhang²

, Shanshan Guo², Hong Liu¹, Jiansheng Sun¹, Jigang Li¹, Dongye Huang¹, Yan Wu¹, Shushan Du^2,* and Almaz Borjigidai^3,*

¹ Technical Center of China Tobacco Guangxi Industrial Co., Ltd., Nanning 530001, Guangxi, China

² Beijing Key Laboratory of Traditional Chinese Medicine Protection and Utilization, Faculty of Geographical Science, Beijing Normal University, No. 19 Xinjiekouwai Street, Beijing 100875, China

³ College of Pharmacy, Minzu University of China, No. 27 Zhongguancun South Street, Beijing 100081, China

Molecules 2018, 23(2), 343; https://doi.org/10.3390/molecules23020343 - 7 Feb 2018

Cited by 17 | Viewed by 4875

Abstract

To develop natural product resources to control cigarette beetles (Lasioderma serricorne), the essential oil from Artemisia lavandulaefolia (Compositae) was investigated. Oil was extracted by hydrodistillation of the above-ground portion of A. lavandulaefolia and analyzed using gas chromatography-mass spectrometer (GC-MS). Extracted essential [...] Read more.

To develop natural product resources to control cigarette beetles (Lasioderma serricorne), the essential oil from Artemisia lavandulaefolia (Compositae) was investigated. Oil was extracted by hydrodistillation of the above-ground portion of A. lavandulaefolia and analyzed using gas chromatography-mass spectrometer (GC-MS). Extracted essential oil and three compounds isolated from the oil were then evaluated in laboratory assays to determine the fumigant, contact, and repellent efficacy against the stored-products’ pest, L. serricorne. The bioactive constituents from the oil extracts were identified as chamazulene (40.4%), 1,8-cineole (16.0%), and β-caryophyllene (11.5%). In the insecticidal activity assay, the adults of L. serricorne were susceptible to fumigant action of the essential oil and 1,8-cineole, with LC₅₀ values of 31.81 and 5.18 mg/L air. The essential oil, 1,8-cineole, chamazulene, and β-caryophyllene exhibited contact toxicity with LD₅₀ values of 13.51, 15.58, 15.18 and 35.52 μg/adult, respectively. During the repellency test, the essential oil and chamazulene had repellency approximating the positive control. The results indicated that chamazulene was abundant in A. lavandulaefolia essential oil and was toxic to cigarette beetles. Full article

(This article belongs to the Special Issue Biological Activity of Secondary Metabolites)

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15 pages, 453 KiB

Open AccessArticle

Weed Suppressing Potential and Isolation of Potent Plant Growth Inhibitors from Castanea crenata Sieb. et Zucc

by Phung Thi Tuyen^1,2, Tran Dang Xuan^2,*

, Truong Thi Tu Anh², Truong Mai Van², Ateeque Ahmad³

, Abdelnaser Abdelghany Elzaawely⁴

and Tran Dang Khanh⁵

¹ Faculty of Forest Resources and Environmental Management, Vietnam National University of Forestry, Xuan Mai, Hanoi 156200, Vietnam

² Graduate School for International Development and Cooperation, Hiroshima University, Higashi Hiroshima, Hiroshima 739-829, Japan

³ Chemical Engineering, CSIR, CIMAP, Kukrail Picnic Spot Road, Lucknow 226015, India

⁴ Department of Agricultural Botany, Faculty of Agriculture, Tanta University, Tanta 31527, Egypt

⁵ Department of Genetic Engineering, Agricultural Genetics Institute, Pham Van Dong Street, Hanoi 122300, Vietnam

Molecules 2018, 23(2), 345; https://doi.org/10.3390/molecules23020345 - 7 Feb 2018

Cited by 27 | Viewed by 5476

Abstract

This study isolated, determined, and quantified plant growth inhibitors in Japanese chestnut (Castanea crenata Sieb. et Zucc), a deciduous species native to Japan and Korea. In laboratory assays, C. crenata leaves showed strong inhibition on germination and seedling growth of Echinochloa crus-galli [...] Read more.

This study isolated, determined, and quantified plant growth inhibitors in Japanese chestnut (Castanea crenata Sieb. et Zucc), a deciduous species native to Japan and Korea. In laboratory assays, C. crenata leaves showed strong inhibition on germination and seedling growth of Echinochloa crus-galli (barnyardgrass), Lactuca sativa (lettuce), and Raphanus sativus (radish). Laboratory and greenhouse trials showed that leaves of C. crenata appeared as a promising material to manage weeds, especially the dicot weeds. By GC-MS and HPLC analyses, gallic, protocatechuic, p-hydroxybenzoic, caffeic, ferulic, ellagic, and cinnamic acids were identified and quantified, of which ellagic acid was present in the highest quantity (2.36 mg/g dried leaves). By column chromatography and spectral data (¹H- and ¹³C-NMR, IR, and LC-MS) analysis, a compound identified as 2α,3β,7β,23-tetrahydroxyurs-12-ene-28-oic acid (1) was purified from the methanolic leaf extract of C. crenata (0.93 mg/g dried leaves). This constituent showed potent inhibition on growth of E. crus-galli, a problematic weed in agricultural practice. The inhibition of the compound 1 (IC₅₀ = 2.62 and 0.41 mM) was >5 fold greater than that of p-hydroxybenzoic acid (IC₅₀ = 15.33 and 2.11 mM) on shoot and root growth of E. crus-galli, respectively. Results suggest that the isolated the compound 1 has potential to develop natural herbicides to manage E. crus-galli. This study is the first to isolate and identify 2α,3β,7β,23-tetrahydroxyurs-12-ene-28-oic acid in a plant and report its plant growth inhibitory potential. Full article

(This article belongs to the Collection Bioactive Compounds)

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15 pages, 1270 KiB

Open AccessArticle

Suramin-Induced Neurotoxicity: Preclinical Models and Neuroprotective Strategies

by David Von der Ahe^1,†, Petra Huehnchen^1,2,3,†

, Mustafa Balkaya⁴, Sarah Peruzzaro⁵, Matthias Endres^{1,2,3,6,7,8,*,†} and Wolfgang Boehmerle^1,2,3,†

¹ Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Klinik und Hochschulambulanz für Neurologie, Chariteplatz 1, 10117 Berlin, Germany

² Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Cluster of Excellence NeuroCure, 10117 Berlin, Germany

³ Berlin Institute of Health, Anna-Louisa-Karsch 2, 10178 Berlin, Germany

⁴ Burke-Cornell Medical Research Institute, White Plains, NY 10605, USA

⁵ Field Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mt. Pleasant, MI 48859, USA

⁶ Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Stroke Resarch Berlin, 10117 Berlin, Germany

⁷ German Center for Neurodegenerative Diseases (DZNE), 10117 Berlin, Germany

⁸ German Center for Cardiovascular Research (DZHK), Partner Site Berlin, 10117 Berlin, Germany

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 346; https://doi.org/10.3390/molecules23020346 - 7 Feb 2018

Cited by 16 | Viewed by 4576

Abstract

Suramin is a trypan blue analogon originally developed to treat protozoan infections, which was found to have diverse antitumor effects. One of the most severe side effects in clinical trials was the development of a peripheral sensory-motor polyneuropathy. In this study, we aimed [...] Read more.

Suramin is a trypan blue analogon originally developed to treat protozoan infections, which was found to have diverse antitumor effects. One of the most severe side effects in clinical trials was the development of a peripheral sensory-motor polyneuropathy. In this study, we aimed to investigate suramin-induced neuropathy with a focus on calcium (Ca²⁺) homeostasis as a potential pathomechanism. Adult C57Bl/6 mice treated with a single injection of 250 mg/kg bodyweight suramin developed locomotor and sensory deficits, which were confirmed by electrophysiological measurements showing a predominantly sensory axonal-demyelinating polyneuropathy. In a next step, we used cultured dorsal root ganglia neurons (DRGN) as an in vitro cell model to further investigate underlying pathomechanisms. Cell viability of DRGN was significantly decreased after 24-hour suramin treatment with a calculated IC₅₀ of 283 µM. We detected a suramin-induced Ca²⁺ influx into DRGN from the extracellular space, which could be reduced with the voltage-gated calcium channel (VGCC) inhibitor nimodipine. Co-incubation of suramin and nimodipine partially improved cell viability of DRGN after suramin exposure. In summary, we describe suramin-induced neurotoxic effects on DRGN as well as potentially neuroprotective agents targeting intracellular Ca²⁺ dyshomeostasis. Full article

(This article belongs to the Special Issue Neuroprotective Agents)

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15 pages, 6444 KiB

Open AccessArticle

Design, Synthesis, and Biological Evaluation of 2-(Benzylamino-2-Hydroxyalkyl)Isoindoline-1,3-Diones Derivatives as Potential Disease-Modifying Multifunctional Anti-Alzheimer Agents

by Dawid Panek^1,†, Anna Więckowska^1,†

, Anna Pasieka¹, Justyna Godyń¹, Jakub Jończyk¹, Marek Bajda¹, Damijan Knez²

, Stanislav Gobec² and Barbara Malawska^1,*

¹ Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland

² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 347; https://doi.org/10.3390/molecules23020347 - 7 Feb 2018

Cited by 27 | Viewed by 5887

Abstract

The complex nature of Alzheimer’s disease calls for multidirectional treatment. Consequently, the search for multi-target-directed ligands may lead to potential drug candidates. The aim of the present study is to seek multifunctional compounds with expected activity against disease-modifying and symptomatic targets. A series [...] Read more.

The complex nature of Alzheimer’s disease calls for multidirectional treatment. Consequently, the search for multi-target-directed ligands may lead to potential drug candidates. The aim of the present study is to seek multifunctional compounds with expected activity against disease-modifying and symptomatic targets. A series of 15 drug-like various substituted derivatives of 2-(benzylamino-2-hydroxyalkyl)isoindoline-1,3-diones was designed by modification of cholinesterase inhibitors toward β-secretase inhibition. All target compounds have been synthesized and tested against eel acetylcholinesterase (eeAChE), equine serum butyrylcholinesterase (eqBuChE), human β-secretase (hBACE-1), and β-amyloid (Aβ-aggregation). The most promising compound, 12 (2-(5-(benzylamino)-4-hydroxypentyl)isoindoline-1,3-dione), displayed inhibitory potency against eeAChE (IC₅₀ = 3.33 μM), hBACE-1 (43.7% at 50 μM), and Aβ-aggregation (24.9% at 10 μM). Molecular modeling studies have revealed possible interaction of compound 12 with the active sites of both enzymes—acetylcholinesterase and β-secretase. In conclusion: modifications of acetylcholinesterase inhibitors led to the discovery of a multipotent anti-Alzheimer’s agent, with moderate and balanced potency, capable of inhibiting acetylcholinesterase, a symptomatic target, and disease-modifying targets: β-secretase and Aβ-aggregation. Full article

(This article belongs to the Special Issue Novel Multifunctional Ligands and Their Application in Alzheimer's Disease)

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9 pages, 1096 KiB

Open AccessArticle

Norisoprenoids from the Brown Alga Sargassum naozhouense Tseng et Lu

by Yan Peng^1,2

, Ri-Ming Huang³, Xiu-Ping Lin² and Yong-Hong Liu^2,4,5,*

¹ Life Science and Technology School, Lingnan Normal University, Cunjin Road 29, Zhanjiang 524048, China

² Key Laboratory of Tropical Marine Bio-Resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Xinggang West Road 164, Guangzhou 510301, China

³ Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Wushan Road 483, Guangzhou 510642, China

⁴ University of Chinese Academy of Sciences, Yuquan Road 19(A), Beijing 100049, China

⁵ South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center, Xinggang West Road 164, Guangzhou 510301, China

Molecules 2018, 23(2), 348; https://doi.org/10.3390/molecules23020348 - 7 Feb 2018

Cited by 23 | Viewed by 3647

Abstract

A new C₁₁-norisoprenoid derivative, sargassumone (1), has been isolated from Sargassum naozhouense together with six known norisoprenoids and a highly oxygenated cyclopentene: (2R,6S,8S,9S)-hexahydro-2,9-dihydroxy-4,4,8-trimethyl-6-acetyloxy-3(2H)-benzofuranone (2), (6S,8 [...] Read more.

A new C₁₁-norisoprenoid derivative, sargassumone (1), has been isolated from Sargassum naozhouense together with six known norisoprenoids and a highly oxygenated cyclopentene: (2R,6S,8S,9S)-hexahydro-2,9-dihydroxy-4,4,8-trimethyl-6-acetyloxy-3(2H)-benzofuranone (2), (6S,8S,9R)-hexahydro-6,9-dihydroxy-4,4,8-trimethyl-2(2H)-benzofuranone (3), (6S,8S,9R)-hexahydro-6,9-dihydroxy-4,4,8-trimethyl-2(2H)-benzofuranone (4), loliolide (5), (+)-epiloliolide (6), spheciospongones A (7), and (+)-kjellmanianone (8). Compound 1 was identified on the basis of nuclear magnetic resonance (NMR) and mass spectrometry (MS) analysis, and the absolute stereochemistry was defined by NOESY spectroscopy, minimizing energy calculation, and circular dichroism (CD) spectra. The known compounds 2–8, isolated from S. naozhouense for the first time, were identified by comparison of their physical and spectroscopic data with those reported in the literature. Compound 6 was tested for its inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), antioxidant activity with 1,1-diphyl-2-picrylhydrazyl (DPPH) free radicals, and antimicrobial activity against resistant clinical isolates of Candida albicans, methicillin-resistant Staphylococcus aureus (MRSA), and Escherichia coli. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 970 KiB

Open AccessArticle

Effects of Phytochemical P-Glycoprotein Modulators on the Pharmacokinetics and Tissue Distribution of Doxorubicin in Mice

by Tae Hwan Kim^1,†

, Soyoung Shin^2,†

, Sun Dong Yoo³ and Beom Soo Shin^3,*

¹ College of Pharmacy, Catholic University of Daegu, Gyeongsan 38430, Gyeongbuk, Korea

² College of Pharmacy, Wonkwang University, Iksan 54538, Jeonbuk, Korea

³ School of Pharmacy, Sungkyunkwan University, Suwon 16419, Gyeonggi-do, Korea

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 349; https://doi.org/10.3390/molecules23020349 - 7 Feb 2018

Cited by 23 | Viewed by 4425

Abstract

Pungent spice constituents such as piperine, capsaicin and [6]-gingerol consumed via daily diet or traditional Chinese medicine, have been reported to possess various pharmacological activities. These dietary phytochemicals have also been reported to inhibit P-glycoprotein (P-gp) in vitro and act as an alternative [...] Read more.

Pungent spice constituents such as piperine, capsaicin and [6]-gingerol consumed via daily diet or traditional Chinese medicine, have been reported to possess various pharmacological activities. These dietary phytochemicals have also been reported to inhibit P-glycoprotein (P-gp) in vitro and act as an alternative to synthetic P-gp modulators. However, the in vivo effects on P-gp inhibition are currently unknown. This study aimed to test the hypothesis that phytochemical P-gp inhibitors, i.e., piperine, capsaicin and [6]-gingerol, modulate the in vivo tissue distribution of doxorubicin, a representative P-gp substrate. Mice were divided into four groups and each group was pretreated with intraperitoneal injections of control vehicle, piperine, capsaicin, or [6]-gingerol and doxorubicin (1 mg/kg) was administered via the penile vein. The concentrations of the phytochemicals and doxorubicin in the plasma and tissues were determined by LC-MS/MS. The overall plasma concentration-time profiles of doxorubicin were not significantly affected by piperine, capsaicin, or [6]-gingerol. In contrast, doxorubicin accumulation was observed in tissues pretreated with piperine or capsaicin. The tissue to plasma partition coefficients, K_p, for the liver and kidney were higher in the piperine-pretreated group, while the K_p for kidney, brain and liver were higher in the capsaicin-pretreated group. [6]-Gingerol did not affect doxorubicin tissue distribution. The data demonstrated that the phytochemicals modulated doxorubicin tissue distribution, which suggested their potential to induce food-drug interactions and act as a strategy for the delivery of P-gp substrate drugs to target tissues and tumors. Full article

(This article belongs to the Section Natural Products Chemistry)

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16 pages, 2122 KiB

Open AccessArticle

The Reaction of Oxy Hemoglobin with Nitrite: Mechanism, Antioxidant-Modulated Effect, and Implications for Blood Substitute Evaluation

by Denisa Hathazi¹, Florina Scurtu¹, Cristina Bischin¹, Augustin Mot¹, Amr A. A. Attia^1,2, Jacob Kongsted² and Radu Silaghi-Dumitrescu^1,*

¹ Department of Chemistry, Faculty of Chemistry and Chemical Engineering, Babeş-Bolyai University, 11 Arany Janos Street, 400028 Cluj-Napoca, Romania

² Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark

Molecules 2018, 23(2), 350; https://doi.org/10.3390/molecules23020350 - 7 Feb 2018

Cited by 28 | Viewed by 5384

Abstract

The autocatalytic reaction between nitrite and the oxy form of globins involves free radicals. For myoglobin (Mb), an initial binding of nitrite to the iron-coordinated oxygen molecule was proposed; the resulting ferrous-peroxynitrate species was not detected, but its decay product, the high-valent ferryl [...] Read more.

The autocatalytic reaction between nitrite and the oxy form of globins involves free radicals. For myoglobin (Mb), an initial binding of nitrite to the iron-coordinated oxygen molecule was proposed; the resulting ferrous-peroxynitrate species was not detected, but its decay product, the high-valent ferryl form, was demonstrated in stopped-flow experiments. Reported here are the stopped flow spectra recorded upon mixing oxy Hb (native, as well as chemically-derivatized in the form of several candidates of blood substitutes) with a supraphysiological concentration of nitrite. The data may be fitted to a simple kinetic model involving a transient met-aqua form, in contrast to the ferryl detected in the case of Mb in a similar reaction sequence. These data are in line with a previous observation of a transient accumulation of ferryl Hb under auto-catalytic conditions at much lower concentrations of nitrite (Grubina, R. et al. J. Biol. Chem. 2007, 282, 12916). The simple model for fitting the stopped-flow data leaves a small part of the absorbance changes unaccounted for, unless a fourth species is invoked displaying features similar to the oxy and tentatively assigned as ferrous-peroxynitrate. Density functional theory (DFT) calculations support this latter assignment. The reaction allows for differentiating between the reactivities of various chemically modified hemoglobins, including candidates for blood substitutes. Polymerization of hemoglobin slows the nitrite-induced oxidation, in sharp contrast to oxidative-stress type reactions which are generally accelerated, not inhibited. Sheep hemoglobin is found to be distinctly more resistant to reaction with nitrite compared to bovine Hb, at large nitrite concentrations (stopped-flow experiments directly observing the oxy + nitrite reaction) as well as under auto-catalytic conditions. Copolymerization of Hb with bovine serum albumin (BSA) using glutaraldehyde leads to a distinct increase of the lag time compared to native Hb as well as to any other form of derivatization examined in the present study. The Hb-BSA copolymer also displays a slower initial reaction with nitrite under stopped-flow conditions, compared to native Hb. Full article

(This article belongs to the Section Inorganic Chemistry)

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13 pages, 5218 KiB

Open AccessArticle

Exploring Protein Cavities through Rigidity Analysis

by Stephanie Mason¹, Brian Y. Chen² and Filip Jagodzinski^1,*

¹ Department of Computer Science, Western Washington University, 516 High Street, Bellingham, WA 98225, USA

² Department of Computer Science and Engineering, Lehigh University, 19 Memorial Drive West, Bethlehem, PA 18015, USA

Molecules 2018, 23(2), 351; https://doi.org/10.3390/molecules23020351 - 7 Feb 2018

Cited by 6 | Viewed by 4293

Abstract

The geometry of cavities in the surfaces of proteins facilitates a variety of biochemical functions. To better understand the biochemical nature of protein cavities, the shape, size, chemical properties, and evolutionary nature of functional and nonfunctional surface cavities have been exhaustively surveyed in [...] Read more.

The geometry of cavities in the surfaces of proteins facilitates a variety of biochemical functions. To better understand the biochemical nature of protein cavities, the shape, size, chemical properties, and evolutionary nature of functional and nonfunctional surface cavities have been exhaustively surveyed in protein structures. The rigidity of surface cavities, however, is not immediately available as a characteristic of structure data, and is thus more difficult to examine. Using rigidity analysis for assessing and analyzing molecular rigidity, this paper performs the first survey of the relationships between cavity properties, such as size and residue content, and how they correspond to cavity rigidity. Our survey measured a variety of rigidity metrics on 120,323 cavities from 12,785 sequentially non-redundant protein chains. We used VASP-E, a volume-based algorithm for analyzing cavity geometry. Our results suggest that rigidity properties of protein cavities are dependent on cavity surface area. Full article

(This article belongs to the Special Issue Selected Papers from the 10th Computational Structural Bioinformatics Workshop (CSBW-2017))

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17 pages, 3796 KiB

Open AccessArticle

Hepatoprotective Effects of a Functional Formula of Three Chinese Medicinal Herbs: Experimental Evidence and Network Pharmacology-Based Identification of Mechanism of Action and Potential Bioactive Components

by Sha Li¹, Ning Wang^1,2, Ming Hong¹, Hor-Yue Tan¹, Guofeng Pan^1,3 and Yibin Feng^1,2,*

¹ School of Chinese Medicine, The University of Hong Kong, Hong Kong, China

² Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen 518057, China

³ Beijing Shijitang Hospital, Capital Medical University, Beijing 100069, China

Molecules 2018, 23(2), 352; https://doi.org/10.3390/molecules23020352 - 7 Feb 2018

Cited by 36 | Viewed by 7793

Abstract

Various Chinese herbal medicines (CHMs) have shown beneficial liver protection effects. Jian-Gan-Bao (JGB), a functional herbal formula, consists of three famous CHMs, including Coriolus versicolor, Salvia miltiorrhiza and Schisandra chinensis, which has been used as a folk medicine for several chronic [...] Read more.

Various Chinese herbal medicines (CHMs) have shown beneficial liver protection effects. Jian-Gan-Bao (JGB), a functional herbal formula, consists of three famous CHMs, including Coriolus versicolor, Salvia miltiorrhiza and Schisandra chinensis, which has been used as a folk medicine for several chronic liver diseases. In the present study, we aim systemically to evaluate the effects of JGB on acute and chronic alcoholic liver diseases (ALD) as well as non-alcoholic fatty liver disease (NAFLD) in mouse models, and identify its potential bioactive components and mechanism of action. JGB showed preventive effects for acute and chronic ALD as well as NAFLD, while post-treatment of JGB showed no significant effect, suggesting the nature of JGB as a health supplement rather than a drug. Furthermore, a compound-target network was constructed to identify the potential bioactive compounds and pathways that regulate its hepatoprotective effects. There are 40 bioactive compounds and 15 related targets that have been identified via this network pharmacology study. Among them are miltirone, neocryptotanshinone II and deoxyshikonin, with desirable pharmaceutical properties. Pathways relating to inflammation, fatty acid oxidation, tumor necrosis factor (TNF) production and cell proliferation were predicted as bioactive compounds and potential underlying mechanisms, which should be the focus of study in this field in the future. Full article

(This article belongs to the Collection Herbal Medicine Research)

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14 pages, 3333 KiB

Open AccessArticle

VSpipe, an Integrated Resource for Virtual Screening and Hit Selection: Applications to Protein Tyrosine Phospahatase Inhibition

by Sandra Álvarez-Carretero^1,2, Niki Pavlopoulou^1,3, James Adams¹, Jane Gilsenan¹ and Lydia Tabernero^1,*

¹ School of Biological Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UK

² School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, UK

³ Insight Centre for Data Analytics, NUIG, Galway H91, Ireland

Molecules 2018, 23(2), 353; https://doi.org/10.3390/molecules23020353 - 7 Feb 2018

Cited by 12 | Viewed by 5677

Abstract

The use of computational tools for virtual screening provides a cost-efficient approach to select starting points for drug development. We have developed VSpipe, a user-friendly semi-automated pipeline for structure-based virtual screening. VSpipe uses the existing tools AutoDock and OpenBabel together with software developed [...] Read more.

The use of computational tools for virtual screening provides a cost-efficient approach to select starting points for drug development. We have developed VSpipe, a user-friendly semi-automated pipeline for structure-based virtual screening. VSpipe uses the existing tools AutoDock and OpenBabel together with software developed in-house, to create an end-to-end virtual screening workflow ranging from the preparation of receptor and ligands to the visualisation of results. VSpipe is efficient and flexible, allowing the users to make choices at different steps, and it is amenable to use in both local and cluster mode. We have validated VSpipe using the human protein tyrosine phosphatase PTP1B as a case study. Using a combination of blind and targeted docking VSpipe identified both new and known functional ligand binding sites. Assessment of different binding clusters using the ligand efficiency plots created by VSpipe, defined a drug-like chemical space for development of PTP1B inhibitors with potential applications to other PTPs. In this study, we show that VSpipe can be deployed to identify and compare different modes of inhibition thus guiding the selection of initial hits for drug discovery. Full article

(This article belongs to the Special Issue Protein-Tyrosine Phosphatase Inhibitors)

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20 pages, 2703 KiB

Open AccessArticle

Stability of Anthocyanins and Their Degradation Products from Cabernet Sauvignon Red Wine under Gastrointestinal pH and Temperature Conditions

by Ping Yang^1,†, Chunlong Yuan^1,2,3,†, Hua Wang^1,2,3,*, Fuliang Han^1,2,3,*, Yangjie Liu¹, Lin Wang¹ and Yang Liu¹

¹ College of Enology, Northwest A&F University, Yangling 712100, China

² Shaanxi Engineering Research Center for Viti-Viniculture, Northwest A&F University, Yangling 712100, China

³ Heyang Viticulture Experimental Station, Northwest A&F University, Heyang 715300, China

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 354; https://doi.org/10.3390/molecules23020354 - 7 Feb 2018

Cited by 80 | Viewed by 6457

Abstract

This study investigated the stability of wine anthocyanins under simulated gastrointestinal pH and temperature conditions, and further studied the evolution of anthocyanin degradation products through simulated digestive conditions. The aim of this study was to investigate the relation between anthocyanins’ structure and their [...] Read more.

This study investigated the stability of wine anthocyanins under simulated gastrointestinal pH and temperature conditions, and further studied the evolution of anthocyanin degradation products through simulated digestive conditions. The aim of this study was to investigate the relation between anthocyanins’ structure and their digestive stability. Results showed that a total of 22 anthocyanins were identified in wine and most of these anthocyanins remained stable under simulated gastric digestion process. However, a dramatic concentration decrease happened to these anthocyanins during simulated intestinal digestion. The stability of anthocyanins in digestive process appeared to be related to their structure. The methoxy group in the B-ring enhanced the stability of anthocyanins, whereas hydroxyl group resulted in a reduction of their stability. Acylation decreased the stability of malvidin 3-O-glucoside. Pyruvic acid conjugation enhanced the structural stability of pyranoanthocyanins, whereas acetaldehyde attachment weakened their stability. A commercial malvidin 3-O-glucoside standard was used to investigate anthocyanin degradation products under simulated digestion process, and syringic acid, protocatechuic acid and vanillic acid were confirmed to be the degradation products via anthocyanin chalcone conversion path. Gallic acid, protocatechuic acid, vanillic acid, syringic acid, and p-coumaric acid in wine experienced a significant concentration decrease during digestion process. However, wine model solution revealed that phenolic acids remained stable under gastrointestinal conditions, except gallic acid. Full article

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8 pages, 621 KiB

Open AccessFeature PaperCommunication

Bauerenol Acetate, the Pentacyclic Triterpenoid from Tabernaemontana longipes, is an Antitrypanosomal Agent

by Simira Carothers¹, Rogers Nyamwihura¹, Jasmine Collins¹, Huaisheng Zhang¹, HaJeung Park², William N. Setzer³

and Ifedayo Victor Ogungbe^1,*

¹ Department of Chemistry, Jackson State University, Jackson, MS 39217, USA

² X-ray Crystallography Laboratory, Scripps Research Institute-FL, Jupiter, FL 33458, USA

³ Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA

Molecules 2018, 23(2), 355; https://doi.org/10.3390/molecules23020355 - 8 Feb 2018

Cited by 8 | Viewed by 4645

Abstract

The Latin American plant Tabernaemontana longipes was studied in this work as a potential source of antiparasitic agents. The chloroform extract of T. longipes leaves was separated into several fractions, and tested for antitrypanosomal activity. One of the fractions displayed significant growth inhibitory [...] Read more.

The Latin American plant Tabernaemontana longipes was studied in this work as a potential source of antiparasitic agents. The chloroform extract of T. longipes leaves was separated into several fractions, and tested for antitrypanosomal activity. One of the fractions displayed significant growth inhibitory activity against Trypanosoma brucei. The active principle in the fraction was isolated, purified, and characterized by NMR and mass spectrometry. The antitrypanosomal agent in the CHCl₃ extract of T. longipes leaves is the pentacyclic triterpenoid bauerenol acetate. A metabolite profiling assay suggest that the triterpenoid influences cholesterol metabolism. The molecular target(s) of bauerenol and its acetate, like many other antiparasitic pentacyclic triterpenoids is/are unknown, but they present privileged structural scaffolds that can be explored for structure-based activity optimization studies using phenotypic assays. Full article

(This article belongs to the Collection Natural Products as Leads or Drugs against Neglected Tropical Diseases)

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12 pages, 3004 KiB

Open AccessArticle

High Add Valued Application of Turpentine in Crop Production through Structural Modification and QSAR Analysis

by Yanqing Gao^1,†, Jingjing Li^2,†, Jian Li^2,*, Zhanqian Song³, Shibin Shang³ and Xiaoping Rao³

¹ Research & Development Center of Biorational Pesticide, College of Plant Protection, Northwest A&F University, Yangling 712100, Shaanxi, China

² Shaanxi Province Key Laboratory of Economic Plant Resources Development and Utilization, College of Forestry, Northwest A&F University, Yangling 712100, Shaanxi, China

³ Institute of Chemical Industry of Forest Products, Chinese Academy of Forestry, Nanjing 210042, Jiangsu, China

^† These authors contributed equally to this paper and share co-first authorship.

Molecules 2018, 23(2), 356; https://doi.org/10.3390/molecules23020356 - 8 Feb 2018

Cited by 14 | Viewed by 5131

Abstract

Turpentine is a volatile component of resin, which is an abundant forest resource in Southern China. As one of the most important components, the integrated application of β-pinene has been studied. The broad-spectrum evaluation of β-pinene and its analogues has, therefore, been necessary. [...] Read more.

Turpentine is a volatile component of resin, which is an abundant forest resource in Southern China. As one of the most important components, the integrated application of β-pinene has been studied. The broad-spectrum evaluation of β-pinene and its analogues has, therefore, been necessary. In an attempt to expand the scope of agro-activity trials, the preparation and the evaluation of the herbicidal activity of a series of β-pinene analogues against three agricultural herbs were carried out. In accordance with the overall herbicidal activity, it is noteworthy that compounds 6k, 6l, and 6m demonstrated extreme activity with IC₅₀ values of 0.065, 0.065, and 0.052 mol active ingredients/hectare against E. crus-galli. The preliminary structure–activity relationship (SAR) was analyzed and the compounds with the appropriate volatility and substituent type that had beneficial herbicidal activity were analyzed. Simultaneously, the quantitative structure–activity relationship (QSAR) model was built and the most important structural features were indicated, which was, to a certain extent, in line with the SAR study. The study aimed to study the application of the forest resource turpentine in agriculture as a potential and alternative approach for comprehensive utilization. Full article

(This article belongs to the Collection Recent Advances in Flavors and Fragrances)

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9 pages, 372 KiB

Open AccessArticle

Development of Volatile Compounds during Hydrolysis of Porcine Hemoglobin with Papain

by Kathrine Holmgaard Bak^1,*

, Mikael Agerlin Petersen¹

, René Lametsch¹, Erik T. Hansen² and Jorge Ruiz-Carrascal¹

¹ Department of Food Science, University of Copenhagen, Rolighedsvej 26, 1958 Frederiksberg C, Denmark

² Danish Crown Ingredients, Flæsketorvet 41, 1711 Copenhagen V, Denmark

Molecules 2018, 23(2), 357; https://doi.org/10.3390/molecules23020357 - 8 Feb 2018

Cited by 19 | Viewed by 4082

Abstract

There is a growing market for the use of hydrolysates from animal side-streams for production of high-protein supplements. However, there can be issues with development of off-flavors, either due to the raw material in question or due to the hydrolysis process itself. This [...] Read more.

There is a growing market for the use of hydrolysates from animal side-streams for production of high-protein supplements. However, there can be issues with development of off-flavors, either due to the raw material in question or due to the hydrolysis process itself. This study examined the development of volatile compounds during hydrolysis of hemoglobin. Briefly, porcine hemoglobin was hydrolyzed by 0.5% papain for up to 5 h, and the development of volatile compounds was analyzed via gas chromatography-mass spectrometry. The results showed that there was significant development of a number of volatile compounds with time, e.g., certain Maillard reaction and lipid oxidation products, which are likely candidates for the aroma development during hydrolysis. Furthermore, it was shown that development of a number of the volatiles was due to the hydrolysis process, as these compounds were not found in a control without enzyme. Full article

(This article belongs to the Collection Recent Advances in Flavors and Fragrances)

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15 pages, 20769 KiB

Open AccessArticle

Antifungal Activity of Natural Volatile Organic Compounds against Litchi Downy Blight Pathogen Peronophythora litchii

by Mengyu Xing^1,2, Li Zheng^1,3, Yizhen Deng¹, Dandan Xu¹, Pinggen Xi¹, Minhui Li¹, Guanghui Kong¹ and Zide Jiang^1,*

¹ Department of Plant Pathology/Guangdong Province Key Laboratory of Microbial Signals and Disease Control, South China Agricultural University, Guangzhou 510642, China

² Institute of Tropical Agriculture and Forestry, Hainan University, Haikou 570228, China

³ Chinese Academy of Tropical Agricultural Sciences Guangzhou Experimental Station, Guangzhou 510140, China

Molecules 2018, 23(2), 358; https://doi.org/10.3390/molecules23020358 - 8 Feb 2018

Cited by 63 | Viewed by 5864

Abstract

Litchi (Litchi chinensis Sonn.) is a commercially important fruit but its production and quality are restricted by litchi downy blight, caused by the oomycete pathogen Peronophythora litchii Chen. Volatile substances produced by a biocontrol antinomycetes Streptomyces fimicarius BWL-H1 could inhibited P. litchii [...] Read more.

Litchi (Litchi chinensis Sonn.) is a commercially important fruit but its production and quality are restricted by litchi downy blight, caused by the oomycete pathogen Peronophythora litchii Chen. Volatile substances produced by a biocontrol antinomycetes Streptomyces fimicarius BWL-H1 could inhibited P. litchii growth and development both in vitro and in detached litchi leaf and fruit infection assay. Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM) analyses indicated that volatile organic compounds (VOCs) from BWL-H1 resulted in severe damage to the endomembrane system and cell wall of P. litchii cells in vitro and abnormal morphology of appressoria, as well as deformed new hyphae in infection process. VOCs could suppress mycelial growth, sporulation, while with no obvious effect on sporangia germination. Based on gas chromatography-mass spectrophotometric analyses, 32 VOCs were identified from S. fimicarius BWL-H1, the most abundant of which was phenylethyl alcohol. Eight VOCs, including phenylethyl alcohol, ethyl phenylacetate, methyl anthranilate, α-copaene, caryophyllene, humulene, methyl salicylate and 4-ethylphenol, that are commercially available, were purchased and their bioactivity was tested individually. Except for humulene, the other seven tested volatile compounds shown strong inhibitory activity against mycelial growth, sporulation, sporangia germination and germ-tube growth of P. litchii. Especially, 4-ethylphenol showed the highest inhibitory effect on sporulation at a very low concentration of 2 µL/L. Overall, our results provided a better understanding of the mode of action of volatiles from BWL-H1 on P. litchii, and showed that volatiles from BWL-H1 have the potential for control of postharvest litchi downy blight. Full article

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12 pages, 2551 KiB

Open AccessCommunication

Comparative Evaluation of Soluble and Insoluble-Bound Phenolics and Antioxidant Activity of Two Chinese Mistletoes

by Qing Li¹, Shihua Yang², Yongqiang Li^1,*

, Xiaofeng Xue^3,*, Yonghua Huang¹, Hengguo Luo¹, Yiming Zhang¹ and Zhichao Lu¹

¹ College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China

² College of Foreign Languages, Yunnan Agricultural University, Kunming 650201, China

³ Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing 100093, China

Molecules 2018, 23(2), 359; https://doi.org/10.3390/molecules23020359 - 8 Feb 2018

Cited by 36 | Viewed by 4076

Abstract

Mistletoes are used medicinally in order to treat various human illnesses. Few studies have reported on the phenolic content and antioxidant properties of Chinese mistletoes (CMs). In this work, the total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activities of soluble [...] Read more.

Mistletoes are used medicinally in order to treat various human illnesses. Few studies have reported on the phenolic content and antioxidant properties of Chinese mistletoes (CMs). In this work, the total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activities of soluble and insoluble-bound phenolic extracts from CMs hosted by Camellia assamica (Mast.) Chang (CMC) and Pyrus, i, f. (CMP) were compared. Phenolic compounds in CMC and CMP were identified and quantified using high-performance liquid chromatography (HPLC). The results indicated that the TPC of soluble phenolic extracts was higher than insoluble-bound phenolic counterparts in both CMC and CMP. In addition, the TPC of soluble, insoluble-bound and total phenolic fractions (9.91 ± 0.23, 4.59 ± 0.27 and 14.50 ± 0.35 μmol ferulic acid equivalents per gram (FAE/g) dry sample) extracted from CMP were higher than those extracted from CMC. The soluble phenolic extracts in CMP showed higher antioxidant activities than those in CMC. Eighteen phenolic compounds from soluble and insoluble-bound phenolic extracts from the CMs were identified and quantified by HPLC. This study indicates that CMC and CMP, especially the latter, could be sources of antioxidants in human health care. Full article

(This article belongs to the Special Issue Extractable and Non-Extractable Antioxidants)

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9 pages, 1145 KiB

Open AccessFeature PaperArticle

Chemoselective Polymerization of Polar Divinyl Monomers with Rare-Earth/Phosphine Lewis Pairs

by Pengfei Xu¹, Lei Wu¹, Liqiu Dong^1,2 and Xin Xu^1,*

¹ Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China

² Suzhou International Academy, BFSU, Suzhou 215200, China

Molecules 2018, 23(2), 360; https://doi.org/10.3390/molecules23020360 - 8 Feb 2018

Cited by 26 | Viewed by 5737

Abstract

This work reports the chemoselective polymerization of polar divinyl monomers, including allyl methacrylate (AMA), vinyl methacrylate (VMA), and 4-vinylbenzyl methacrylate (VBMA), by using simple Lewis pairs comprised of homoleptic rare-earth (RE) aryloxide complexes RE(OAr)₃ (RE = Sc (1), Y ( [...] Read more.

This work reports the chemoselective polymerization of polar divinyl monomers, including allyl methacrylate (AMA), vinyl methacrylate (VMA), and 4-vinylbenzyl methacrylate (VBMA), by using simple Lewis pairs comprised of homoleptic rare-earth (RE) aryloxide complexes RE(OAr)₃ (RE = Sc (1), Y (2), Sm (3), La (4), Ar = 2,6-tBu₂C₆H₃) and phosphines PR₃ (R = Ph, Cy, Et, Me). Catalytic activities of polymerizations relied heavily upon the cooperation of Lewis acid and Lewis base components. The produced polymers were soluble in common organic solvents and often had a narrow molecular weight distribution. A highly syndiotactic poly(allyl methacrylate) (PAMA) with rr ~88% could be obtained by the scandium complex 1/PEt₃ pair at −30 °C. In the case of poly(4-vinylbenzyl methacrylate) (PVBMA), it could be post-functionalized with PhCH₂SH. Mechanistic study, including the isolation of the zwitterionic active species and the end-group analysis, revealed that the frustrated Lewis pair (FLP)-type addition was the initiating step in the polymerization. Full article

(This article belongs to the Special Issue Lewis Pair Polymerization for New Reactivity and Structure in Polymer Synthesis)

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17 pages, 2031 KiB

Open AccessArticle

Antibacterial Activities of Azole Complexes Combined with Silver Nanoparticles

by Nestor J. Bello-Vieda¹

, Homero F. Pastrana²

, Manuel F. Garavito³, Alba G. Ávila², Adriana M. Celis³

, Alvaro Muñoz-Castro⁴, Silvia Restrepo³ and John J. Hurtado^1,*

¹ Department of Chemistry, Universidad de los Andes, Carrera 1 No. 18A-12, Bogotá 111711, Colombia

² Eléctrica y Electrónica, Centro de Microelectrónica, Universidad de Los Andes, Carrera 1 No. 18A-12, Bogotá 111711, Colombia

³ Laboratorio de Micología y Fitopatología, Departamento de Ciencias Biológicas, Universidad de Los Andes, Carrera 1 No. 18A-12, Bogotá 111711, Colombia

⁴ Grupo de Química Inorgánica y Materiales Moleculares, Universidad Autonoma de Chile, El Llano Subercaseaux 2801, Santiago, Chile

Molecules 2018, 23(2), 361; https://doi.org/10.3390/molecules23020361 - 8 Feb 2018

Cited by 36 | Viewed by 4510

Abstract

Growing antimicrobial resistance is considered a potential threat for human health security by health organizations, such as the WHO, CDC and FDA, pointing to MRSA as an example. New antibacterial drugs and complex derivatives are needed to combat the development of bacterial resistance. [...] Read more.

Growing antimicrobial resistance is considered a potential threat for human health security by health organizations, such as the WHO, CDC and FDA, pointing to MRSA as an example. New antibacterial drugs and complex derivatives are needed to combat the development of bacterial resistance. Six new copper and cobalt complexes of azole derivatives were synthesized and isolated as air-stable solids and characterized by melting point analyses, elemental analyses, thermogravimetric analyses (TGA), and infrared and ultraviolet/visible spectroscopy. The analyses and spectral data showed that the complexes had 1:1 (M:L) stoichiometries and tetrahedral geometries, the latter being supported by DFT calculations. The antibacterial activities of the metal complexes by themselves and combined with silver nanoparticles (AgNPs; 2 μg mL⁻¹) were assessed in vitro by broth microdilution assays against eight bacterial strains of clinical relevance. The results showed that the complexes alone exhibited moderate antibacterial activities. However, when the metal complexes were combined with AgNPs, their antibacterial activities increased (up to 10-fold in the case of complex 5), while human cell viabilities were maintained. The minimum inhibitory concentration (MIC₅₀) values were in the range of 25–500 μg mL⁻¹. This study thus presents novel approaches for the design of materials for fighting bacterial resistance. The use of azole complexes combined with AgNPs provides a new alternative against bacterial infections, especially when current treatments are associated with the rapid development of antibiotic resistance. Full article

(This article belongs to the Section Inorganic Chemistry)

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10 pages, 2900 KiB

Open AccessArticle

Coordination-Enhanced Luminescence on Tetra-Phenylethylene-Based Supramolecular Assemblies

by Qian-Qian Yan^1,2, Shao-Jun Hu^1,2, Guang-Lu Zhang², Ting Zhang², Li-Peng Zhou² and Qing-Fu Sun^2,*

¹ College of Chemistry, Fuzhou University, Fuzhou 350108, China

² State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, China

Molecules 2018, 23(2), 363; https://doi.org/10.3390/molecules23020363 - 9 Feb 2018

Cited by 7 | Viewed by 5752

Abstract

Materials with aggregation-induced emission (AIE) properties have received increased attention recently due to their potential applications in light-emitting devices, chemo/biosensors and biomedical diagnostics. In general, AIE requires the forced aggregation of the AIEgens induced by the poor solvent or close arrangement of AIEgens [...] Read more.

Materials with aggregation-induced emission (AIE) properties have received increased attention recently due to their potential applications in light-emitting devices, chemo/biosensors and biomedical diagnostics. In general, AIE requires the forced aggregation of the AIEgens induced by the poor solvent or close arrangement of AIEgens covalently attached to polymer chains. Here, we report two coordination-enhanced fluorescent supramolecular complexes featuring hierarchically restricted intramolecular motions via the self-assembly of tetraphenylethylene (TPE)-based tetra-dentate (L^a) and bidentate (L^b) ligands and the cis-Pd(en)(NO₃)₂ (en = ethylenediamine) unit. While the free ligands are non-emissive in dilute solution and show typical AIE properties in both mixed solvent system and the solid state, the self-assembled complexes maintain their fluorescent nature in the solution state. In particular, the Pd₄(L^a)₂ complex shows remarkable 6-fold fluorescent enhancement over L^a in dilute solution. We anticipate that these kinds of coordination-enhanced emissive supramolecules will find applications in biomedical sensing or labeling. Full article

(This article belongs to the Special Issue Supramolecular Chemistry and Self-Assembly: Themed Issue in Honor of Professor Itamar Willner on the Occasion of His 70th Birthday)

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10 pages, 6426 KiB

Open AccessArticle

High Catalytic Efficiency of Nanostructured β-CoMoO₄ in the Reduction of the Ortho-, Meta- and Para-Nitrophenol Isomers

by Fahd Al-Wadaani¹, Ahmed Omer¹, Mostafa Abboudi¹

, Hicham Oudghiri Hassani^1,2,*, Souad Rakass¹, Mouslim Messali¹ and Mohammed Benaissa³

¹ Chemistry Department, College of Science, Taibah University, Almadinah 30002, Saudi Arabia

² Département Sciences de la Nature, Cégep de Drummondville, 960 Rue Saint-Georges, Drummondville, QC J2C 6A2, Canada

³ LMPHE, Département de Physique, Faculté des Sciences, Université Mohammed V, B.P. 1014 RP, Rabat 10000, Morocco

Molecules 2018, 23(2), 364; https://doi.org/10.3390/molecules23020364 - 9 Feb 2018

Cited by 20 | Viewed by 5938

Abstract

Nanostructured β-CoMoO₄ catalysts have been prepared via the thermal decomposition of an oxalate precursor. The catalyst was characterized by infrared spectroscopy (FTIR), X-ray diffraction (XRD), Brunauer-Emmett-Teller method (BET), energy dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM). The efficiency of these [...] Read more.

Nanostructured β-CoMoO₄ catalysts have been prepared via the thermal decomposition of an oxalate precursor. The catalyst was characterized by infrared spectroscopy (FTIR), X-ray diffraction (XRD), Brunauer-Emmett-Teller method (BET), energy dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM). The efficiency of these nanoparticles in the reduction of ortho- and meta-nitrophenol isomers (2-NP, 3-NP, and 4-NP) to their corresponding aminophenols was tested using UV-visible spectroscopy measurements. It was found that, with a β-CoMoO₄ catalyst, NaBH₄ reduces 3-NP instantaneously, whilst the reduction of 2-NP and 4-NP is slower at 8 min. This difference is thought to arise from the lower acidity of 3-NP, where the negative charge of the phenolate could not be delocalized onto the oxygen atoms of the meta-nitro group. Full article

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11 pages, 2334 KiB

Open AccessArticle

Structure–Activity Relationship of Xanthones as Inhibitors of Xanthine Oxidase

by Ling-Yun Zhou^1,2, Jia-Le Peng³, Jun-Ming Wang¹, Yuan-Yuan Geng¹, Zhi-Li Zuo^3,* and Yan Hua^1,*

¹ Key Laboratory for Forest Resources Conservation and Use in the Southwest Mountains of China (Southwest Forestry University), Ministry of Education, Kunming 650224, China

² Anhui Provincial Engineering Research Center for Polysaccharide Drugs, School of Pharmacy, Wannan Medical College, Wuhu 241002, China

³ State Key Laboratory of Phytochemistry and Plant Resource in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China

Molecules 2018, 23(2), 365; https://doi.org/10.3390/molecules23020365 - 9 Feb 2018

Cited by 12 | Viewed by 4326

Abstract

Polygala plants contain a large number of xanthones with good physiological activities. In our previous work, 18 xanthones were isolated from Polygala crotalarioides. Extented study of the chemical composition of the other species Polygala sibirica led to the separation of two new xanthones—3-hydroxy-1,2,6,7,8-pentamethoxy [...] Read more.

Polygala plants contain a large number of xanthones with good physiological activities. In our previous work, 18 xanthones were isolated from Polygala crotalarioides. Extented study of the chemical composition of the other species Polygala sibirica led to the separation of two new xanthones—3-hydroxy-1,2,6,7,8-pentamethoxy xanthone (A) and 6-O-β-d-glucopyranosyl-1,7-dimethoxy xanthone (C)—together with 14 known xanthones. Among them, some xanthones have a certain xanthine oxidase (XO) inhibitory activity. Furthemore, 14 xanthones as XO inhibitors were selected to develop three-dimensional quantitative structure–activity relationship (3D-QSAR) using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models. The CoMFA model predicted a q² value of 0.613 and an r² value of 0.997. The best CoMSIA model predicted a q² value of 0.608 and an r² value of 0.997 based on a combination of steric, electrostatic, and hydrophobic effects. The analysis of the contour maps from each model provided insight into the structural requirements for the development of more active XO inhibitors. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 1256 KiB

Open AccessArticle

Inhibitory Effect of Sauchinone on UDP-Glucuronosyltransferase (UGT) 2B7 Activity

by Byoung Hoon You, Eun Chae Gong and Young Hee Choi^*

College of Pharmacy and Intergrated Research Institute for Drug Development, Dongguk University-Seoul, 32 Dongguk-lo, Ilsandong-gu, Goyang, Gyonggi-do 10326, Korea

Molecules 2018, 23(2), 366; https://doi.org/10.3390/molecules23020366 - 9 Feb 2018

Cited by 15 | Viewed by 4811

Abstract

Herb–drug interaction (HDI) limits clinical application of herbs and drugs, and inhibition of herbs towards uridine diphosphate (UDP)-glucuronosyltransferases (UGTs) has gained attention as one of the important reasons to cause HDIs. Sauchinone, an active lignan isolated from aerial parts of Saururus chinensis (Saururacease), [...] Read more.

Herb–drug interaction (HDI) limits clinical application of herbs and drugs, and inhibition of herbs towards uridine diphosphate (UDP)-glucuronosyltransferases (UGTs) has gained attention as one of the important reasons to cause HDIs. Sauchinone, an active lignan isolated from aerial parts of Saururus chinensis (Saururacease), possesses anti-oxidant, anti-inflammatory, and anti-viral activities. In pharmacokinetics of sauchinone, sauchinone is highly distributed to the liver, forming extensive metabolites of sauchinone via UGTs in the liver. Thus, we investigated whether sauchinone inhibited UGTs to explore potential of sauchinone–drug interactions. In human liver microsomes (HLMs), sauchinone inhibited activities of UGT1A1, 1A3, 1A6, and 2B7 with IC₅₀ values of 8.83, 43.9, 0.758, and 0.279 μM, respectively. Sauchinone also noncompetitively inhibited UGT1A6 and 2B7 with K_i values of 1.08 and 0.524 μM, respectively. In in vivo interaction study using mice, sauchinone inhibited UGT2B7-mediated zidovudine metabolism, resulting in increased systemic exposure of zidovudine when sauchinone and zidovudine were co-administered together. Our results indicated that there is potential HDI between sauchinone and drugs undergoing UGT2B7-mediated metabolism, possibly contributing to the safe use of sauchinone and drug combinations. Full article

(This article belongs to the Section Natural Products Chemistry)

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11 pages, 3162 KiB

Open AccessArticle

Effects of the Artificial Sweetener Neotame on the Gut Microbiome and Fecal Metabolites in Mice

by Liang Chi¹, Xiaoming Bian², Bei Gao², Pengcheng Tu¹, Yunjia Lai¹, Hongyu Ru³ and Kun Lu^1,*

¹ Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA

² Department of Environmental Health Science, University of Georgia, Athens, GA 30602, USA

³ Department of Population Health and Pathobiology, North Carolina State University, Raleigh, NC 27607, USA

Molecules 2018, 23(2), 367; https://doi.org/10.3390/molecules23020367 - 9 Feb 2018

Cited by 73 | Viewed by 55142

Abstract

Although artificial sweeteners are widely used in food industry, their effects on human health remain a controversy. It is known that the gut microbiota plays a key role in human metabolism and recent studies indicated that some artificial sweeteners such as saccharin could [...] Read more.

Although artificial sweeteners are widely used in food industry, their effects on human health remain a controversy. It is known that the gut microbiota plays a key role in human metabolism and recent studies indicated that some artificial sweeteners such as saccharin could perturb gut microbiome and further affect host health, such as inducing glucose intolerance. Neotame is a relatively new low-caloric and high-intensity artificial sweetener, approved by FDA in 2002. However, the specific effects of neotame on gut bacteria are still unknown. In this study, we combined high-throughput sequencing and gas chromatography–mass spectrometry (GC-MS) metabolomics to investigate the effects of neotame on the gut microbiome and fecal metabolite profiles of CD-1 mice. We found that a four-week neotame consumption reduced the alpha-diversity and altered the beta-diversity of the gut microbiome. Firmicutes was largely decreased while Bacteroidetes was significantly increased. The Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis also indicated that the control mice and neotame-treated mice have different metabolic patterns and some key genes such as butyrate synthetic genes were decreased. Moreover, neotame consumption also changed the fecal metabolite profiles. Dramatically, the concentrations of multiple fatty acids, lipids as well as cholesterol in the feces of neotame-treated mice were consistently higher than controls. Other metabolites, such as malic acid and glyceric acid, however, were largely decreased. In conclusion, our study first explored the specific effects of neotame on mouse gut microbiota and the results may improve our understanding of the interaction between gut microbiome and neotame and how this interaction could influence the normal metabolism of host bodies. Full article

(This article belongs to the Special Issue Sugar Substitutes and Obesity, Diabetes and Metabolic Syndrome)

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11 pages, 431 KiB

Open AccessArticle

Dietary Phytoestrogen Intake is Inversely Associated with Hypertension in a Cohort of Adults Living in the Mediterranean Area

by Justyna Godos^1,2,*

, Sonia Bergante³, Angela Satriano³, Francesca Romana Pluchinotta³ and Marina Marranzano¹

¹ Department of Medical and Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95125 Catania, Italy

² Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy

³ IRCCS Policlinico San Donato, 20097 San Donato Milanese (MI), Italy

Molecules 2018, 23(2), 368; https://doi.org/10.3390/molecules23020368 - 9 Feb 2018

Cited by 27 | Viewed by 5443

Abstract

Background: Dietary polyphenols, including phytoestrogens are abundantly present in a balanced diet. Evidence for their role in preventing non-communicable diseases is emerging. Methods: We examined the association between estimated habitual intakes of dietary phytoestrogens and hypertension in a cohort study. The baseline data [...] Read more.

Background: Dietary polyphenols, including phytoestrogens are abundantly present in a balanced diet. Evidence for their role in preventing non-communicable diseases is emerging. Methods: We examined the association between estimated habitual intakes of dietary phytoestrogens and hypertension in a cohort study. The baseline data included 1936 men and women aged 18 years and older. Intakes of total phytoestrogens, isoflavones, and lignans were calculated from validated food frequency questionnaire. Data on the polyphenols content in foods were retrieved from the Phenol-Explorer database. Results: Individuals in the highest quartile of dietary phytoestrogens intake were less likely to be hypertensive (OR: 0.66, 95% CI: 0.44–0.98); moreover, the association showed a significant decreasing trend. Isoflavones and lignans were not associated with lower odds of hypertension; however, some individual compounds, such as biochanin A and pinoresinol showed an independent inverse association with hypertension. Conclusions: Dietary phytoestrogens are associated with lower likelihood of hypertension in adults living in the Mediterranean area. Future studies are needed to confirm the present findings (i.e., prospective cohort studies) and to better understand the mechanisms underlying such associations. Full article

(This article belongs to the Special Issue Dietary Antioxidants: Evidence of Protective Effects against Chronic Disease)

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10 pages, 714 KiB

Open AccessArticle

Aethiopinolones A–E, New Pregnenolone Type Steroids from the East African Basidiomycete Fomitiporia aethiopica

by Clara Chepkirui^1,†, Winnie C. Sum^2,†, Tian Cheng¹, Josphat C. Matasyoh³, Cony Decock⁴ and Marc Stadler^1,*

¹ Department of Microbial Drugs, Helmholtz Centre for Infection Research and German Centre for Infection Research (DZIF), Partner Site Hannover/Braunschweig, Inhoffenstrasse 7, 38124 Braunschweig, Germany

² Department of Biochemistry, Egerton University, P.O. BOX 536, Njoro 20115, Kenya

³ Department of Chemistry, Egerton University, P.O. BOX 536, Njoro 20115, Kenya

⁴ Mycothéque de l’ Universite Catholique de Louvain (BCCM/MUCL), Place Croix du Sud 3, B-1348 Louvain-la-Neuve, Belgium

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 369; https://doi.org/10.3390/molecules23020369 - 9 Feb 2018

Cited by 15 | Viewed by 3696

Abstract

A mycelial culture of the Kenyan basidiomycete Fomitiporia aethiopica was fermented on rice and the cultures were extracted with methanol. Subsequent HPLC profiling and preparative chromatography of its crude extract led to the isolation of five previously undescribed pregnenolone type triterpenes 1– [...] Read more.

A mycelial culture of the Kenyan basidiomycete Fomitiporia aethiopica was fermented on rice and the cultures were extracted with methanol. Subsequent HPLC profiling and preparative chromatography of its crude extract led to the isolation of five previously undescribed pregnenolone type triterpenes 1–5, for which we propose the trivial name aethiopinolones A–E. The chemical structures of the aethiopinolones were determined by extensive 1D- and 2D-NMR, and HRMS data analysis. The compounds exhibited moderate cytotoxic effects against various human cancer cell lines, but they were found devoid of significant nematicidal and antimicrobial activities. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 3744 KiB

Open AccessArticle

Contribution of Polyphenol Oxidation, Chlorophyll and Vitamin C Degradation to the Blackening of Piper nigrum L.

by Fenglin Gu^1,2,3, Feifei Huang¹, Guiping Wu^1,2,3 and Hongying Zhu^1,2,3,*

¹ Spice and Beverage Research Institute, Chinese Academy of Tropical Agricultural Sciences (CATAS), Wanning 571533, China

² National Center of Important Tropical Crops Engineering and Technology Research, Wanning 571533, China

³ Key Laboratory of Genetic Resources Utilization of Spice and Beverage Crops, Ministry of Agriculture, Wanning 571533, China

Molecules 2018, 23(2), 370; https://doi.org/10.3390/molecules23020370 - 9 Feb 2018

Cited by 24 | Viewed by 4503

Abstract

Black pepper (Piper nigrum L.) is the most widely used spice in the world. Blackening is considered to be beneficial and important in the processing of black pepper because it contributes to its color and flavor. The purpose of this paper is [...] Read more.

Black pepper (Piper nigrum L.) is the most widely used spice in the world. Blackening is considered to be beneficial and important in the processing of black pepper because it contributes to its color and flavor. The purpose of this paper is to investigate polyphenol oxidation as well as the chlorophyll and vitamin C (VC) degradation in the blackening of Piper nigrum L. Black pepper was produced by four methods, and changes in polyphenols, chlorophyll and VC were studied by high performance liquid chromatography (HPLC) and ultraviolet-visible and visible (UV-Vis) spectrophotometry. The results show that polyphenol oxidase activity significantly decreased during the preparation of black pepper, and the concentrations of phenolic compounds, VC, and chlorophyll a and b also significantly decreased. Polyphenol oxidation and chlorophyll and VC degradation contribute to the blackening. A crude extract of phenolic compounds from black pepper was prepared by the system solvent method. The greater the polarity of the extraction solvent, the higher the extraction rates of the phenolic compounds and the total phenol content. Pepper phenolic compounds were analyzed by HPLC analysis. Full article

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10 pages, 3745 KiB

Open AccessArticle

Synthesis and Magnetic Properties of Stable Radical Derivatives Carrying a Phenylacetylene Unit

by Shogo Miyashiro, Tomoaki Ishii, Youhei Miura and Naoki Yoshioka^*

Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama 223-8522, Japan

Molecules 2018, 23(2), 371; https://doi.org/10.3390/molecules23020371 - 9 Feb 2018

Cited by 5 | Viewed by 3937

Abstract

A nitronyl nitroxide derivative, 2-phenylethynyl-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-1-oxyl-3-oxide (1), and two verdazyl derivatives carrying a phenylacetylene unit, 1,5-diphenyl-3-phenylethynyl-6-oxo-1,2,4,5-tetrazin-2-yl (2) and 1,5-diisopropyl-3-phenylethynyl-6-oxo-1,2,4,5-tetrazin-2-yl (3), were synthesized and their packing structures were studied by X-ray crystallographic analysis and magnetically characterized in [...] Read more.

A nitronyl nitroxide derivative, 2-phenylethynyl-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-1-oxyl-3-oxide (1), and two verdazyl derivatives carrying a phenylacetylene unit, 1,5-diphenyl-3-phenylethynyl-6-oxo-1,2,4,5-tetrazin-2-yl (2) and 1,5-diisopropyl-3-phenylethynyl-6-oxo-1,2,4,5-tetrazin-2-yl (3), were synthesized and their packing structures were studied by X-ray crystallographic analysis and magnetically characterized in the solid state. While 1 and 3 had an isolated doublet spin state, 2 formed an antiferromagnetically coupled pair (2J/k_B = −118 K). Density functional theory (DFT) calculations reveal that the spin density polarized in the phenyl group decreases as the dihedral angle between the phenyl ring and radical plane increases. Full article

(This article belongs to the Section Physical Chemistry)

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16 pages, 2283 KiB

Open AccessArticle

Nectandra grandiflora By-Products Obtained by Alternative Extraction Methods as a Source of Phytochemicals with Antioxidant and Antifungal Properties

by Daniela Thomas Da Silva¹, Rene Herrera²

, Berta Maria Heinzmann³, Javier Calvo⁴ and Jalel Labidi^2,*

¹ Center of Rural Sciences, Federal University of Santa Maria, Ave. Roraima 1000, Santa Maria 97105-900, Brazil

² Biorefinery Processes Research Group, Department of Chemical and Environmental Engineering, University of the Basque Country (UPV/EHU), Plaza Europa 1, 20018 Donostia, Spain

³ Department of Industrial Pharmacy, Federal University of Santa Maria, Ave. Roraima 1000, Santa Maria 97105-900, Brazil

⁴ Chromatography and Mass Spectrometry Platform, CIC BiomaGUNE, Paseo Miramon 182, 200009 San Sebastian, Spain

Molecules 2018, 23(2), 372; https://doi.org/10.3390/molecules23020372 - 9 Feb 2018

Cited by 10 | Viewed by 3798

Abstract

Nectandra grandiflora Nees (Lauraceae) is a Brazilian native tree recognized by its durable wood and the antioxidant compounds of its leaves. Taking into account that the forest industry offers the opportunity to recover active compounds from its residues and by-products, this study identifies [...] Read more.

Nectandra grandiflora Nees (Lauraceae) is a Brazilian native tree recognized by its durable wood and the antioxidant compounds of its leaves. Taking into account that the forest industry offers the opportunity to recover active compounds from its residues and by-products, this study identifies and underlines the potential of natural products from Nectandra grandiflora that can add value to the forest exploitation. This study shows the effect of three different extraction methods: conventional (CE), ultrasound-assisted (UAE) and microwave-assisted (MAE) on Nectandra grandiflora leaf extracts (NGLE) chemical yields, phenolic and flavonoid composition, physical characteristics as well as antioxidant and antifungal properties. Results indicate that CE achieves the highest extraction phytochemical yield (22.16%), but with similar chemical composition to that obtained by UAE and MAE. Moreover, CE also provided a superior thermal stability of NGLE. The phenolic composition of NGLE was confirmed firstly, by colorimetric assays and infrared spectra and then by chromatographic analysis, in which quercetin-3-O-rhamnoside was detected as the major compound (57.75–65.14%). Furthermore, the antioxidant capacity of the NGLE was not altered by the extraction methods, finding a high radical inhibition in all NGLE (>80% at 2 mg/mL). Regarding the antifungal activity, there was observed that NGLE possess effective bioactive compounds, which inhibit the Aspergillus niger growth. Full article

(This article belongs to the Special Issue Extractable and Non-Extractable Antioxidants)

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17 pages, 1784 KiB

Open AccessArticle

Segmenting Proteins into Tripeptides to Enhance Conformational Sampling with Monte Carlo Methods

by Laurent Denarie, Ibrahim Al-Bluwi^†, Marc Vaisset, Thierry Siméon and Juan Cortés^*

¹ LAAS-CNRS, Université de Toulouse, CNRS, 31400 Toulouse, France

^† Current address: Computer Science Department, Princeton University, Princeton, NJ 08540, USA.

Molecules 2018, 23(2), 373; https://doi.org/10.3390/molecules23020373 - 9 Feb 2018

Cited by 9 | Viewed by 3372

Abstract

This paper presents an approach to enhance conformational sampling of proteins employing stochastic algorithms such as Monte Carlo (MC) methods. The approach is based on a mechanistic representation of proteins and on the application of methods originating from robotics. We outline the general [...] Read more.

This paper presents an approach to enhance conformational sampling of proteins employing stochastic algorithms such as Monte Carlo (MC) methods. The approach is based on a mechanistic representation of proteins and on the application of methods originating from robotics. We outline the general ideas of our approach and detail how it can be applied to construct several MC move classes, all operating on a shared representation of the molecule and using a single mathematical solver. We showcase these sampling techniques on several types of proteins. Results show that combining several move classes, which can be easily implemented thanks to the proposed approach, significantly improves sampling efficiency. Full article

(This article belongs to the Special Issue Selected Papers from the 10th Computational Structural Bioinformatics Workshop (CSBW-2017))

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10 pages, 2614 KiB

Open AccessArticle

Inhibitory Effect of Flavonolignans on the P2Y12 Pathway in Blood Platelets

by Michal Bijak^*

, Rafal Szelenberger, Angela Dziedzic and Joanna Saluk-Bijak

Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland

Molecules 2018, 23(2), 374; https://doi.org/10.3390/molecules23020374 - 10 Feb 2018

Cited by 15 | Viewed by 4779

Abstract

Adenosine diphosphate (ADP) is the major platelet agonist, which is important in the shape changes, stability, and growth of the thrombus. Platelet activation by ADP is associated with the G protein-coupled receptors P2Y1 and P2Y12. The pharmacologic blockade of the P2Y12 receptor significantly [...] Read more.

Adenosine diphosphate (ADP) is the major platelet agonist, which is important in the shape changes, stability, and growth of the thrombus. Platelet activation by ADP is associated with the G protein-coupled receptors P2Y1 and P2Y12. The pharmacologic blockade of the P2Y12 receptor significantly reduces the risk of peripheral artery disease, myocardial infarction, ischemic stroke, and vascular death. Recent studies demonstrated the inhibition of ADP-induced blood platelet activation by three major compounds of the flavonolignans group: silybin, silychristin, and silydianin. For this reason, the aim of the current work was to verify the effects of silybin, silychristin, and silydianin on ADP-induced physiological platelets responses, as well as mechanisms of P2Y12-dependent intracellular signal transduction. We evaluated the effect of tested flavonolignans on ADP-induced blood platelets’ aggregation in platelet-rich plasma (PRP) (using light transmission aggregometry), adhesion to fibrinogen (using the static method), and the secretion of PF-4 (using the ELISA method). Additionally, using the double labeled flow cytometry method, we estimated platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation. We demonstrated a dose-dependent reduction of blood platelets’ ability to perform ADP-induced aggregation, adhere to fibrinogen, and secrete PF-4 in samples treated with flavonolignans. Additionally, we observed that all of the tested flavonolignans were able to increase VASP phosphorylation in blood platelets samples, which is correlated with P2Y12 receptor inhibition. All of these analyses show that silychristin and silybin have the strongest inhibitory effect on blood platelet activation by ADP, while silydianin also inhibits the ADP pathway, but to a lesser extent. The results obtained in this study clearly demonstrate that silybin, silychristin, and silydianin have inhibitory properties against the P2Y12 receptor and block ADP-induced blood platelet activation. Full article

(This article belongs to the Collection Bioactive Compounds)

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13 pages, 3480 KiB

Open AccessArticle

Functional Magnetic Mesoporous Silica Microparticles Capped with an Azo-Derivative: A Promising Colon Drug Delivery Device

by Adrián H. Teruel^1,2

, Carmen Coll^1,2, Ana M. Costero^1,2,3

, Daniel Ferri^1,3, Margarita Parra^1,2,3, Pablo Gaviña^1,2,3, Marta González-Álvarez⁴, Virginia Merino^1,5

, M. Dolores Marcos^1,2,6,7, Ramón Martínez-Máñez^1,2,6,7,*

and Félix Sancenón^1,2,6,7

¹ Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM), Polytechnic University of Valencia, University of Valencia, 46100 Valencia, Spain

² CIBER of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain

³ Department of Organic Chemistry, University of Valencia, 46100 Valencia, Spain

⁴ Engineering Department. Pharmacy and Pharmaceutical Technology Section, Miguel Hernandez University, 03550 Alicante, Spain

⁵ Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, Spain

⁶ Joint Research Unit in Nanomedicine and Sensors. Polytechnic University of Valencia, Health Research Institute Hospital La Fe, 46100 Valencia, Spain.

⁷ Joint Unit CIPF-UPV of Mechanisms of Diseases and Nanomedicine, Valencia, Polytechnic University of Valencia, Prince Felipe Research Center, 46100 Valencia, Spain

Molecules 2018, 23(2), 375; https://doi.org/10.3390/molecules23020375 - 10 Feb 2018

Cited by 13 | Viewed by 5033

Abstract

Magnetic micro-sized mesoporous silica particles were used for the preparation of a gated material able to release an entrapped cargo in the presence of an azo-reducing agent and, to some extent, at acidic pH. The magnetic mesoporous microparticles were loaded with safranin O [...] Read more.

Magnetic micro-sized mesoporous silica particles were used for the preparation of a gated material able to release an entrapped cargo in the presence of an azo-reducing agent and, to some extent, at acidic pH. The magnetic mesoporous microparticles were loaded with safranin O and the external surface was functionalized with an azo derivative 1 (bearing a carbamate linkage) yielding solid S1. Aqueous suspensions of S1 at pH 7.4 showed negligible safranin O release due to the presence of the bulky azo derivative attached onto the external surface of the inorganic scaffold. However, in the presence of sodium dithionite (azoreductive agent), a remarkable safranin O delivery was observed. At acidic pH, a certain safranin O release from S1 was also found. The pH-triggered safranin O delivery was ascribed to the acid-induced hydrolysis of the carbamate moiety that linked the bulky azo derivatives onto the mesoporous inorganic magnetic support. The controlled release behavior of S1 was also tested using a model that simulated the gastro intestinal tract. Full article

(This article belongs to the Special Issue Coordination Chemistry for Devices and Functional Materials)

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14 pages, 4107 KiB

Open AccessArticle

Synthesis and Fluorescent Property Study of Novel 1,8-Naphthalimide-Based Chemosensors

by Ying Fu¹

, Xiao-Xiao Pang¹, Zhi-Qiang Wang¹, Hai-Tao Qu² and Fei Ye^1,*

¹ Department of Applied Chemistry, College of Science, Northeast Agricultural University, Harbin 150030, China

² Quality supervision and Inspection Institute, Harbin 150030, China

Molecules 2018, 23(2), 376; https://doi.org/10.3390/molecules23020376 - 10 Feb 2018

Cited by 19 | Viewed by 6489

Abstract

A series of novel mono- and di-substituted N-n-butyl-1,8-naphthalimide derivatives were synthesized simultaneously via a three-step reaction. The single crystal structure of N-n-butyl-4-[N′,N′-bis(2′,4′-dichlorobenzoyl)ethylamino]-1,8-naphthalimide (3f) was determined. The UV-vis and fluorescence properties of compound 3f were investigated. [...] Read more.

A series of novel mono- and di-substituted N-n-butyl-1,8-naphthalimide derivatives were synthesized simultaneously via a three-step reaction. The single crystal structure of N-n-butyl-4-[N′,N′-bis(2′,4′-dichlorobenzoyl)ethylamino]-1,8-naphthalimide (3f) was determined. The UV-vis and fluorescence properties of compound 3f were investigated. The 3f showed highly selective and sensitive fluorescence changes response towards Pb²⁺. A titration of monomer with Pb²⁺ ion was performed. When Pb²⁺ ion concentration increased from 0 to 10 eq., the fluorescent intensity of 3f decreased from 199.97 to 48.21. The pH effect on 3f showed that it is stable in a wide range of pH. The results indicated that 3f might be a probe molecule for Pb²⁺. Full article

(This article belongs to the Section Organic Chemistry)

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21 pages, 4349 KiB

Open AccessFeature PaperArticle

Quantification and Variability Analysis of Lignin Optical Properties for Colour-Dependent Industrial Applications

by Olumoye Ajao¹

, Jawad Jeaidi¹, Marzouk Benali^1,*, Andrea M. Restrepo², Naima El Mehdi² and Yacine Boumghar²

¹ Natural Resources Canada, CanmetENERGY, Varennes, QC J3X 1P7, Canada

² Centre d’études des procédés chimiques du Québec (CEPROCQ), Montreal, QC H1N 1C1, Canada

Molecules 2018, 23(2), 377; https://doi.org/10.3390/molecules23020377 - 10 Feb 2018

Cited by 56 | Viewed by 7011

Abstract

Lignin availability has increased significantly due to the commercialization of several processes for recovery and further development of alternatives for integration into Kraft pulp mills. Also, progress in lignin characterization, understanding of its chemistry as well as processing methods have resulted in the [...] Read more.

Lignin availability has increased significantly due to the commercialization of several processes for recovery and further development of alternatives for integration into Kraft pulp mills. Also, progress in lignin characterization, understanding of its chemistry as well as processing methods have resulted in the identification of novel lignin-based products and potential derivatives, which can serve as building block chemicals. However, all these have not led to the successful commercialization of lignin-based chemicals and materials. This is because most analyses and characterizations focus only on the technical suitability and quantify only the composition, functional groups present, size and morphology. Optical properties, such as the colour, which influences the uptake by users for diverse applications, are neither taken into consideration nor analysed. This paper investigates the quantification of lignin optical properties and how they can be influenced by process operating conditions. Lignin extraction conditions were also successfully correlated to the powder colour. About 120 lignin samples were collected and the variability of their colours quantified with the CIE L*a*b* colour space. In addition, a robust and reproducible colour measurement method was developed. This work lays the foundation for identifying chromophore molecules in lignin, as a step towards correlating the colour to the functional groups and the purity. Full article

(This article belongs to the Special Issue Lignin for Energy, Chemicals and Materials)

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16 pages, 908 KiB

Open AccessArticle

Bioactive Compounds in Cornelian Cherry Vinegars

by Joanna Kawa-Rygielska^1,*, Kinga Adamenko¹, Alicja Z. Kucharska²

and Narcyz Piórecki^3,4

¹ Department of Fermentation and Cereals Technology, Faculty of Food Science, 51-630 Wrocław, Poland

² Department of Fruit, Vegetable and Plant Nutraceutical Technology, Faculty of Food Science, Wroclaw University of Environmental and Life Sciences, 51-630 Wroław, Poland

³ Arboretum and Institute of Physiography in Bolestraszyce, 37-700 Przemyśl, Poland

⁴ Faculty of Physical Educaion, University of Rzeszów, 35-959 Rzeszów, Poland

Molecules 2018, 23(2), 379; https://doi.org/10.3390/molecules23020379 - 10 Feb 2018

Cited by 40 | Viewed by 5846

Abstract

We analyzed the effect of Cornelian cherry varieties differing in fruit color (‘Yantaryi’—yellow fruits, ‘Koralovyi’—coral fruits, ‘Podolski’—red fruits) and the production method on the physicochemical and antioxidative properties of Cornelian cherry vinegars, and on their content of iridoids and polyphenols. Acetic fermentation was [...] Read more.

We analyzed the effect of Cornelian cherry varieties differing in fruit color (‘Yantaryi’—yellow fruits, ‘Koralovyi’—coral fruits, ‘Podolski’—red fruits) and the production method on the physicochemical and antioxidative properties of Cornelian cherry vinegars, and on their content of iridoids and polyphenols. Acetic fermentation was conducted by two methods: I) single-stage (spontaneous) acetic fermentation, without inoculation with microorganisms, and II) two-stage fermentation in which the first stage involved the use of Saccharomyces bayanus—Safspirit fruit yeast for alcoholic fermentation, and the second one included spontaneous acetic fermentation. Acetic acid, glycerol, individual iridoids, phenolic acids, flavonols, and anthocyanins were quantified by a high-performance liquid chromatography (HPLC) method. The antioxidative activity was determined based on the following tests: 2,2-Diphenyl-2-picryl-hydrazyl (DPPH^•), 2,2′-Azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid (ABTS^•+), and ferric reducing antioxidant power (FRAP), while the total polyphenols content was determined using the Folin-Ciocialteu (F-C) reagent test. Both the Cornelian cherry variety and vinegar production method affected the antioxidative properties as well as concentrations of iridoids and polyphenols in the finished product. The concentration of total polyphenols (F-C) in vinegars ranged from 326.60 to 757.27 mg gallic acids equivalents (GAE)/100 mL vinegar, whereas the antioxidative activity assayed with the DPPH^• and FRAP methods was the highest in the vinegars produced from the coral and red varieties of Cornelian cherry with the two-stage method. Loganic acid predominated among the identified iridoids, reaching a concentration of 185.07 mg loganic acid (LA)/100 mL in the vinegar produced in the two-stage fermentation from the coral-fruit variety. Caffeoylquinic acid derivatives were the main representatives among the identified phenolic compounds. The results of this study demonstrate Cornelian cherry vinegars to be rich sources of biologically-active iridoids and phenolic compounds with antioxidative properties. Full article

(This article belongs to the Collection Bioactive Compounds)

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14 pages, 3945 KiB

Open AccessArticle

The Effect of Ginger Juice Processing on the Chemical Profiles of Rhizoma coptidis

by Chunyu Yang¹

, Fengqian Guo¹, Chen Zang¹, Cui Li¹, Hui Cao² and Baoxian Zhang^1,*

¹ Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China

² School of Pharmacy, Jinan University, Guangzhou 510632, China

Molecules 2018, 23(2), 380; https://doi.org/10.3390/molecules23020380 - 10 Feb 2018

Cited by 11 | Viewed by 4539

Abstract

Rhizoma coptidis (RC) has been used as an herbal medicine in China for over one thousand years, and it was subjected to specific processing before use as materia medica. Processing is a pharmaceutical technique that aims to enhance the efficacy and/or reduce the [...] Read more.

Rhizoma coptidis (RC) has been used as an herbal medicine in China for over one thousand years, and it was subjected to specific processing before use as materia medica. Processing is a pharmaceutical technique that aims to enhance the efficacy and/or reduce the toxicity of crude drugs according to traditional Chinese medicine theory. In this study, the chemical profiles of RC, ginger juice processed RC (GRC), and water processed RC (WRC) was determined to reveal the mechanism of processing of RC. UPLC-QTOF-MS analysis of methanol extract of RC, GRC, and WRC has been conducted to investigate the effect of processing on the composition of RC. HPLC-PDA was used to determine the variance of total alkaloids and seven alkaloids of RC during the processing. The volatiles of RC, GRC and ginger juice were separated by distillation, the change of volatiles content was recorded and analyzed, and the qualitative analysis of the volatiles was carried out using GC-MS. The microstructures of RC, GRC and WRC were observed using a light microscope. Results showed that ginger juice/water processing had limited influence on the composition of RC’s methanol extract, but significant influence on the content of some alkaloids in RC. Ginger juice processing significantly increased (p < 0.05) the volatiles content of RC and changed the volatiles composition obviously. Processing also had an influence on the microstructure of RC. This research comprehensively revealed the mechanism of ginger juice processing of RC. Full article

(This article belongs to the Collection Herbal Medicine Research)

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9 pages, 1866 KiB

Open AccessArticle

Separation and Purification of Fructo-Oligosaccharide by High-Speed Counter-Current Chromatography Coupled with Precolumn Derivatization

by Wenjuan Duan¹, Wenhua Ji¹, Yuanan Wei², Ruixuan Zhao¹, Zijian Chen², Yanling Geng¹, Feng Jing¹ and Xiao Wang^1,*

¹ Qilu University of Technology (Shandong Academy of Sciences), Shandong Analysis and Test Center, Shandong Key Laboratory of TCM Quality Control Technology, 19 Keyuan Street, Jinan 250014, Shandong, China

² Quantum Hi-Tech (China) Biological Co., Ltd., 133 Gaoxin Road West, Hi-tech Zone, Jiangmen 529081, Guangdong, China

Molecules 2018, 23(2), 381; https://doi.org/10.3390/molecules23020381 - 10 Feb 2018

Cited by 13 | Viewed by 3469

Abstract

High-speed counter-current chromatography (HSCCC) coupled with precolumn derivatization was developed for isolating and purifying fructo-oligosaccharides (FOSs). Firstly, the total FOSs were precolumn derivatized and then separated by high-speed counter-current chromatography (HSCCC) with two-phase solvent system petroleum ether–n-butanol–methanol–water (3:2:1:4, v/v [...] Read more.

High-speed counter-current chromatography (HSCCC) coupled with precolumn derivatization was developed for isolating and purifying fructo-oligosaccharides (FOSs). Firstly, the total FOSs were precolumn derivatized and then separated by high-speed counter-current chromatography (HSCCC) with two-phase solvent system petroleum ether–n-butanol–methanol–water (3:2:1:4, v/v). Secondly, the obtained compounds were deacetylated and the fructo-oligosaccharides (FOSs) with high purity were obtained. Their structures were identified by mass spectrometry (MS) and nuclear magnetic resonance (NMR). This research successfully established a novel strategy for separation and purification of FOS. There is no doubt that the application of the research will be beneficial for the quantitative and qualitative analysis of products containing FOSs. Full article

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16 pages, 3639 KiB

Open AccessArticle

Complex Formation of Resorufin and Resazurin with Β-Cyclodextrins: Can Cyclodextrins Interfere with a Resazurin Cell Viability Assay?

by Rita Csepregi^1,2, Beáta Lemli^2,3,4

, Sándor Kunsági-Máté^2,3,4, Lajos Szente⁵, Tamás Kőszegi^1,2

, Balázs Németi⁶ and Miklós Poór^2,6,*

¹ Department of Laboratory Medicine, University of Pécs, Medical School, Pécs H-7624, Hungary

² János Szentágothai Research Center, University of Pécs, Pécs H-7624, Hungary

³ Department of General and Physical Chemistry, University of Pécs, Pécs H-7624, Hungary

⁴ Department of Pharmaceutical Chemistry, University of Pécs, Faculty of Pharmacy, Pécs H-7624, Hungary

⁵ CycloLab Cyclodextrin Research & Development Laboratory, Ltd., Budapest H-1097, Hungary

⁶ Department of Pharmacology, University of Pécs, Faculty of Pharmacy, Pécs H-7624, Hungary

Molecules 2018, 23(2), 382; https://doi.org/10.3390/molecules23020382 - 10 Feb 2018

Cited by 28 | Viewed by 13269

Abstract

Resazurin (or Alamar Blue) is a poorly fluorescent dye. During the cellular reduction of resazurin, its highly fluorescent product resorufin is formed. Resazurin assay is a commonly applied method to investigate viability of bacterial and mammalian cells. In this study, the interaction of [...] Read more.

Resazurin (or Alamar Blue) is a poorly fluorescent dye. During the cellular reduction of resazurin, its highly fluorescent product resorufin is formed. Resazurin assay is a commonly applied method to investigate viability of bacterial and mammalian cells. In this study, the interaction of resazurin and resorufin with β-cyclodextrins was investigated employing spectroscopic and molecular modeling studies. Furthermore, the influence of β-cyclodextrins on resazurin-based cell viability assay was also tested. Both resazurin and resorufin form stable complexes with the examined β-cyclodextrins (2.0–3.1 × 10³ and 1.3–1.8 × 10³ L/mol were determined as binding constants, respectively). Cells were incubated for 30 and 120 min and treated with resazurin and/or β-cyclodextrins. Our results suggest that cyclodextrins are able to interfere with the resazurin-based cell viability assay that presumably results from the following mechanisms: (1) inhibition of the cellular uptake of resazurin and (2) enhancement of the fluorescence signal of the formed resorufin. Full article

(This article belongs to the Section Chemical Biology)

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7 pages, 711 KiB

Open AccessArticle

Two New Triterpenoids from the Roots of Codonopsis pilosula

by Tao Zheng^1,2, Li-Zhi Cheng³, Yong-Ming Yan³, Bao-Hua Liu³, Fu-Ying Qin^1,3

, Fu-Rong Xu^2,* and Yong-Xian Cheng^1,2,3,4,*

¹ College of Pharmacy, Yunnan University of Traditional Chinese Medicine, Kunming 650504, China

² State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China

³ Guangdong Key Laboratory for Genome Stability & Disease Prevention, School of Pharmaceutical Sciences, Shenzhen University Health Sciences Center, Shenzhen 518060, China

⁴ College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450008, China

Molecules 2018, 23(2), 383; https://doi.org/10.3390/molecules23020383 - 11 Feb 2018

Cited by 15 | Viewed by 3636

Abstract

Pseudolarolides U and V, two new triterpenoids, and four biogenetically related compounds, pseudolarolides E, F, K, and P were isolated from the roots of Codonopsis pilosula (Campanulaceae). Their structures were determined by spectroscopic data. The regulation of Sirtuin 1 (SIRT1) activity by all [...] Read more.

Pseudolarolides U and V, two new triterpenoids, and four biogenetically related compounds, pseudolarolides E, F, K, and P were isolated from the roots of Codonopsis pilosula (Campanulaceae). Their structures were determined by spectroscopic data. The regulation of Sirtuin 1 (SIRT1) activity by all the isolated compounds was evaluated. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 1439 KiB

Open AccessCommunication

Wogonin Suppresses the Activity of Matrix Metalloproteinase-9 and Inhibits Migration and Invasion in Human Hepatocellular Carcinoma

by Ming Hong^1,*,†, Honghui Cheng^2,†, Lei Song¹, Wencai Wang¹, Qi Wang¹, Donggang Xu³ and Weiwei Xing^3,*

¹ Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 12 Jichang Road, Guangzhou 510405, China

² College of mechanical engineering, Yangzhou University, 88 South University Ave., Yangzhou 225009, China

³ Department of Genome Engineering, Beijing Institute of Basic Medical Sciences, Taiping Road 27, Beijing 100850, China

^† These authors contribute equally to this work.

Molecules 2018, 23(2), 384; https://doi.org/10.3390/molecules23020384 - 11 Feb 2018

Cited by 34 | Viewed by 5061

Abstract

As one of the major active ingredients in Radix Scutellariae, wogonin has been shown to be associated with various pharmacological activities on cancer cell growth, apoptosis, and cell invasion and migration. Here, we demonstrated that wogonin may harbor potential anti-metastatic activities in hepatocarcinoma [...] Read more.

As one of the major active ingredients in Radix Scutellariae, wogonin has been shown to be associated with various pharmacological activities on cancer cell growth, apoptosis, and cell invasion and migration. Here, we demonstrated that wogonin may harbor potential anti-metastatic activities in hepatocarcinoma (HCC). The anti-metastasis potential of wogonin and its underlying mechanisms were evaluated by ligand–protein docking approach, surface plasmon resonance assay, and in vitro gelatin zymography studies. Our results showed that wogonin (100 μM, 50 μM) suppressed MHCC97L and PLC/PRF/5 cells migration and invasion in vitro. The docking approach and surface plasmon resonance assay indicated that the potential binding affinity between wogonin and matrix metalloproteinase-9 (MMP-9) may lead to inhibition of MMP-9 activity and further leads to suppression of tumor metastasis. This conclusion was further verified by Western blot results and gelatin zymography analysis. Wogonin might be a potent treatment option for disrupting the tumor metastasis that favors HCC development. The potential active targets from computational screening integrated with biomedical study may help us to explore the molecular mechanism of herbal medicines. Full article

(This article belongs to the Collection Natural Products: Anticancer Potential and Beyond)

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15 pages, 2147 KiB

Open AccessArticle

Physicochemical Properties and Oxidative Storage Stability of Milled Roselle (Hibiscus sabdariffa L.) Seeds

by Nurul Hanisah Juhari^1,2,*

and Mikael Agerlin Petersen¹

¹ Department of Food Science, Faculty of Science, University of Copenhagen, Rolighedsvej 26, Frederiksberg C, DK-1958, 1165 København, Denmark

² Department of Food Service and Management, Faculty of Food Science and Technology, University Putra Malaysia, Serdang 43400, Selangor, Malaysia

Molecules 2018, 23(2), 385; https://doi.org/10.3390/molecules23020385 - 11 Feb 2018

Cited by 11 | Viewed by 4514

Abstract

Milled Roselle (Hibiscus sabdariffa L.) seeds of the UMKL cultivar were analyzed for proximate composition, water and oil absorption capacity, and the influence of storage conditions on storage stability. The storage stability was determined under four types of conditions: light/oxygen (air) (LO), [...] Read more.

Milled Roselle (Hibiscus sabdariffa L.) seeds of the UMKL cultivar were analyzed for proximate composition, water and oil absorption capacity, and the influence of storage conditions on storage stability. The storage stability was determined under four types of conditions: light/oxygen (air) (LO), light/nitrogen (LN), darkness/oxygen (air) (DO), and darkness/nitrogen (DN) while monitoring for seven consecutive months. During the storage period, the formation of volatiles was determined using dynamic headspace sampling and Gas Chromatography-Mass Spectrometry (GC-MS) analysis. In total, 85 volatiles were identified, mainly aldehydes, alcohols, ketones, furans, and acids indicating lipid oxidation. It is recommended that milled Roselle seeds should be flushed with nitrogen and stored in darkness. Under these conditions, the seeds can be stored for at least three months without changes in volatile profile. This is important to ensure the good quality of milled Roselle seeds for further commercialization. Full article

(This article belongs to the Section Natural Products Chemistry)

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0 pages, 3036 KiB

Open AccessArticle

Melatonin Alleviates High Temperature-Induced Pollen Abortion in Solanum lycopersicum

by Zhen-Yu Qi^1,2,†, Kai-Xin Wang^1,†, Meng-Yu Yan¹, Mukesh Kumar Kanwar¹, Dao-Yi Li³, Leonard Wijaya⁴, Mohammed Nasser Alyemeni⁴, Parvaiz Ahmad⁴ and Jie Zhou^1,*

¹ Department of Horticulture/Zhejiang Provincial Key Laboratory of Horticultural Plant Integrative Biology, Zhejiang University, Hangzhou 310058, China

² Agricultural Experiment Station, Zhejiang University, Hangzhou 310058, China

³ Chinese Academy of Agricultural Mechanization Sciences, Beijing 10083, China

⁴ Department of Botany and Microbiology, Faculty of Science, King Saud University, Riyadh 11451, Saudi Arabia

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 386; https://doi.org/10.3390/molecules23020386 - 11 Feb 2018

Cited by 89 | Viewed by 6607 | Correction

Abstract

Melatonin is a pleiotropic signal molecule that plays critical roles in regulating plant growth and development, as well as providing physiological protections against various environmental stresses. Nonetheless, the mechanisms for melatonin-mediated pollen thermotolerance remain largely unknown. In this study, we report that irrigation [...] Read more.

Melatonin is a pleiotropic signal molecule that plays critical roles in regulating plant growth and development, as well as providing physiological protections against various environmental stresses. Nonetheless, the mechanisms for melatonin-mediated pollen thermotolerance remain largely unknown. In this study, we report that irrigation treatment with melatonin (20 µM) effectively ameliorated high temperature-induced inactivation of pollen and inhibition of pollen germination in tomato (Solanum lycopersicum) plants. Melatonin alleviated reactive oxygen species production in tomato anthers under high temperature by the up-regulation of the transcription and activities of several antioxidant enzymes. Transmission electron micrograph results showed that high temperature-induced pollen abortion is associated with a premature degeneration of the tapetum cells and the formation of defective pollen grains with degenerated nuclei at the early uninuclear microspore stage, whilst melatonin protected degradation of organelles by enhancing the expression of heat shock protein genes to refold unfolded proteins and the expression of autophagy-related genes and formation of autophagosomes to degrade denatured proteins. These findings suggest a novel function of melatonin to protect pollen activity under high temperature and support the potential effects of melatonin on reproductive development of plants. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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15 pages, 4517 KiB

Open AccessArticle

Exogenous Melatonin Mitigates Acid Rain Stress to Tomato Plants through Modulation of Leaf Ultrastructure, Photosynthesis and Antioxidant Potential

by Biswojit Debnath^1,2

, Mubasher Hussain¹

, Muhammad Irshad¹, Sangeeta Mitra¹, Min Li¹, Shuang Liu¹ and Dongliang Qiu^1,*

¹ College of Horticulture, Fujian Agriculture and Forestry University, Fuzhou 350002, China

² Department of Horticulture, Sylhet Agricultural University, Sylhet 3100, Bangladesh

Molecules 2018, 23(2), 388; https://doi.org/10.3390/molecules23020388 - 11 Feb 2018

Cited by 85 | Viewed by 8165

Abstract

Acid rain (AR) is a serious global environmental issue causing physio-morphological changes in plants. Melatonin, as an indoleamine molecule, has been known to mediate many physiological processes in plants under different kinds of environmental stress. However, the role of melatonin in acid rain [...] Read more.

Acid rain (AR) is a serious global environmental issue causing physio-morphological changes in plants. Melatonin, as an indoleamine molecule, has been known to mediate many physiological processes in plants under different kinds of environmental stress. However, the role of melatonin in acid rain stress tolerance remains inexpressible. This study investigated the possible role of melatonin on different physiological responses involving reactive oxygen species (ROS) metabolism in tomato plants under simulated acid rain (SAR) stress. SAR stress caused the inhibition of growth, damaged the grana lamella of the chloroplast, photosynthesis, and increased accumulation of ROS and lipid peroxidation in tomato plants. To cope the detrimental effect of SAR stress, plants under SAR condition had increased both enzymatic and nonenzymatic antioxidant substances compared with control plants. But such an increase in the antioxidant activities were incapable of inhibiting the destructive effect of SAR stress. Meanwhile, melatonin treatment increased SAR-stress tolerance by repairing the grana lamella of the chloroplast, improving photosynthesis and antioxidant activities compared with those in SAR-stressed plants. However, these possible effects of melatonin are dependent on concentration. Moreover, our study suggests that 100-μM melatonin treatment improved the SAR-stress tolerance by increasing photosynthesis and ROS scavenging antioxidant activities in tomato plants. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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13 pages, 4853 KiB

Open AccessArticle

The Complete Chloroplast Genome of a Key Ancestor of Modern Roses, Rosa chinensis var. spontanea, and a Comparison with Congeneric Species

by Hong-Ying Jian^1,*,†

, Yong-Hong Zhang^2,†, Hui-Jun Yan¹, Xian-Qin Qiu¹, Qi-Gang Wang¹, Shu-Bin Li¹ and Shu-Dong Zhang^3,*

¹ National Engineering Research Center for Ornamental Horticulture/Flower Research Institute, Yunnan Academy of Agricultural Sciences, Kunming 650205, China

² School of Life Sciences, Yunnan Normal University, Kunming 650500, China

³ School of Biological Sciences and Technology, Liupanshui Normal University, Liupanshui 553004, China

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 389; https://doi.org/10.3390/molecules23020389 - 12 Feb 2018

Cited by 43 | Viewed by 4835

Abstract

Rosa chinensis var. spontanea, an endemic and endangered plant of China, is one of the key ancestors of modern roses and a source for famous traditional Chinese medicines against female diseases, such as irregular menses and dysmenorrhea. In this study, the complete [...] Read more.

Rosa chinensis var. spontanea, an endemic and endangered plant of China, is one of the key ancestors of modern roses and a source for famous traditional Chinese medicines against female diseases, such as irregular menses and dysmenorrhea. In this study, the complete chloroplast (cp) genome of R. chinensis var. spontanea was sequenced, analyzed, and compared to congeneric species. The cp genome of R. chinensis var. spontanea is a typical quadripartite circular molecule of 156,590 bp in length, including one large single copy (LSC) region of 85,910 bp and one small single copy (SSC) region of 18,762 bp, separated by two inverted repeat (IR) regions of 25,959 bp. The GC content of the whole genome is 37.2%, while that of LSC, SSC, and IR is 42.8%, 35.2% and 31.2%, respectively. The genome encodes 129 genes, including 84 protein-coding genes (PCGs), 37 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. Seventeen genes in the IR regions were found to be duplicated. Thirty-three forward and five inverted repeats were detected in the cp genome of R. chinensis var. spontanea. The genome is rich in SSRs. In total, 85 SSRs were detected. A genome comparison revealed that IR contraction might be the reason for the relatively smaller cp genome size of R. chinensis var. spontanea compared to other congeneric species. Sequence analysis revealed that the LSC and SSC regions were more divergent than the IR regions within the genus Rosa and that a higher divergence occurred in non-coding regions than in coding regions. A phylogenetic analysis showed that the sampled species of the genus Rosa formed a monophyletic clade and that R. chinensis var. spontanea shared a more recent ancestor with R. lichiangensis of the section Synstylae than with R. odorata var. gigantea of the section Chinenses. This information will be useful for the conservation genetics of R. chinensis var. spontanea and for the phylogenetic study of the genus Rosa, and it might also facilitate the genetics and breeding of modern roses. Full article

(This article belongs to the Section Molecular Diversity)

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13 pages, 3556 KiB

Open AccessArticle

Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation

by Yiding Wang^†, Jing Zhang^†, Denghong Zhang, Huixiang Xiao, Shengwei Xiong and Chunhong Huang^*

¹ School of Basic Medical Sciences, Nanchang University, Nanchang 330006, China

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 391; https://doi.org/10.3390/molecules23020391 - 12 Feb 2018

Cited by 60 | Viewed by 5964 | Correction

Abstract

Phospholipase A₂s (PLA₂) is a major component of snake venom with diverse pathologic toxicities and, therefore, a potential target for antivenom therapy. Varespladib was initially designed as an inhibitor of mammal PLA₂s, and was recently repurposed to [...] Read more.

Phospholipase A₂s (PLA₂) is a major component of snake venom with diverse pathologic toxicities and, therefore, a potential target for antivenom therapy. Varespladib was initially designed as an inhibitor of mammal PLA₂s, and was recently repurposed to a broad-spectrum inhibitor of PLA₂ in snake venom. To evaluate the protective abilities of varespladib to hemorrhage, myonecrosis, and systemic toxicities that are inflicted by different crude snake venoms, subcutaneous ecchymosis, muscle damage, and biochemical variation in serum enzymes derived from the envenomed mice were determined, respectively. Varespladib treatment showed a significant inhibitory effect to snake venom PLA₂, which was estimated by IC₅₀ in vitro and ED₅₀ in vivo. In animal models, the severely hemorrhagic toxicity of D. acutus and A. halys venom was almost fully inhibited after administration of varespladib. Moreover, signs of edema in gastrocnemius muscle were remarkably attenuated by administration of varespladib, with a reduced loss of myonecrosis and desmin. Serum levels of creatine kinase, lactate dehydrogenase isoenzyme 1, aspartate transaminase, and alanine transaminase were down-regulated after treatment with varespladib, which indicated the protection to viscera injury. In conclusion, varespladib may be a potential first-line drug candidate in snakebite envenomation first aid or clinical therapy. Full article

(This article belongs to the Special Issue Natural Toxins/Molecules (and Derivatives) from Animal Venoms: From Basic Research to Therapeutic Applications)

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15 pages, 906 KiB

Open AccessArticle

In Vitro and In Vivo Antioxidant Activities of the Flowers and Leaves from Paeonia rockii and Identification of Their Antioxidant Constituents by UHPLC-ESI-HRMSⁿ via Pre-Column DPPH Reaction

by Yating Bao¹, Yan Qu^2,*, Jinhua Li¹, Yanfang Li¹, Xiaodong Ren³, Katherine G. Maffucci⁴, Ruiping Li⁵, Zhanguo Wang⁵ and Rui Zeng^1,*

¹ College of Pharmacy, Southwest Minzu University, Chengdu 610041, China

² Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China

³ College of Chemistry, University of California-Riverside, Riverside, CA 92521, USA

⁴ Department of Chemistry, Stony Brook University, Stony Brook, NY 11794, USA

⁵ Metabonomics Synergy Innovation Laboratory, School of Medicine and Nursing, Chengdu University, Chengdu 610106, China

Molecules 2018, 23(2), 392; https://doi.org/10.3390/molecules23020392 - 12 Feb 2018

Cited by 41 | Viewed by 4818

Abstract

The genus Paeonia, also known as the “King of Flowers” in China, is an important source of traditional Chinese medicine (TCM). Plants of this genus have been used to treat a range of cardiovascular and gynecological diseases. However, the potential pharmacological activity [...] Read more.

The genus Paeonia, also known as the “King of Flowers” in China, is an important source of traditional Chinese medicine (TCM). Plants of this genus have been used to treat a range of cardiovascular and gynecological diseases. However, the potential pharmacological activity of one particular species, Paeonia rockii, has not been fully investigated. In the first part of the present study, 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS), reducing power assays, and metal ion chelating assays were used to investigate the in vitro antioxidant activities of Paeonia rockii. In the second portion of the study, a mouse model of d-galactose-induced aging was used to validate the antioxidant effects of the flowers from Paeonia rockii in vivo. Lastly, potential antioxidant constituents were screened and identified by ultra-high pressure liquid chromatography and electrospray ionization coupled with high-resolution mass spectrometry (UHPLC-ESI-HRMSⁿ) combined with the DPPH assay. Results indicated that the flowers and leaves exhibited stronger antioxidant activity than ascorbic acid in vitro. The therapeutic effect of Paeonia rockii was determined in relation to the levels of biochemical indicators, such as 8-iso-prostaglandin F_2α (8-iso PGF_2α) in the serum, superoxide dismutase (SOD), protein carbonyl, malondialdehyde (MDA), and glutathione (GSH) in the liver and brain, after daily intra-gastric administration of different concentrations of extracts (100, 200 and 400 mg/kg) for three weeks. The levels of 8-iso PGF_2α (p < 0.01) and protein carbonyl groups (p < 0.01) were significantly reduced, whereas those of SOD (p < 0.05) had significantly increased, indicating that components of the flowers of Paeonia rockii had favorable antioxidant activities in vivo. Furthermore, UHPLC-ESI-HRMSⁿ, combined with pre-column DPPH reaction, detected 25 potential antioxidant compounds. Of these, 18 compounds were tentatively identified, including 11 flavonoids, four phenolic acids, two tannins, and one monoterpene glycoside. This study concluded that the leaves and flowers from Paeonia rockii possess excellent antioxidant properties, highlighting their candidacy as “new” antioxidants, which can be utilized therapeutically to protect the body from diseases caused by oxidative stress. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 3676 KiB

Open AccessArticle

Molecular and Functional Properties of Protein Fractions and Isolate from Cashew Nut (Anacardium occidentale L.)

by Cheng-mei Liu, Qian Peng, Jun-zhen Zhong, Wei Liu, Ye-jun Zhong^* and Fang Wang

State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, No. 235 Nanjing East Road, Nanchang 330047, China

Molecules 2018, 23(2), 393; https://doi.org/10.3390/molecules23020393 - 12 Feb 2018

Cited by 73 | Viewed by 8725

Abstract

Some molecular and functional properties of albumin (83.6% protein), globulin (95.5% protein), glutelin (81.3% protein) as well as protein isolate (80.7% protein) from cashew nut were investigated. These proteins were subjected to molecular (circular dichroism, gel electrophoresis, scanning electron microscopy) and functional (solubility, [...] Read more.

Some molecular and functional properties of albumin (83.6% protein), globulin (95.5% protein), glutelin (81.3% protein) as well as protein isolate (80.7% protein) from cashew nut were investigated. These proteins were subjected to molecular (circular dichroism, gel electrophoresis, scanning electron microscopy) and functional (solubility, emulsification, foaming, water/oil holding capacity) tests. Cashew nut proteins represent an abundant nutrient with well-balanced amino acid composition and could meet the requirements recommended by FAO/WHO. SDS-PAGE pattern indicated cashew nut proteins were mainly composed of a polypeptide with molecular weight (MW) of 53 kDa, which presented two bands with MW of 32 and 21 kDa under reducing conditions. The far-UV CD spectra indicated that cashew proteins were rich in β-sheets. The surface hydrophobicity of the protein isolate was higher than that of the protein fractions. In pH 7.0, the solubility of protein fractions was above 70%, which was higher than protein isolate at any pH. Glutelin had the highest water/oil holding capacity and foaming properties. Protein isolate displayed better emulsifying properties than protein fractions. In summary, cashew nut kernel proteins have potential as valuable nutrition sources and could be used effectively in the food industry. Full article

(This article belongs to the Collection Advances in Liquid Separation Techniques for Food and Pharmaceutical Analysis)

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8 pages, 1102 KiB

Open AccessArticle

Cytotoxic and Antimicrobial Compounds from the Marine-Derived Fungus, Penicillium Species

by Diaa T. A. Youssef^1,*

and Abdulrahman M. Alahdal²

¹ Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia

² Department of Clinical Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia

Molecules 2018, 23(2), 394; https://doi.org/10.3390/molecules23020394 - 12 Feb 2018

Cited by 26 | Viewed by 4141

Abstract

The organic extract of liquid cultures of the marine-derived Penicillium sp. was investigated. Fractionation of the extracts of the fungus led to the purification and identification of two new compounds, penicillatides A (1) and B (2), together with the [...] Read more.

The organic extract of liquid cultures of the marine-derived Penicillium sp. was investigated. Fractionation of the extracts of the fungus led to the purification and identification of two new compounds, penicillatides A (1) and B (2), together with the previously reported cyclo(R-Pro–S-Phe) (3) and cyclo(R-Pro–R-Phe) (4). The structures of compounds 1–4 were assigned by extensive interpretation of their NMR and high-resolution mass spectrometry (HRMS). The antiproliferative and cytotoxic activities of the compounds against three human cancer cell lines as well as their antimicrobial activity against several pathogens were evaluated. Compounds 2–4 displayed variable cytotoxic and antimicrobial activities. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 222 KiB

Open AccessArticle

Activity of Salvia dolomitica and Salvia somalensis Essential Oils against Bacteria, Molds and Yeasts

by Valentina Virginia Ebani^1,2,*, Simona Nardoni^1,2

, Fabrizio Bertelloni¹

, Silvia Giovanelli³, Barbara Ruffoni⁴, Carlo D’Ascenzi¹, Luisa Pistelli^2,3

and Francesca Mancianti^1,2

¹ Department of Veterinary Science, University of Pisa, Viale delle Piagge 2, 56124 Pisa, Italy

² Centro Interdipartimentale di Ricerca “Nutraceutica e Alimentazione per la Salute”, University of Pisa, Via del Borghetto 80, 56124 Pisa, Italy

³ Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy

⁴ Centro di Ricerca Orticoltura e Florovivaismo (CREA), Corso Degli Inglesi 508, 18038 Sanremo, Italy

Molecules 2018, 23(2), 396; https://doi.org/10.3390/molecules23020396 - 13 Feb 2018

Cited by 17 | Viewed by 4754

Abstract

Essential oils (EOs) from Salvia dolomitica and Salvia somalensis, widely employed in the cosmetic and perfume industry, were analyzed for composition and tested against bacterial and fungal pathogens isolated from clinical and environmental specimens. The analyses were carried out against Staphylococcus aureus [...] Read more.

Essential oils (EOs) from Salvia dolomitica and Salvia somalensis, widely employed in the cosmetic and perfume industry, were analyzed for composition and tested against bacterial and fungal pathogens isolated from clinical and environmental specimens. The analyses were carried out against Staphylococcus aureus, Staphylococcus pseudointermedius, Pseudomonas aeruginosa, Escherichia coli, Streptococcus canis, Streptococcus pyogenes, Klebsiella pneumoniae, Proteus mirabilis, Microsporum canis, Microsporum gypseum, Trichophyton mentagrophytes, Aspergillus niger, Aspergillus flavus, Candida albicans, Candida krusei, Mucor sp. and Trichothecium roseum. Both EOs showed similar percentages of total monoterpenes and sesquiterpene hydrocarbons. The main constituents were 1,8-cineole and β-caryophyllene in S. dolomitica and bornyl acetate and camphor in S. somalensis. The selected EOs have no relevant antifungal or antibacterial activities if compared to conventional drugs. Full article

(This article belongs to the Special Issue Essential Oils as Antimicrobial and Anti-infectious Agents)

14 pages, 4699 KiB

Open AccessArticle

Enhancing the Bioconversion of Azelaic Acid to Its Derivatives by Response Surface Methodology

by Nurshafira Khairudin¹, Mahiran Basri^1,*, Hamid Reza Fard Masoumi^2,*, Shazwani Samson¹ and Siti Efliza Ashari^1,*

¹ Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia

² Department of Biomaterials, Iran Polymer and Petrochemical Institute, Tehran 14977-13115, Iran

Molecules 2018, 23(2), 397; https://doi.org/10.3390/molecules23020397 - 13 Feb 2018

Cited by 17 | Viewed by 6470

Abstract

Azelaic acid (AzA) and its derivatives have been known to be effective in the treatment of acne and various cutaneous hyperpigmentary disorders. The esterification of azelaic acid with lauryl alcohol (LA) to produce dilaurylazelate using immobilized lipase B from Candida antarctica (Novozym 435) [...] Read more.

Azelaic acid (AzA) and its derivatives have been known to be effective in the treatment of acne and various cutaneous hyperpigmentary disorders. The esterification of azelaic acid with lauryl alcohol (LA) to produce dilaurylazelate using immobilized lipase B from Candida antarctica (Novozym 435) is reported. Response surface methodology was selected to optimize the reaction conditions. A well-fitting quadratic polynomial regression model for the acid conversion was established with regards to several parameters, including reaction time and temperature, enzyme amount, and substrate molar ratios. The regression equation obtained by the central composite design of RSM predicted that the optimal reaction conditions included a reaction time of 360 min, 0.14 g of enzyme, a reaction temperature of 46 °C, and a molar ratio of substrates of 1:4.1. The results from the model were in good agreement with the experimental data and were within the experimental range (R² of 0.9732).The inhibition zone can be seen at dilaurylazelate ester with diameter 9.0±0.1 mm activities against Staphylococcus epidermidis S273. The normal fibroblasts cell line (3T3) was used to assess the cytotoxicity activity of AzA and AzA derivative, which is dilaurylazelate ester. The comparison of the IC₅₀ (50% inhibition of cell viability) value for AzA and AzA derivative was demonstrated. The IC₅₀ value for AzA was 85.28 μg/mL, whereas the IC₅₀ value for AzA derivative was more than 100 μg/mL. The 3T3 cell was still able to survive without any sign of toxicity from the AzA derivative; thus, it was proven to be non-toxic in this MTT assay when compared with AzA. Full article

(This article belongs to the Special Issue Lipases and Lipases Modification)

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20 pages, 463 KiB

Open AccessArticle

Probiotic Properties of Exopolysaccharide-Producing Lactobacillus Strains Isolated from Tempoyak

by Eilaf Suliman Khalil^1,2

, Mohd Yazid Abd Manap^1,3,*, Shuhaimi Mustafa^3,4, Amaal M. Alhelli⁵ and Parisa Shokryazdan⁶

¹ Department of Food Technology, Faculty of Food Science and Technology, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia

² Department of Dairy Production, University of Khartoum, Khartoum North 13314, Khartoum, Sudan

³ Halal Products Research Institute, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia

⁴ Department of Microbiology, Faculty of Biotechnology and Biomolecular Science, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia

⁵ Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia

⁶ Agriculture Biotechnology Research Institute of Iran (ABRII), East and North-East Branch, P.O. Box 91735/844, Mashhad, Iran

Molecules 2018, 23(2), 398; https://doi.org/10.3390/molecules23020398 - 13 Feb 2018

Cited by 92 | Viewed by 8002

Abstract

Tempoyak is a functional Malaysian food (an acid-fermented condiment) which is produced from the pulp of the durian (Durio zibethinus) fruit. The current study aimed to isolate and identify potential exopolysaccharide (EPS)-producing Lactobacillus strains from tempoyak for potential use as probiotics. [...] Read more.

Tempoyak is a functional Malaysian food (an acid-fermented condiment) which is produced from the pulp of the durian (Durio zibethinus) fruit. The current study aimed to isolate and identify potential exopolysaccharide (EPS)-producing Lactobacillus strains from tempoyak for potential use as probiotics. Seven isolates (DUR2, DUR4, DUR5, DUR8, DUR12, DUR18, and DUR20) out of 44 were able to produce EPS, and exhibited resistance to acid and bile salt compared to the reference strains Lactobacillus rhmnosus (ATCC53103) and L. plantarum (ATCC8014). The seven isolated strains belonged to five different species—L. plantarum, L. fermentum, L. crispatus, L. reuteri, and L. pentosus—which were identified using API 50 CHL and 16S rRNA gene sequences (Polymerase chain reaction, PCR – based). The seven strains displayed different ability to produce EPS (100–850 mg/L). Isolates exhibited a high survivability to acid (pH 3.0), bile salts (0.3%), and gastrointestinal tract model (<70%). Results showed that the auto-aggregation and cell surface hydrophobicity ranged from 39.98% to 60.09% and 50.80% to 80.53%, respectively, whereas, the highest co-aggregation value (66.44%) was observed by L. fermentum (DUR8) with Pseudomonas aeruginosa. The isolates showed good inhibitory activity against tested pathogens, high antioxidant activity (32.29% to 73.36%), and good ability to reduce cholesterol (22.55% to 75.15%). Thus, the seven tested strains have value as probiotics. Full article

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18 pages, 1873 KiB

Open AccessArticle

The Antioxidant and Xanthine Oxidase Inhibitory Activity of Plumeria rubra Flowers

by Siti Sarwani Putri Mohamed Isa

, Abdulwali Ablat and Jamaludin Mohamad^*

Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia

Molecules 2018, 23(2), 400; https://doi.org/10.3390/molecules23020400 - 13 Feb 2018

Cited by 46 | Viewed by 6729

Abstract

Plumeria rubra Linn of the family Apocynaceae is locally known in Malaysia as “Kemboja”. It has been used by local traditional medicine practitioners for the treatment of arthritis-related disease. The LCMS/MS analysis of the methanol extract of flowers (PR-ME) showed that it contains [...] Read more.

Plumeria rubra Linn of the family Apocynaceae is locally known in Malaysia as “Kemboja”. It has been used by local traditional medicine practitioners for the treatment of arthritis-related disease. The LCMS/MS analysis of the methanol extract of flowers (PR-ME) showed that it contains 3-O-caffeyolquinic acid, 5-caffeoquinic acid, 1,3-dicaffeoquinic acid, chlorogenic acid, citric acid, 3,3-di-O-methylellagic acid, kaempferol-3-O-glucoside, kaempferol-3-rutinoside, kaempferol, quercetin 3-O-α-l-arabinopyranoside, quercetin, quinic acid and rutin. The flower PR-ME contained high amounts of phenol and flavonoid at 184.632 mg GAE/g and 203.2.2 mg QE/g, respectively. It also exhibited the highest DPPH, FRAP, metal chelating, hydrogen peroxide, nitric oxide superoxide radical scavenging activity. Similarly, the XO inhibitory activity in vitro assay possesses the highest inhibition effects at an IC₅₀ = 23.91 μg/mL. There was no mortality or signs of toxicity in rats at a dose of 4 g/kg body weight. The administration of the flower PR-ME at doses of 400 mg/kg to the rats significantly reduced serum uric acid 43.77%. Similarly, the XO activity in the liver was significantly inhibited by flower PR-ME at doses of 400 mg/kg. These results confirm that the flower PR-ME of P. rubra contains active phytochemical compounds as detected in LCMS/MS that contribute to the inhibition of XO activity in vitro and in vivo in reducing acid uric level in serum and simultaneously scavenging the free radical to reduce the oxidative stress. Full article

(This article belongs to the Section Natural Products Chemistry)

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8 pages, 1837 KiB

Open AccessArticle

Synthesis, Characterization, and Performance Evaluation of Sulfur-Containing Diphenylamines Based on Intramolecular Synergism

by Jun-Bo He¹

, Hao Shi¹, Yue Wang² and Xin-Lei Gao^2,*

¹ Key Laboratory for Deep Processing of Major Grain and Oil, Ministry of Education, College of Food Science & Engineering, Wuhan Polytechnic University, Wuhan 430023, China

² Department of Chemical and Environmental Engineering, Wuhan Polytechnic University, Wuhan 430023, China

Molecules 2018, 23(2), 401; https://doi.org/10.3390/molecules23020401 - 13 Feb 2018

Cited by 11 | Viewed by 3640

Abstract

To obtain novel structural antioxidants that have different antioxidant mechanisms, four 2-(alkylthio)-N-(4-(phenylamino)phenyl)acetamides 2a–d as dual functional antioxidants are designed, synthesized, and confirmed by ¹H-NMR, FTIR, MS, and elemental analysis. The antioxidant behavior of compounds 2a–d as [...] Read more.

To obtain novel structural antioxidants that have different antioxidant mechanisms, four 2-(alkylthio)-N-(4-(phenylamino)phenyl)acetamides 2a–d as dual functional antioxidants are designed, synthesized, and confirmed by ¹H-NMR, FTIR, MS, and elemental analysis. The antioxidant behavior of compounds 2a–d as additives of base oil triisodecyl trimellitate (TIDTM) is evaluated by non-isothermal and isothermal DSC analyses. The results showed all compounds can greatly increase the incipient oxidation temperature (IOT) and oxidation induction time (OIT) of TIDTM, especially, compound 2c exhibited an OIT value of 72.5 min at 230 °C, which is almost 28 times the length of TIDTM. Moreover, compounds 2a–d do not affect the tribological performance of TIDTM. The mechanism of antioxidants involved an intramolecular synergism are proposed. This work demonstrates compound 2c can be used as a novel potential antioxidant additive of TIDTM; in addition, it would inspire the emergence of highly potent antioxidants with different antioxidant mechanisms. Full article

(This article belongs to the Section Medicinal Chemistry)

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17 pages, 2377 KiB

Open AccessArticle

Comparative Analysis of Chemical Composition, Antioxidant Activity and Quantitative Characterization of Some Phenolic Compounds in Selected Herbs and Spices in Different Solvent Extraction Systems

by Shabnam Sepahpour¹, Jinap Selamat^1,2,*

, Mohd Yazid Abdul Manap^3,4, Alfi Khatib⁵ and Ahmad Faizal Abdull Razis^1,2,6

¹ Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

² Food Safety and Food Integrity (FOSFI), Institute of Tropical Agriculture and Food Security, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

³ Department of Food Technology, Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

⁴ Halal Products Research Institute, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

⁵ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, International Islamic Universiti Malaysia, 25200 Kuantan, Pahang, Malaysia

⁶ Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

Molecules 2018, 23(2), 402; https://doi.org/10.3390/molecules23020402 - 13 Feb 2018

Cited by 142 | Viewed by 13302

Abstract

This study evaluated the efficacy of various organic solvents (80% acetone, 80% ethanol, 80% methanol) and distilled water for extracting antioxidant phenolic compounds from turmeric, curry leaf, torch ginger and lemon grass extracts. They were analyzed regarding the total phenol and flavonoid contents, [...] Read more.

This study evaluated the efficacy of various organic solvents (80% acetone, 80% ethanol, 80% methanol) and distilled water for extracting antioxidant phenolic compounds from turmeric, curry leaf, torch ginger and lemon grass extracts. They were analyzed regarding the total phenol and flavonoid contents, antioxidant activity and concentration of some phenolic compounds. Antioxidant activity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay and the ferric reducing antioxidant power (FRAP) assay. Quantification of phenolic compounds was carried out using high-performance liquid chromatography (HPLC). All the extracts possessed antioxidant activity, however, the different solvents showed different efficiencies in the extraction of phenolic compounds. Turmeric showed the highest DPPH values (67.83–13.78%) and FRAP (84.9–2.3 mg quercetin/g freeze-dried crude extract), followed by curry leaf, torch ginger and lemon grass. While 80% acetone was shown to be the most efficient solvent for the extraction of total phenolic compounds from turmeric, torch ginger and lemon grass (221.68, 98.10 and 28.19 mg GA/g freeze dried crude extract, respectively), for the recovery of phenolic compounds from curry leaf (92.23 mg GA/g freeze-dried crude extract), 80% ethanol was the most appropriate solvent. Results of HPLC revealed that the amount of phenolic compounds varied depending on the types of solvents used. Full article

(This article belongs to the Collection Bioactive Compounds)

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8 pages, 374 KiB

Open AccessCommunication

Effects of Dried Blood Spot Storage on Lipidomic Analysis

by Cinzia Di Marino¹, Anna De Marco²

, Antonio Pisanti³ and Valeria Romanucci^1,*

¹ Department of Chemical Sciences, Complesso Universitario di Monte S. Angelo, University of Napoli Federico II, Via Cintia 4, 80126 Napoli, Italy

² Department of Biology, Complesso Universitario di Monte S. Angelo, University Federico II, Via Cintia 4, 80126 Napoli, Italy

³ Consorzio Interuniversitario Sannio Tech, SS Appia km 256, 82030 Apollosa (BN), Italy

Molecules 2018, 23(2), 403; https://doi.org/10.3390/molecules23020403 - 13 Feb 2018

Cited by 6 | Viewed by 2784

Abstract

During the lipidomic analysis of red blood cell membranes, the distribution and percentage ratios of the fatty acids are measured. Since fatty acids are the key constituents of cell membranes, by evaluating their quantities it possible to understand the general health of the [...] Read more.

During the lipidomic analysis of red blood cell membranes, the distribution and percentage ratios of the fatty acids are measured. Since fatty acids are the key constituents of cell membranes, by evaluating their quantities it possible to understand the general health of the cells and to obtain health indicators of the whole organism. However, because the analysis is precise, it is necessary to ensure that the blood does not undergo significant variations between the point of collection and analysis. The composition of the blood may vary dramatically weeks after collection, hence, here an attempt is made to stabilize these complex matrixes using antioxidants deposited on the paper cards on which the blood itself is deposited. Full article

(This article belongs to the Section Analytical Chemistry)

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11 pages, 2066 KiB

Open AccessArticle

Thermal Decomposition Behavior of Hydroxytyrosol (HT) in Nitrogen Atmosphere Based on TG-FTIR Methods

by Jun-Ling Tu and Jiao-Jiao Yuan^*

Department of Chemical Engineering , School of Chemical Engineering and Energy Technology, Dongguan University of Technology, Dongguan 523808, China

Molecules 2018, 23(2), 404; https://doi.org/10.3390/molecules23020404 - 13 Feb 2018

Cited by 14 | Viewed by 3259

Abstract

The thermal decomposition behavior of olive hydroxytyrosol (HT) was first studied using thermogravimetry (TG). Cracked chemical bond and evolved gas analysis during the thermal decomposition process of HT were also investigated using thermogravimetry coupled with infrared spectroscopy (TG-FTIR). Thermogravimetry-Differential thermogravimetry (TG-DTG) curves revealed [...] Read more.

The thermal decomposition behavior of olive hydroxytyrosol (HT) was first studied using thermogravimetry (TG). Cracked chemical bond and evolved gas analysis during the thermal decomposition process of HT were also investigated using thermogravimetry coupled with infrared spectroscopy (TG-FTIR). Thermogravimetry-Differential thermogravimetry (TG-DTG) curves revealed that the thermal decomposition of HT began at 262.8 °C and ended at 409.7 °C with a main mass loss. It was demonstrated that a high heating rate (over 20 K·min⁻¹) restrained the thermal decomposition of HT, resulting in an obvious thermal hysteresis. Furthermore, a thermal decomposition kinetics investigation of HT indicated that the non-isothermal decomposition mechanism was one-dimensional diffusion (D1), integral form g(x) = x², and differential form f(x) = 1/(2x). The four combined approaches were employed to calculate the activation energy (E = 128.50 kJ·mol⁻¹) and Arrhenius preexponential factor (ln A = 24.39 min⁻¹). In addition, a tentative mechanism of HT thermal decomposition was further developed. The results provide a theoretical reference for the potential thermal stability of HT. Full article

(This article belongs to the Section Physical Chemistry)

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13 pages, 3276 KiB

Open AccessFeature PaperArticle

Polysiloxane/Polystyrene Thermo-Responsive and Self-Healing Polymer Network via Lewis Acid-Lewis Base Pair Formation

by Fernando Vidal

, Huina Lin, Cecilia Morales and Frieder Jäkle^*

Department of Chemistry, Rutgers University-Newark, 73 Warren Street, Newark, NJ 07102, USA

Molecules 2018, 23(2), 405; https://doi.org/10.3390/molecules23020405 - 13 Feb 2018

Cited by 34 | Viewed by 8205

Abstract

The use of thermo-reversible Lewis Pair (LP) interactions in the formation of transient polymer networks is still greatly underexplored. In this work, we describe the synthesis and characterization of polydimethylsiloxane/polystyrene (PDMS/PS) blends that form dynamic Lewis acid-Lewis base adducts resulting in reversible crosslinks. [...] Read more.

The use of thermo-reversible Lewis Pair (LP) interactions in the formation of transient polymer networks is still greatly underexplored. In this work, we describe the synthesis and characterization of polydimethylsiloxane/polystyrene (PDMS/PS) blends that form dynamic Lewis acid-Lewis base adducts resulting in reversible crosslinks. Linear PS containing 10 mol % of di-2-thienylboryl pendant groups randomly distributed was obtained in a two-step one-pot functionalization reaction from silyl-functionalized PS, while ditelechelic PDMS with pyridyl groups at the chain-termini was directly obtained via thiol-ene “click” chemistry from commercially available vinyl-terminated PDMS. The resulting soft gels, formed after mixing solutions containing the PDMS and PS polymers, behave at room temperature as elastomeric solid-like materials with very high viscosity (47,300 Pa·s). We applied rheological measurements to study the thermal and time dependence of the viscoelastic moduli, and also assessed the reprocessability and self-healing behavior of the dry gel. Full article

(This article belongs to the Special Issue Lewis Pair Polymerization for New Reactivity and Structure in Polymer Synthesis)

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20 pages, 2770 KiB

Open AccessArticle

Reduction of Hexavalent Chromium and Detection of Chromate Reductase (ChrR) in Stenotrophomonas maltophilia

by Rosa Baldiris^1,2,*, Natali Acosta-Tapia^1,2, Alfredo Montes^1,3, Jennifer Hernández³ and Ricardo Vivas-Reyes^2,3

¹ Grupo de Microbiología Clínica y Ambiental, Facultad de Ciencias Exactas y Naturales, Programa de Biología, Universidad de Cartagena, Campus San Pablo, Cartagena 130015, Colombia

² Grupo de Investigación CIPTEC, Facultad de Ingeniería, Programa de Ingeniería de Procesos, Fundación Universitaria Tecnológico Comfenalco, Cartagena 130015, Colombia

³ Grupo de Química Cuántica y Teórica, Facultad de Ciencias Exactas y Naturales, Universidad de TCartagena, Campus, San Pablo, Cartagena 130015, Colombia

Molecules 2018, 23(2), 406; https://doi.org/10.3390/molecules23020406 - 13 Feb 2018

Cited by 107 | Viewed by 10715

Abstract

An Gram negative strain of S. maltophilia, indigenous to environments contaminated by Cr(VI) and identified by biochemical methods and 16S rRNA gene analysis, reduced chromate by 100%, 98–99% and 92% at concentrations in the 10–70, 80–300, and 500 mg/L range, respectively at [...] Read more.

An Gram negative strain of S. maltophilia, indigenous to environments contaminated by Cr(VI) and identified by biochemical methods and 16S rRNA gene analysis, reduced chromate by 100%, 98–99% and 92% at concentrations in the 10–70, 80–300, and 500 mg/L range, respectively at pH 7 and temperature 37 °C. Increasing concentrations of Cr(VI) in the medium lowered the growth rate but could not be directly correlated with the amount of Cr(VI) reduced. The strain also exhibited multiple resistance to antibiotics and tolerance and resistance to various heavy metals (Ni, Zn and Cu), with the exception of Hg. Hexavalent chromium reduction was mainly associated with the soluble fraction of the cell evaluated with crude cell-free extracts. A protein of molecular weight around 25 kDa was detected on SDS-PAGE gel depending on the concentration of hexavalent chromium in the medium (0, 100 and 500 mg/L). In silico analysis in this contribution, revealed the presence of the chromate reductase gene ChrR in S. maltophilia, evidenced through a fragment of around 468 bp obtained experimentally. High Cr(VI) concentration resistance and high Cr(VI) reducing ability of the strain make it a suitable candidate for bioremediation. Full article

(This article belongs to the Section Chemical Biology)

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15 pages, 1827 KiB

Open AccessFeature PaperArticle

Synthesis and Evaluation of the Tumor Cell Growth Inhibitory Potential of New Putative HSP90 Inhibitors

by Ana Bizarro^1,2, Diana Sousa^1,3,4, Raquel T. Lima^3,4,5, Loana Musso⁶, Raffaella Cincinelli⁶, Vantina Zuco⁷

, Michelandrea De Cesare⁷, Sabrina Dallavalle^6,* and M. Helena Vasconcelos^1,3,4,*

¹ Department of Biological Sciences, Faculty of Pharmacy of the University of Porto (FFUP), Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal

² Department of Biology, School of Sciences, University of Minho, 4710-057 Braga, Portugal

³ i3S—Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal

⁴ Cancer Drug Resistance Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal

⁵ Department of Pathology, Faculty of Medicine of the University of Porto (FMUP), Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal

⁶ Department of Food, Environmental and Nutritional Sciences Division of Chemistry and Molecular Biology, Università degli Studi di Milano, via Celoria 2, 20133 Milano, Italy

⁷ Department of Experimental Oncology and Molecular Medicine, Fondazione, IRCCS—Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milano, Italy

Molecules 2018, 23(2), 407; https://doi.org/10.3390/molecules23020407 - 13 Feb 2018

Cited by 15 | Viewed by 3328

Abstract

Background: Heat shock protein 90 (HSP90) is a well-known target for cancer therapy. In a previous work, some of us have reported a series of 3-aryl-naphtho[2,3-d]isoxazole-4,9-diones as inhibitors of HSP90. Methods: In the present work, various compounds with new chromenopyridinone and [...] Read more.

Background: Heat shock protein 90 (HSP90) is a well-known target for cancer therapy. In a previous work, some of us have reported a series of 3-aryl-naphtho[2,3-d]isoxazole-4,9-diones as inhibitors of HSP90. Methods: In the present work, various compounds with new chromenopyridinone and thiochromenopyridinone scaffolds were synthesized as potential HSP90 inhibitors. Their binding affinity to HSP90 was studied in vitro. Selected compounds (5 and 8) were further studied in various tumor cell lines regarding their potential to cause cell growth inhibition, alter the cell cycle profile, inhibit proliferation, and induce apoptosis. Their effect on HSP90 client protein levels was also confirmed in two cell lines. Finally, the antitumor activity of compound 8 was studied in A431 squamous cell carcinoma xenografts in nude mice. Results: Our results indicated that treatment with compounds 5 and 8 decreased the proliferation of tumor cell lines and compound 8 induced apoptosis. In addition, these two compounds were able to downregulate selected proteins known as “clients” of HSP90. Finally, treatment of xenografted mice with compound 5 resulted in a considerable dose-dependent inhibition of tumor growth. Conclusions: Our results show that two new compounds with a chromenopyridinone and thiochromenopyridinone scaffold are promising putative HSP90 inhibitors causing tumor cell growth inhibition. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 1798 KiB

Open AccessArticle

Novel Conjugated Polymers Prepared by Direct (Hetero) arylation: An Eco-Friendly Tool for Organic Electronics

by Fuchuan Liu¹, Yangqian Zhang¹, Hang Wang¹ and Shiming Zhang^1,2,*

¹ Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University (Nanjing Tech), 30 South Puzhu Road, Nanjing 211816, China

² Nanjing Kuo Hua Electronics Technology Pte. Ltd., Innovation Building B816, Xinmofan Road 5, Nanjing 210009, China

Molecules 2018, 23(2), 408; https://doi.org/10.3390/molecules23020408 - 13 Feb 2018

Cited by 10 | Viewed by 5296

Abstract

The phthalimide (PhI) moiety has been attracting more attention as an excellent acceptor building block in donor-acceptor (D-A) conjugated polymers. In this paper; three D-A conjugated polymers with or without thiocarbonyl moieties are successfully prepared by the direct (hetero)-arylation polymerization (DHAP), which is [...] Read more.

The phthalimide (PhI) moiety has been attracting more attention as an excellent acceptor building block in donor-acceptor (D-A) conjugated polymers. In this paper; three D-A conjugated polymers with or without thiocarbonyl moieties are successfully prepared by the direct (hetero)-arylation polymerization (DHAP), which is an atom efficient and facile synthetic strategy to obtain polymer materials. Compared with the traditional carbon-carbon coupling reactions, this method possesses more advantages, including: fewer synthetic steps, avoidance of the preparation of the organometallic reagents, higher atom economy and fewer toxic byproducts, better compatibility with chemically sensitive functional groups and so on. All three of these designed PhI-based polymers exhibited favourable optoelectronic and thermal performance. The optical, thermodynamic and electrochemical properties of the synthesized polymers were systematically investigated using ultraviolet-visible (UV-vis) spectroscopy, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and cyclic voltammetry (CV). The results of these three polymers indicated that thionation of the carbonyl was a highly effective methods to improve the properties of PhI-based polymers; and provided impetus for the development of thionated PhI derivatives for organic electronic applications. Full article

(This article belongs to the Special Issue Direct (Hetero)Arylation: A New Tool for Organic Electronics)

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15 pages, 1322 KiB

Open AccessFeature PaperArticle

Phytochemical Analysis, Antioxidant and Antimicrobial Activities of Helichrysum arenarium (L.) Moench. and Antennaria dioica (L.) Gaertn. Flowers

by Mihai Babotă¹, Andrei Mocan¹, Laurian Vlase^2,*

, Ovidiu Crișan^3,*, Irina Ielciu¹

, Ana-Maria Gheldiu², Dan Cristian Vodnar⁴

, Gianina Crișan^1,† and Ramona Păltinean^1,†

¹ Department of Pharmaceutical Botany, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania

² Department of Pharmaceutical Technology and Biopharmaceutics, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400010 Cluj-Napoca, Romania

³ Department of Organic Chemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400010 Cluj-Napoca, Romania

⁴ Department of Food Science, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 409; https://doi.org/10.3390/molecules23020409 - 13 Feb 2018

Cited by 57 | Viewed by 8180

Abstract

Antennaria dioica (L.) Gaertn. and Helichrysum arenarium (L.) Moench. are two species of the Asteraceae family, known in Romanian traditional medicine for their diuretic, choleretic, and anti-inflammatory properties. The aim of the present study was to evaluate the phenolic and sterolic composition of [...] Read more.

Antennaria dioica (L.) Gaertn. and Helichrysum arenarium (L.) Moench. are two species of the Asteraceae family, known in Romanian traditional medicine for their diuretic, choleretic, and anti-inflammatory properties. The aim of the present study was to evaluate the phenolic and sterolic composition of flowers from the two species and to assess their antioxidant, antibacterial and antifungal properties. LC-MS analyses were performed on methanolic, ethanolic and 70% v/v ethanolic extracts, before and after acid hydrolysis, and revealed high amounts of polyphenols. Chlorogenic acid was found as the main compound for the flowers of A. dioica (502.70 ± 25.11 mg/100 g d.w.), while quercitrin was dominant in H. arenarium (424.28 ± 21.21 mg/100 g d.w.) in 70% v/v ethanolic extracts before hydrolysis. Antioxidant capacity assays showed an important antioxidant potential, which can be correlated with the determined polyphenolic compounds, showing the 70% v/v ethanolic extracts of the two species as being the most effective antioxidant samples for the DPPH assay. Antibacterial and antifungal assays confirm a modest biological potential for the same extract of both species. Results obtained in the present study bring important data and offer scientific evidence on the chemical composition and on the biological activities of the flowers belonging to the two species. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 444 KiB

Open AccessFeature PaperArticle

Ent-Clerodane Diterpenes from the Bark of Croton oligandrus Pierre ex Hutch. and Assessment of Their Cytotoxicity against Human Cancer Cell Lines

by Stephanie Tamdem Guetchueng, Lutfun Nahar, Kenneth James Ritchie, Fyaz Mahmood Daud Ismail, Andrew Robert Evans and Satyajit Dey Sarker^*

Medicinal Chemistry and Natural Products Research Group, School of Pharmacy and Biomolecular Sciences, Faculty of Science, Liverpool John Moores University, Liverpool L3 3AF, UK

Molecules 2018, 23(2), 410; https://doi.org/10.3390/molecules23020410 - 13 Feb 2018

Cited by 16 | Viewed by 3484

Abstract

New clerodane diterpenes, 12-epi-megalocarpodolide D (2) and an epimeric mixture of crotonolins A (3) and B (4), were isolated from the bark of Croton oligandrus following a bioassay-guided isolation protocol. Known compounds, megalocarpodolide D ( [...] Read more.

New clerodane diterpenes, 12-epi-megalocarpodolide D (2) and an epimeric mixture of crotonolins A (3) and B (4), were isolated from the bark of Croton oligandrus following a bioassay-guided isolation protocol. Known compounds, megalocarpodolide D (1), 12-epi-crotocorylifuran (5), cluytyl-ferulate (6), hexacosanoyl- ferulate (7), vanillin (8), acetyl-aleuritolic acid (9) and lupeol (10), were also isolated. The structures of the isolated compounds (1–10) were elucidated by spectroscopic means. The cytotoxicity of compounds 1–10 was assessed against A549, MCF7, PC3 and PNT2 cell lines using the MTT assay. Compounds 1 and 2 showed moderate levels of activity against both A549 and MCF7 cells with 1 being the most active with IC₅₀ values of 63.8 ± 13.8 and 136.2 ± 22.7 µM against A549 and MCF7 cells, respectively. The epimeric mixture of 3 and 4 was moderately active against A549 and PC3 cells (IC₅₀ = 128.6 ± 31.0 and 111.2 ± 2.9 µM, respectively). Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 1917 KiB

Open AccessArticle

On the Reaction Mechanism of the 3,4-Dimethoxybenzaldehyde Formation from 1-(3′,4′-Dimethoxyphenyl)Propene

by Sebastián Cuesta¹, Josefa Arias¹, Felipe Gallegos¹, Jans Alzate-Morales^2,*

and Lorena Meneses^1,*

¹ Chemistry Department, Pontifical Catholic University of Equator, Av. 12 de Octubre 1076 y Roca, Quito 170109, Ecuador

² Center for Bioinformatics and Molecular Simulations, Faculty of Engineering, University of Talca, 2 Norte 685, Casilla 721, Talca 3640000, Chile

Molecules 2018, 23(2), 412; https://doi.org/10.3390/molecules23020412 - 14 Feb 2018

Cited by 1 | Viewed by 4999

Abstract

Lignin peroxidase (LiP) is an important enzyme for degrading aromatic hydrocarbons not only in nature but also in industry. In the presence of H₂O₂, this enzyme can easily decompose lignin and analogue compounds under mild conditions. In this reaction [...] Read more.

Lignin peroxidase (LiP) is an important enzyme for degrading aromatic hydrocarbons not only in nature but also in industry. In the presence of H₂O₂, this enzyme can easily decompose lignin and analogue compounds under mild conditions. In this reaction mechanism, LiP catalyzes the C–C cleavage of a propenyl side chain, being able to produce veratraldehyde (VAD) from 1-(3′,4′-dimethoxyphenyl) propene (DMPP). One of the few and complete proposed mechanisms includes several non-enzymatic reactions. In this study, we performed a computational study to gain insight about the non-enzymatic steps involved in the reaction mechanism of VAD formation from DMPP using LiP as a catalyst. A kinetic characterization of the reaction using the reaction force and the reaction force constant concepts within the density functional theory (DFT) framework is proposed. All theoretical calculations for the reaction pathway were performed using the Minnesota Global Hybrid functional M06-2X and a 6-31++G(d,p) basis set. The complete reaction comprises seven steps (five steps not including LiP as a catalyst), which include radical species formation, bond transformation, water and oxygen addition, atom reordering, and deacetylation. The overall mechanism is an endothermic process with mixed activation energies depending on the four transition states. These results are the first attempt to fully understand the catalytic role of LiP in the degradation of lignin and its aromatic derivative compounds in terms of the electronic structure methods and future hybrid calculation approaches that we have recently been performing. Full article

(This article belongs to the Special Issue The Molecular Electron Density Theory: A Modern View of Molecular Reactivity in Organic Chemistry)

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14 pages, 3197 KiB

Open AccessArticle

Synthesis, Characterization, and Computational Modeling of N-(1-Ethoxyvinyl)pyridinium Triflates, an Unusual Class of Pyridinium Salts

by Jonathan D. Shapiro¹

, Justin C. Sonberg¹, Benjamin C. Schafer¹

, Christopher C. Williams¹

, Hannah R. Ferris¹, Eric W. Reinheimer², Adam W. Van Wynsberghe¹, Charles E. Kriley³

and Max M. Majireck^1,*

¹ Chemistry Department, Hamilton College, 198 College Hill Road, Clinton, NY 13323, USA

² Rigaku Oxford Diffraction, 9009 New Trails Drive, The Woodlands, TX 77381, USA

³ Department of Chemistry, Grove City College, 100 Campus Drive, Grove City, PA 16127, USA

Molecules 2018, 23(2), 413; https://doi.org/10.3390/molecules23020413 - 14 Feb 2018

Cited by 8 | Viewed by 7189

Abstract

N-Substituted pyridinium salts constitute one of the most valuable reagent classes in organic synthesis, due to their versatility and ease of use. Herein we report a preliminary synthesis and detailed structural analysis of several N-(1-ethoxyvinyl)pyridinium triflates, an unusual class of pyridinium [...] Read more.

N-Substituted pyridinium salts constitute one of the most valuable reagent classes in organic synthesis, due to their versatility and ease of use. Herein we report a preliminary synthesis and detailed structural analysis of several N-(1-ethoxyvinyl)pyridinium triflates, an unusual class of pyridinium salts with potentially broad use as a reagent in organic synthesis. Treatment of pyridines with trifluoromethane sulfonic acid and ethoxyacetylene generates stable, isolable adducts which have been extensively characterized, due to their novelty. Three-dimensional structural stability is perpetuated by an array of C–H•••O hydrogen bonds involving oxygen atoms from the –SO₃ groups of the triflate anion, and hydrogen atoms from the aromatic ring and vinyl group of the pyridinium cation. Predictions from density functional theory calculations of the energy landscape for rotation about the exocyclic C–N bond of 2-chloro-1-(1-ethoxyvinyl)pyridine-1-ium trifluoromethanesulfonate (7) and 1-(1-ethoxyvinyl)pyridine-1-ium trifluoromethanesulfonate (16) are also reported. Notably, the predicted global energy minimum of 7 was nearly identical to that found within the crystal structure. Full article

(This article belongs to the Section Organic Chemistry)

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18 pages, 1324 KiB

Open AccessArticle

4-Thiazolidinone Derivatives as MMP Inhibitors in Tissue Damage: Synthesis, Biological Evaluation and Docking Studies

by Matteo Incerti¹

, Lucia Crascì^2,*

, Paola Vicini¹, Esin Aki³

, Ismail Yalcin³, Tugba Ertan-Bolelli³, Venera Cardile⁴, Adriana Carol Eleonora Graziano⁴ and Annamaria Panico²

¹ Department of Food and Drug, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy

² Department of Drug Sciences, University of Catania, V. le A. Doria 6, 95125 Catania, Italy

³ Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ankara University, Tandogan, Ankara 06100, Turkey

⁴ Department of Physiological Sciences, University of Catania, V. le A. Doria 6, 95125 Catania, Italy

Molecules 2018, 23(2), 415; https://doi.org/10.3390/molecules23020415 - 14 Feb 2018

Cited by 11 | Viewed by 4866

Abstract

Nine 2-(1,2-benzothiazol-3-yl)-N-(4-oxo-2-phenyl-1,3-thiazolidin-3-yl)propanamides combining a benzisothiazole and 4-thiazolidinone in one framework were designed and synthesized. The aim of the study was to verify their effectiveness to affect the inflammatory/oxidative process in which free oxygen and nitrite (ROS and RNS) radicals, inflammatory mediators, [...] Read more.

Nine 2-(1,2-benzothiazol-3-yl)-N-(4-oxo-2-phenyl-1,3-thiazolidin-3-yl)propanamides combining a benzisothiazole and 4-thiazolidinone in one framework were designed and synthesized. The aim of the study was to verify their effectiveness to affect the inflammatory/oxidative process in which free oxygen and nitrite (ROS and RNS) radicals, inflammatory mediators, such as nuclear factor κB (NF-κB), and matrix metalloproteinases (MMPs) are involved. Docking studies of all the compounds were performed in order to explore their binding mode at the MMP-9 protein. An appreciable anti-inflammatory/potential wound healing effects of the tested compounds was highlighted. Derivative 23, bearing a 4-carboxyphenyl substituent at C2 of the 4-thiazolidinone ring, exhibited the highest activity, being able to inhibit MMP-9 at nanomolar level(IC₅₀ = 40 nM). Full article

(This article belongs to the Special Issue Recent Trends on Enzymes Inhibitors and Activators in Drug Research)

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10 pages, 909 KiB

Open AccessArticle

Identification of Bichalcones as Sirtuin Inhibitors by Virtual Screening and In Vitro Testing

by Berin Karaman^1,2,†, Zayan Alhalabi^1,†

, Sören Swyter³, Shetonde O. Mihigo⁴, Kerstin Andrae-Marobela⁵, Manfred Jung³

, Wolfgang Sippl¹

and Fidele Ntie-Kang^1,6,*

¹ Department of Pharmaceutical Chemistry, Martin-Luther University of Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle (Saale), Germany

² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Biruni University, Istanbul 34010, Turkey

³ Institute of Pharmaceutical Sciences, Albert-Ludwigs-University of Freiburg, Albertstr. 25, 79104 Freiburg im Breisgau, Germany

⁴ Department of Chemistry, University of Kinshasa, Kinshasa P.O. Box 190 XI, Congo

⁵ Department of Biological Sciences, Faculty of Science, University of Botswana, Block 235, Private Bag, Gaborone 0022, Botswana

⁶ Department of Chemistry, University of Buea, P.O. Box 63, Buea 00237, Cameroon

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 416; https://doi.org/10.3390/molecules23020416 - 14 Feb 2018

Cited by 24 | Viewed by 5290

Abstract

Sirtuins are nicotinamide adenine dinucleotide (NAD⁺)-dependent class III histone deacetylases, which have been linked to the pathogenesis of numerous diseases, including HIV, metabolic disorders, neurodegeneration and cancer. Docking of the virtual pan-African natural products library (p-ANAPL), followed by in vitro testing, [...] Read more.

Sirtuins are nicotinamide adenine dinucleotide (NAD⁺)-dependent class III histone deacetylases, which have been linked to the pathogenesis of numerous diseases, including HIV, metabolic disorders, neurodegeneration and cancer. Docking of the virtual pan-African natural products library (p-ANAPL), followed by in vitro testing, resulted in the identification of two inhibitors of sirtuin 1, 2 and 3 (sirt1–3). Two bichalcones, known as rhuschalcone IV (8) and an analogue of rhuschalcone I (9), previously isolated from the medicinal plant Rhus pyroides, were shown to be active in the in vitro assay. The rhuschalcone I analogue (9) showed the best activity against sirt1, with an IC₅₀ value of 40.8 µM. Based on the docking experiments, suggestions for improving the biological activities of the newly identified hit compounds have been provided. Full article

(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products 2018)

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12 pages, 4111 KiB

Open AccessArticle

Discovery of 2-(4-Substituted-piperidin/piperazine-1-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-quinazoline-2,4-diamines as PAK4 Inhibitors with Potent A549 Cell Proliferation, Migration, and Invasion Inhibition Activity

by Tianxiao Wu, Yu Pang, Jing Guo, Wenbo Yin, Mingyue Zhu, Chenzhou Hao, Kai Wang, Jian Wang, Dongmei Zhao^*

and Maosheng Cheng

Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China

Molecules 2018, 23(2), 417; https://doi.org/10.3390/molecules23020417 - 14 Feb 2018

Cited by 14 | Viewed by 3739

Abstract

A series of novel 2,4-diaminoquinazoline derivatives were designed, synthesized, and evaluated as p21-activated kinase 4 (PAK4) inhibitors. All compounds showed significant inhibitory activity against PAK4 (half-maximal inhibitory concentration IC₅₀ < 1 μM). Among them, compounds 8d and 9c demonstrated the most [...] Read more.

A series of novel 2,4-diaminoquinazoline derivatives were designed, synthesized, and evaluated as p21-activated kinase 4 (PAK4) inhibitors. All compounds showed significant inhibitory activity against PAK4 (half-maximal inhibitory concentration IC₅₀ < 1 μM). Among them, compounds 8d and 9c demonstrated the most potent inhibitory activity against PAK4 (IC₅₀ = 0.060 μM and 0.068 μM, respectively). Furthermore, we observed that compounds 8d and 9c displayed potent antiproliferative activity against the A549 cell line and inhibited cell cycle distribution, migration, and invasion of this cell line. In addition, molecular docking analysis was performed to predict the possible binding mode of compound 8d. This series of compounds has the potential for further development as PAK4 inhibitors for anticancer activity. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 2645 KiB

Open AccessArticle

Development of Functional Phthalocyanine-Based Associate towards an Effective Fluorimetric Detection of Hg(II)

by Guang-Xin Du, Tao Zhou, Meng-Lin Guo, Ping Huang, Ya-Bin Deng and Dong-Hui Li^*

Cancer Research Center, Medical College, Xiamen University, Xiamen 361102, China

Molecules 2018, 23(2), 418; https://doi.org/10.3390/molecules23020418 - 14 Feb 2018

Cited by 2 | Viewed by 3501

Abstract

In acidic media, cationic phthalocyanine Alcian blue 8GX, has an efficient fluorescence quenching effect on anionic phthalocyanine tetrasulphoaluminium phthalocyanines (AlS₄Pc), forming an almost non-fluorescent associate. Based on this discovery, a red-emitting fluorescent probe consisted of AlS₄P_C and Alcian [...] Read more.

In acidic media, cationic phthalocyanine Alcian blue 8GX, has an efficient fluorescence quenching effect on anionic phthalocyanine tetrasulphoaluminium phthalocyanines (AlS₄Pc), forming an almost non-fluorescent associate. Based on this discovery, a red-emitting fluorescent probe consisted of AlS₄P_C and Alcian blue 8GX has been developed through molecular assembly. Further studies indicated that the presence of Hg(II) ion has a significant fluorescence recovery effect of the probe. Notably, only Hg(II) can significantly restore the fluorescence of AlS₄Pc-Alcian blue 8GX system which was revealed from the screening experiments of common metal ions, which confirmed that the fluorescence recovery by other metal ions is very weak or even unrestored, showing high specificity and sensitivity AlS₄Pc-Alcian blue 8GX to Hg(II). Thus, a new fluorimetry for Hg(II) with high specificity and high sensitivity in a wide concentration range has been established using AlS₄P_c-Alcian blue 8GX associate as a red-emitting fluorescent probe. It is more noteworthy that this study opens a new way for development and application of functional phthalocyanine based red-emitting fluorescent probes. Full article

(This article belongs to the Special Issue Advanced Functional Dyes)

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16 pages, 2238 KiB

Open AccessArticle

Half-Sandwich Ru(II) and Os(II) Bathophenanthroline Complexes Containing a Releasable Dichloroacetato Ligand

by Pavel Štarha¹

, Zdeněk Trávníček^1,*

, Ján Vančo¹

and Zdeněk Dvořák²

¹ Department of Inorganic Chemistry & Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University in Olomouc, 17. listopadu 12, 771 46 Olomouc, Czech Republic

² Department of Cell Biology and Genetics & Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University in Olomouc, Šlechtitelů 27, 783 71 Olomouc, Czech Republic

Molecules 2018, 23(2), 420; https://doi.org/10.3390/molecules23020420 - 14 Feb 2018

Cited by 21 | Viewed by 4733

Abstract

We report on the preparation and thorough characterization of cytotoxic half-sandwich complexes [Ru(η⁶-pcym)(bphen)(dca)]PF₆ (Ru-dca) and [Os(η⁶-pcym)(bphen)(dca)]PF₆ (Os-dca) containing dichloroacetate(1–) (dca) as the releasable O-donor [...] Read more.

We report on the preparation and thorough characterization of cytotoxic half-sandwich complexes [Ru(η⁶-pcym)(bphen)(dca)]PF₆ (Ru-dca) and [Os(η⁶-pcym)(bphen)(dca)]PF₆ (Os-dca) containing dichloroacetate(1–) (dca) as the releasable O-donor ligand bearing its own cytotoxicity; pcym = 1-methyl-4-(propan-2-yl)benzene (p-cymene), bphen = 4,7-diphenyl-1,10-phenanthroline (bathophenanthroline). Complexes Ru-dca and Os-dca hydrolyzed in the water-containing media, which led to the dca ligand release (supported by ¹H NMR and electrospray ionization mass spectra). Mass spectrometry studies revealed that complexes Ru-dca and Os-dca do not interact covalently with the model proteins cytochrome c and lysozyme. Both complexes exhibited slightly higher in vitro cytotoxicity (IC₅₀ = 3.5 μM for Ru-dca, and 2.6 μM for Os-dca) against the A2780 human ovarian carcinoma cells than cisplatin (IC₅₀ = 5.9 μM), while their toxicity on the healthy human hepatocytes was found to be IC₅₀ = 19.1 μM for Ru-dca and IC₅₀ = 19.7 μM for Os-dca. Despite comparable cytotoxicity of complexes Ru-dca and Os-dca, both the complexes modified the cell cycle, mitochondrial membrane potential, and mitochondrial cytochrome c release by a different way, as revealed by flow cytometry experiments. The obtained results point out the different mechanisms of action between the complexes. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

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20 pages, 4213 KiB

Open AccessArticle

Modulation of Donor-Acceptor Distance in a Series of Carbazole Push-Pull Dyes; A Spectroscopic and Computational Study

by Joshua J. Sutton¹, Jonathan E. Barnsley¹, Joseph I. Mapley¹, Pawel Wagner^2,3,*, David L. Officer^2,3,* and Keith C. Gordon^1,*

¹ Department of Chemistry, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand

² ARC Centre of Excellence for Electromaterials Science, University of Wollongong, Wollongong, NSW 2522, Australia

³ Intelligent Polymer Research Institute/AIIM Faculty, Innovation Campus, University of Wollongong, Wollongong, NSW 2522, Australia

Molecules 2018, 23(2), 421; https://doi.org/10.3390/molecules23020421 - 14 Feb 2018

Cited by 10 | Viewed by 4956

Abstract

A series of eight carbazole-cyanoacrylate based donor-acceptor dyes were studied. Within the series the influence of modifying the thiophene bridge, linking donor and acceptor and a change in the nature of the acceptor, from acid to ester, was explored. In this joint experimental [...] Read more.

A series of eight carbazole-cyanoacrylate based donor-acceptor dyes were studied. Within the series the influence of modifying the thiophene bridge, linking donor and acceptor and a change in the nature of the acceptor, from acid to ester, was explored. In this joint experimental and computational study we have used electronic absorbance and emission spectroscopies, Raman spectroscopy and computational modeling (density functional theory). From these studies it was found that extending the bridge length allowed the lowest energy transition to be systematically red shifted by 0.12 eV, allowing for limited tuning of the absorption of dyes using this structural motif. Using the aforementioned techniques we demonstrate that this transition is charge transfer in nature. Furthermore, the extent of charge transfer between donor and acceptor decreases with increasing bridge length and the bridge plays a smaller role in electronically mixing with the acceptor as it is extended. Full article

(This article belongs to the Special Issue Advanced Functional Dyes)

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22 pages, 5766 KiB

Open AccessArticle

A Comparative Study of Human Saposins

by María Garrido-Arandia¹, Bruno Cuevas-Zuviría¹, Araceli Díaz-Perales^1,2 and Luis F. Pacios^1,2,*

¹ Centro de Biotecnología y Genómica de Plantas (CBGP, UPM-INIA), Campus de Montegancedo-UPM, 28223 Madrid, Spain

² Departamento de Biotecnología-Biología Vegetal, ETSIAAB, Universidad Politécnica de Madrid (UPM), Ciudad Universitaria, 28040 Madrid, Spain

Molecules 2018, 23(2), 422; https://doi.org/10.3390/molecules23020422 - 14 Feb 2018

Cited by 8 | Viewed by 4289

Abstract

Saposins are small proteins implicated in trafficking and loading of lipids onto Cluster of Differentiation 1 (CD1) receptor proteins that in turn present lipid antigens to T cells and a variety of T-cell receptors, thus playing a crucial role in innate and adaptive [...] Read more.

Saposins are small proteins implicated in trafficking and loading of lipids onto Cluster of Differentiation 1 (CD1) receptor proteins that in turn present lipid antigens to T cells and a variety of T-cell receptors, thus playing a crucial role in innate and adaptive immune responses in humans. Despite their low sequence identity, the four types of human saposins share a similar folding pattern consisting of four helices linked by three conserved disulfide bridges. However, their lipid-binding abilities as well as their activities in extracting, transporting and loading onto CD1 molecules a variety of sphingo- and phospholipids in biological membranes display two striking characteristics: a strong pH-dependence and a structural change between a compact, closed conformation and an open conformation. In this work, we present a comparative computational study of structural, electrostatic, and dynamic features of human saposins based upon their available experimental structures. By means of structural alignments, surface analyses, calculation of pH-dependent protonation states, Poisson-Boltzmann electrostatic potentials, and molecular dynamics simulations at three pH values representative of biological media where saposins fulfill their function, our results shed light into their intrinsic features. The similarities and differences in this class of proteins depend on tiny variations of local structural details that allow saposins to be key players in triggering responses in the human immune system. Full article

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14 pages, 3962 KiB

Open AccessFeature PaperArticle

Microhydration and the Enhanced Acidity of Free Radicals

by John C. Walton

EaStCHEM School of Chemistry, University of St. Andrews, St. Andrews KY16 9ST, UK

Molecules 2018, 23(2), 423; https://doi.org/10.3390/molecules23020423 - 14 Feb 2018

Cited by 7 | Viewed by 4917

Abstract

Recent theoretical research employing a continuum solvent model predicted that radical centers would enhance the acidity (RED-shift) of certain proton-donor molecules. Microhydration studies employing a DFT method are reported here with the aim of establishing the effect of the solvent micro-structure on the [...] Read more.

Recent theoretical research employing a continuum solvent model predicted that radical centers would enhance the acidity (RED-shift) of certain proton-donor molecules. Microhydration studies employing a DFT method are reported here with the aim of establishing the effect of the solvent micro-structure on the acidity of radicals with and without RED-shifts. Microhydration cluster structures were obtained for carboxyl, carboxy-ethynyl, carboxy-methyl, and hydroperoxyl radicals. The numbers of water molecules needed to induce spontaneous ionization were determined. The hydration clusters formed primarily round the CO₂ units of the carboxylate-containing radicals. Only 4 or 5 water molecules were needed to induce ionization of carboxyl and carboxy-ethynyl radicals, thus corroborating their large RED-shifts. Full article

(This article belongs to the Special Issue Radical Chemistry)

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15 pages, 4554 KiB

Open AccessArticle

Gold and Nickel Extended Thiophenic-TTF Bisdithiolene Complexes

by Rafaela A. L. Silva, Bruno J. C. Vieira, Marta M. Andrade, Isabel C. Santos

, Sandra Rabaça

, Elsa B. Lopes, Joana T. Coutinho, Laura C. J. Pereira

, Manuel Almeida

and Dulce Belo^*

C²TN, Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, E.N. 10 ao km 139.7, 2695-066 Bobadela LRS, Portugal

Molecules 2018, 23(2), 424; https://doi.org/10.3390/molecules23020424 - 14 Feb 2018

Cited by 5 | Viewed by 3997

Abstract

Gold and nickel bisdithiolene complexes with methyl and tert-butyl substituted thiophenetetrathiafulavalenedithiolate ligands (α-mtdt and α-tbtdt) were prepared and characterized. These complexes were obtained, under anaerobic conditions, as tetrabutylammonium salts. The diamagnetic gold monoanion (n-Bu₄N)[Au(α-mtdt)₂] (3 [...] Read more.

Gold and nickel bisdithiolene complexes with methyl and tert-butyl substituted thiophenetetrathiafulavalenedithiolate ligands (α-mtdt and α-tbtdt) were prepared and characterized. These complexes were obtained, under anaerobic conditions, as tetrabutylammonium salts. The diamagnetic gold monoanion (n-Bu₄N)[Au(α-mtdt)₂] (3) and nickel dianionic species (n-Bu₄N)_x[Ni(α-mtdt)₂] (x = 1,2) (4) were similar to the related non-substituted extended thiophenic-TTF (TTF = tetrathiafulvalene) bisdithiolenes. However the introduction of the large, bulky substituent tert-butyl, led to the formation of a Au (I) dinuclear complex, (n-Bu₄N)₂[Au₂(α-tbtdt)₂] (5). The neutral methyl substituted gold and nickel complexes were easily obtained through air or iodine exposure as polycrystalline or amorphous fine powder. [Au(α-mtdt)₂] (6) and [Ni(α-mtdt)₂] (7) polycrystalline samples display properties of a metallic system with a room temperature electrical conductivity of 0.32 S/cm and ≈4 S/cm and a thermoelectric power of ≈5 µV/K and ≈32 µV/K, respectively. While [Au(α-mtdt)₂] (6) presented a Pauli-like magnetic susceptibility typical of conducting systems, in [Ni(α-mtdt)₂] (7) large magnetic susceptibilities indicative of high spin states were observed. Both electric transport properties and magnetic properties for gold and nickel [M(α-mtdt)₂] are indicative that these compounds are single component molecular conductors. Full article

(This article belongs to the Special Issue Coordination Chemistry for Devices and Functional Materials)

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15 pages, 2015 KiB

Open AccessArticle

Effect of Atomic Charges on Octanol–Water Partition Coefficient Using Alchemical Free Energy Calculation

by Koji Ogata^*

, Makoto Hatakeyama and Shinichiro Nakamura

RIKEN Innovation Center, Nakamura Laboratory, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan

Molecules 2018, 23(2), 425; https://doi.org/10.3390/molecules23020425 - 15 Feb 2018

Cited by 18 | Viewed by 5272

Abstract

The octanol–water partition coefficient (logP_ow) is an important index for measuring solubility, membrane permeability, and bioavailability in the drug discovery field. In this paper, the logP_ow values of 58 compounds were predicted by alchemical free energy calculation using [...] Read more.

The octanol–water partition coefficient (logP_ow) is an important index for measuring solubility, membrane permeability, and bioavailability in the drug discovery field. In this paper, the logP_ow values of 58 compounds were predicted by alchemical free energy calculation using molecular dynamics simulation. In free energy calculations, the atomic charges of the compounds are always fixed. However, they must be recalculated for each solvent. Therefore, three different sets of atomic charges were tested using quantum chemical calculations, taking into account vacuum, octanol, and water environments. The calculated atomic charges in the different environments do not necessarily influence the correlation between calculated and experimentally measured ∆G_water values. The largest correlation coefficient values of the solvation free energy in water and octanol were 0.93 and 0.90, respectively. On the other hand, the correlation coefficient of logP_ow values calculated from free energies, the largest of which was 0.92, was sensitive to the combination of the solvation free energies calculated from the calculated atomic charges. These results reveal that the solvent assumed in the atomic charge calculation is an important factor determining the accuracy of predicted logP_ow values. Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 423 KiB

Open AccessArticle

Chemical Composition of Pyroligneous Acid Obtained from Eucalyptus GG100 Clone

by Alexandre S. Pimenta¹, Maíra Fasciotti², Thays V. C. Monteiro² and Kássio M. G. Lima^3,*

¹ Agricultural Sciences Academic Unit, Forest Sciences Graduate Program—PPGCFL, Forest, Bioenergy and Environment Research Group, Federal University of Rio Grande do Norte—UFRN, Natal 59280000, Brazil

² National Institute of Metrology, Quality and Technology, Duque de Caxias 25250020, Brazil

³ Institute of Chemistry, Chemistry Graduate Program, Biological Chemistry and Chemometrics Research Group, Federal University of Rio Grande do Norte—UFRN, Natal 59280000, Brazil

Molecules 2018, 23(2), 426; https://doi.org/10.3390/molecules23020426 - 15 Feb 2018

Cited by 56 | Viewed by 5734

Abstract

The present study aimed to characterize the chemical composition of pyroligneous acid (PA) obtained from slow pyrolysis of the clone GG100 of Eucalyptus urophylla × Eucalyptus grandis. The efficiency of extraction of organic compounds by using different solvents—dichloromethane (DCM), diethyl ether (DE) [...] Read more.

The present study aimed to characterize the chemical composition of pyroligneous acid (PA) obtained from slow pyrolysis of the clone GG100 of Eucalyptus urophylla × Eucalyptus grandis. The efficiency of extraction of organic compounds by using different solvents—dichloromethane (DCM), diethyl ether (DE) and ethyl acetate (EA)—was evaluated. Wood discs were collected and carbonized at a heating rate of 1.25 °C/min until 450 °C. Pyrolysis gases were trapped and condensed, yielding a crude liquid product (CLP), which was refined to obtain pure PA. Then liquid–liquid extraction was carried out. Each extracted fraction was analyzed by GC-MS and the chemical compounds were identified. Experimental results showed that a larger number of chemical compounds could be extracted by using DCM and EA in comparison to diethyl ether DE. A total number of 93 compounds were identified, with phenolic compounds being the major group, followed by aldehydes and ketones, furans, pyrans and esters. Higher contents of guaiacol, phenol, cresols and furfural seem to explain the antibacterial and antifungal activity shown by PA, as reported previously in the literature. Experimental data indicated that the organic phase extracted from GG100 PA consists of a mixture of compounds similar to liquid smokes regularly used in the food industry. Full article

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12 pages, 2165 KiB

Open AccessArticle

Comparison of Structural and Functional Properties of Starches from the Rhizome and Bulbil of Chinese Yam (Dioscorea opposita Thunb.)

by Biao Zhang^1,2, Ke Guo^1,2

, Lingshang Lin^1,2 and Cunxu Wei^1,2,*

¹ Key Laboratory of Crop Genetics and Physiology of Jiangsu Province/Key Laboratory of Plant Functional Genomics of the Ministry of Education, Yangzhou University, Yangzhou 225009, China

² Co-Innovation Center for Modern Production Technology of Grain Crops of Jiangsu Province/Joint International Research Laboratory of Agriculture & Agri-Product Safety of the Ministry of Education, Yangzhou University, Yangzhou 225009, China

Molecules 2018, 23(2), 427; https://doi.org/10.3390/molecules23020427 - 15 Feb 2018

Cited by 24 | Viewed by 5245

Abstract

Chinese yam is an important edible starch plant and widely cultivated in China. Its rhizome and bulbil are starch storage tissues below and above ground, respectively. In this paper, starches were isolated from the rhizome and bulbil of Chinese yam, and their structural [...] Read more.

Chinese yam is an important edible starch plant and widely cultivated in China. Its rhizome and bulbil are starch storage tissues below and above ground, respectively. In this paper, starches were isolated from the rhizome and bulbil of Chinese yam, and their structural and functional properties were compared. Both starches had an oval shape with an eccentric hilum and a C_A-type crystalline structure. Their short-range ordered structure and lamellar structure had no significant difference. However, the rhizome starch had a significantly bigger granule size and lower amylose content than the bulbil starch. The swelling power and water solubility were significantly lower in the rhizome starch than in the bulbil starch. The onset and peak gelatinization temperatures were significantly higher in the rhizome starch than in the bulbil starch. The rhizome starch had a significantly higher breakdown viscosity and a lower setback viscosity than the bulbil starch. The thermal stability was lower in the rhizome starch than in the bulbil starch. The rhizome starch had a significantly lower resistance to hydrolysis and in vitro digestion than the bulbil starch. The above results provide important information for the utilization of rhizome and bulbil starches of Chinese yam. Full article

(This article belongs to the Special Issue Polysaccharide-based Materials)

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22 pages, 4346 KiB

Open AccessArticle

Organ-Specific Metabolic Shifts of Flavonoids in Scutellaria baicalensis at Different Growth and Development Stages

by Jingyuan Xu

, Yilan Yu, Ruoyun Shi, Guoyong Xie, Yan Zhu, Gang Wu and Minjian Qin^*

Department of Resources Science of Traditional Chinese Medicines, School of Traditional Chinese Pharmacy and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China

Molecules 2018, 23(2), 428; https://doi.org/10.3390/molecules23020428 - 15 Feb 2018

Cited by 43 | Viewed by 4677

Abstract

Scutellaria baicalensis Georgi is a traditional Chinese herbal medicine mainly containing flavonoids that contribute to its bioactivities. In this study, the distributions and dynamic changes of flavonoid levels in various organs of S. baicalensis at different development stages were investigated by UHPLC-QTOF-MS/MS and [...] Read more.

Scutellaria baicalensis Georgi is a traditional Chinese herbal medicine mainly containing flavonoids that contribute to its bioactivities. In this study, the distributions and dynamic changes of flavonoid levels in various organs of S. baicalensis at different development stages were investigated by UHPLC-QTOF-MS/MS and HPLC-DAD methods. The results indicated that the metabolic profiles of S. baicalensis changed with growth and development. During the initial germination stage, the seeds mainly contained flavonols. With growth, the main kinds of flavonoids in S. baicalensis changed from flavonols to flavanones and flavones. The results also revealed that the accumulation of flavonoids in S. baicalensis is organ-specific. The flavones without 4′-OH groups mainly accumulate in the root and the flavanones mainly accumulate in aerial organs. Dynamic accumulation analysis showed that the main flavonoids in the root of S. baicalensis accumulated rapidly before the full-bloom stage, then changed to a small extent. The results suggested the proper harvest time for the aerial parts was at the initial stage of reproductive growth and the flower buds should be collected before flowering. This study deepening the knowledge of S. baicalensis should provide valuable information for guiding the scientific cultivation of this plant and the development and utilization of S. baicalensis. Full article

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11 pages, 874 KiB

Open AccessArticle

Semi-Preparative Separation of 10 Caffeoylquinic Acid Derivatives Using High Speed Counter-Current Chromatogaphy Combined with Semi-Preparative HPLC from the Roots of Burdock (Arctium lappa L.)

by Zhenjia Zheng¹, Xiao Wang², Pengli Liu¹, Meng Li¹, Hongjing Dong^2,* and Xuguang Qiao^1,*

¹ College of Food Science and Engineering, Shandong Agricultural University, Taian 271018, China

² Key Laboratory of TCM Quality Control Technology, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, China

Molecules 2018, 23(2), 429; https://doi.org/10.3390/molecules23020429 - 15 Feb 2018

Cited by 36 | Viewed by 5192

Abstract

Burdock roots are healthy dietary supplements and a kind of famous traditional Chinese medicine, which contains large amounts of caffeoylquinic acid derivatives. However, little research has been reported on the preparative separation of these compounds from burdock roots. In the present study, a [...] Read more.

Burdock roots are healthy dietary supplements and a kind of famous traditional Chinese medicine, which contains large amounts of caffeoylquinic acid derivatives. However, little research has been reported on the preparative separation of these compounds from burdock roots. In the present study, a combinative method of HSCCC and semi-preparative HPLC was developed for the semi-preparative separation of caffeoylquinic acid derivatives from the burdock roots. The ethyl acetate extract of burdock roots was first fractionated by MCI macroporous resin chromatography and give three fractions (Fr. 1–3) from the elution of 40% methanol. Then, these three fractions (120 mg) were separately subjected to HSCCC for purification with the solvent system composed of petroleum ether-ethyl acetate-methanol-water at different volume ratios, and the mixtures were further purified by semi-preparative HPLC. As a result, a total of eight known caffeoylquinic acid derivatives including 3-O-caffeoylquinic acid (32.7 mg, 95.7%), 1,5-O- dicaffeoylquinic acid (4.3 mg, 97.2%), 3-O-caffeoylquinic acid methyl ester (12.1 mg, 93.2%), 1,3-O-dicaffeoylquinic acid (42.9 mg, 91.1%), 1,5-O-dicaffeoyl-3-O-(4-maloyl)-quinic acid (4.3 mg, 84.5%), 4,5-O-dicaffeoylquinic acid (5.3 mg, 95.5%), 1,5-O-dicaffeoyl-3-O-succinylquinic acid (8.7 mg, 93.4%), and 1,5-O-dicaffeoyl-4-O-succinylquinic acid (1.7 mg, 91.8%), and two new compounds were obtained. The new compounds were 1,4-O-dicaffeoyl-3-succinyl methyl ester quinic acid (14.6 mg, 96.1%) and 1,5-O-dicaffeoyl-3-O-succinyl methyl ester quinic acid (3.1 mg, 92.6%), respectively. The research indicated that the combination of HSCCC and semi-preparative HPLC is a highly efficient approach for preparative separation of the instability and bioactive caffeoylquinic acid derivatives from natural products. Full article

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19 pages, 3462 KiB

Open AccessFeature PaperArticle

Inhibition of Cytochrome P450 Activities by Extracts of Hyptis verticillata Jacq.: Assessment for Potential HERB-Drug Interactions

by David Picking¹, Bentley Chambers², James Barker³

, Iltaf Shah⁴

, Roy Porter⁵, Declan P Naughton³ and Rupika Delgoda^1,*

¹ Natural Products Institute, University of the West Indies, Mona, Kingston 7, Jamaica

² Tropical Medicine Research Institute, University of the West Indies, Mona, Kingston 7, Jamaica

³ School of Life Sciences, Pharmacy & Chemistry, Kingston University, Kingston upon Thames, UK

⁴ College of Science, United Arab Emirates University, Al-Ain 009713, United Arab Emirates

⁵ Department of Chemistry, University of the West Indies, Mona, Kingston 7, Jamaica

Molecules 2018, 23(2), 430; https://doi.org/10.3390/molecules23020430 - 15 Feb 2018

Cited by 17 | Viewed by 5353

Abstract

Understanding the potential for adverse drug reactions (ADRs), from herb-drug interactions, is a key aspect of medicinal plant safety, with particular relevance for public health in countries where medicinal plant use is highly prevalent. We undertook an in-depth assessment of extracts of Hyptis [...] Read more.

Understanding the potential for adverse drug reactions (ADRs), from herb-drug interactions, is a key aspect of medicinal plant safety, with particular relevance for public health in countries where medicinal plant use is highly prevalent. We undertook an in-depth assessment of extracts of Hyptis verticillata Jacq., via its impact on activities of key cytochrome P450 (CYP) enzymes (CYPs 1A1, 1A2, 1B1, 3A4 and 2D6), its antioxidant properties (determined by DPPH assays) and chemical characterisation (using LC-MS). The dried plant aqueous extract demonstrated potent inhibition of the activities of CYPs 1A1 (7.6 µg/mL), 1A2 (1.9 µg/mL), 1B1 (9.4 µg/mL) and 3A4 (6.8 µg/mL). Further analysis of other crude extracts demonstrated potent inhibition of CYP1A2 activity for a dried plant ethanol extract (1.5 µg/mL), fresh plant ethanol extract (3.9 µg/mL), and moderate activity for a fresh plant aqueous extract (27.8 µg/mL). All four extracts demonstrated strong antioxidant activity, compared to the positive control (ascorbic acid, 1.3 µg/mL), with the dried plant ethanol extract being the most potent (1.6 µg/mL). Analysis of the dried plant aqueous extract confirmed the identity of seven phytochemicals, five lignans and two triterpenes. Individual screening of these phytochemicals against the activity of CYP1A2 identified yatein as a moderate inhibitor (71.9 μM), likely to contribute to the plant extract’s potent bioactivity. Further analysis on the impact of this plant on key drug metabolizing enzymes in vivo appears warranted for likely ADRs, as well as furthering development as a potential chemopreventive agent. Full article

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14 pages, 1376 KiB

Open AccessFeature PaperArticle

The Lewis Pair Polymerization of Lactones Using Metal Halides and N-Heterocyclic Olefins: Theoretical Insights

by Jan Meisner¹

, Johannes Karwounopoulos¹, Patrick Walther²

, Johannes Kästner¹

and Stefan Naumann^2,*

¹ Institute of Theoretical Chemistry, University of Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart, Germany

² Institute of Polymer Chemistry, University of Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart, Germany

Molecules 2018, 23(2), 432; https://doi.org/10.3390/molecules23020432 - 15 Feb 2018

Cited by 27 | Viewed by 6452

Abstract

Lewis pair polymerization employing N-Heterocyclic olefins (NHOs) and simple metal halides as co-catalysts has emerged as a useful tool to polymerize diverse lactones. To elucidate some of the mechanistic aspects that remain unclear to date and to better understand the impact of [...] Read more.

Lewis pair polymerization employing N-Heterocyclic olefins (NHOs) and simple metal halides as co-catalysts has emerged as a useful tool to polymerize diverse lactones. To elucidate some of the mechanistic aspects that remain unclear to date and to better understand the impact of the metal species, computational methods have been applied. Several key aspects have been considered: (1) the formation of NHO-metal halide adducts has been evaluated for eight different NHOs and three different Lewis acids, (2) the coordination of four lactones to MgCl₂ was studied and (3) the deprotonation of an initiator (butanol) was investigated in the presence and absence of metal halide for one specific Lewis pair. It was found that the propensity for adduct formation can be influenced, perhaps even designed, by varying both organic and metallic components. Apart from the NHO backbone, the substituents on the exocyclic, olefinic carbon have emerged as interesting tuning site. The tendency to form adducts is ZnCl₂ > MgCl₂ > LiCl. If lactones coordinate to MgCl₂, the most likely binding mode is via the carbonyl oxygen. A chelating coordination cannot be ruled out and seems to gain importance upon increasing ring-size of the lactone. For a representative NHO, it is demonstrated that in a metal-free setting an initiating alcohol cannot be deprotonated, while in the presence of MgCl₂ the same process is exothermic with a low barrier. Full article

(This article belongs to the Special Issue Lewis Pair Polymerization for New Reactivity and Structure in Polymer Synthesis)

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12 pages, 6931 KiB

Open AccessArticle

Pd-Catalyzed, Highly Selective C(sp²)-Br Bond Coupling Reactions of o-(or m-, or p-) Chloromethyl Bromobenzene with Arylboronic Acids

by Ming-ming Pei, Ping Liu^*, Yan Liu, Xin-ming Lv, Xiao-wei Ma^* and Bin Dai

School of Chemistry and Chemical Engineering/Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, Shihezi University, Shihezi 832003, China

Molecules 2018, 23(2), 433; https://doi.org/10.3390/molecules23020433 - 15 Feb 2018

Cited by 5 | Viewed by 4601

Abstract

Highly selective C(sp²)–C(sp²) cross-coupling of dihalogenated hydrocarbons comprising C(sp²)–Br and C(sp³)–Cl bonds with arylboronic acids is reported. This highly selective coupling reaction of the C(sp²)–Br bond is successfully achieved using Pd(OAc)₂ and [...] Read more.

Highly selective C(sp²)–C(sp²) cross-coupling of dihalogenated hydrocarbons comprising C(sp²)–Br and C(sp³)–Cl bonds with arylboronic acids is reported. This highly selective coupling reaction of the C(sp²)–Br bond is successfully achieved using Pd(OAc)₂ and PCy₃·HBF₄ as the palladium source and ligand, respectively. A series of chloromethyl-1,1′-biphenyl compounds are obtained in moderate-to-excellent yields. Moreover, this protocol can be extended to the one-pot dual arylation of 1-bromo-4-(chloromethyl)benzene with two arylboronic acids, leading to diverse unsymmetrical 4-benzyl-1,1′-biphenyl derivatives. Full article

(This article belongs to the Special Issue Palladium Catalysts 2018)

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11 pages, 5120 KiB

Open AccessArticle

Design, Synthesis and DFT/DNP Modeling Study of New 2-Amino-5-arylazothiazole Derivatives as Potential Antibacterial Agents

by Sraa Abu-Melha

Department of Chemistry, Faculty of Science of Girls, King Khaled University, Abha 62529, Saudi Arabia

Molecules 2018, 23(2), 434; https://doi.org/10.3390/molecules23020434 - 15 Feb 2018

Cited by 27 | Viewed by 4759

Abstract

A new series of 2-amino-5-arylazothiazole derivatives has been designed and synthesized in 61–78% yields and screened as potential antibacterial drug candidates against the Gram negative bacterium Escherichia coli. The geometry of the title compounds were being studied using the Material Studio package and [...] Read more.

A new series of 2-amino-5-arylazothiazole derivatives has been designed and synthesized in 61–78% yields and screened as potential antibacterial drug candidates against the Gram negative bacterium Escherichia coli. The geometry of the title compounds were being studied using the Material Studio package and semi-core pseudopods calculations (dspp) were performed with the double numerica basis sets plus polarization functional (DNP) to predict the properties of materials using the hybrid FT/B3LYP method. Modeling calculations, especially the (E_H-E_L) difference and the energetic parameters revealed that some of the title compounds may be promising tools for further research work and the activity is structure dependent. Full article

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17 pages, 1779 KiB

Open AccessArticle

Dynamic Changes in Phenolics and Antioxidant Capacity during Pecan (Carya illinoinensis) Kernel Ripening and Its Phenolics Profiles

by Xiaodong Jia^1,2, Huiting Luo², Mengyang Xu², Min Zhai², Zhongren Guo², Yushan Qiao^1,*

and Liangju Wang^1,*

¹ College of Horticulture, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China

² Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, Jiangsu, China

Molecules 2018, 23(2), 435; https://doi.org/10.3390/molecules23020435 - 16 Feb 2018

Cited by 52 | Viewed by 5126

Abstract

Pecan (Carya illinoinensis) kernels have a high phenolics content and a high antioxidant capacity compared to other nuts—traits that have attracted great interest of late. Changes in the total phenolic content (TPC), condensed tannins (CT), total flavonoid content (TFC), five individual [...] Read more.

Pecan (Carya illinoinensis) kernels have a high phenolics content and a high antioxidant capacity compared to other nuts—traits that have attracted great interest of late. Changes in the total phenolic content (TPC), condensed tannins (CT), total flavonoid content (TFC), five individual phenolics, and antioxidant capacity of five pecan cultivars were investigated during the process of kernel ripening. Ultra-performance liquid chromatography coupled with quadruple time-of-flight mass (UPLC-Q/TOF-MS) was also used to analyze the phenolics profiles in mixed pecan kernels. TPC, CT, TFC, individual phenolics, and antioxidant capacity were changed in similar patterns, with values highest at the water or milk stages, lowest at milk or dough stages, and slightly varied at kernel stages. Forty phenolics were tentatively identified in pecan kernels, of which two were first reported in the genus Carya, six were first reported in Carya illinoinensis, and one was first reported in its kernel. The findings on these new phenolic compounds provide proof of the high antioxidant capacity of pecan kernels. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

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18 pages, 3034 KiB

Open AccessFeature PaperArticle

Probing the Influence of Linker Length and Flexibility in the Design and Synthesis of New Trehalase Inhibitors

by Giampiero D’Adamio¹, Matilde Forcella²

, Paola Fusi², Paolo Parenti³

, Camilla Matassini^1,4,*

, Xhenti Ferhati¹, Costanza Vanni¹

and Francesca Cardona^1,4,5,*

¹ Department of Chemistry ‘Ugo Schiff’, University of Florence, via della Lastruccia 3-13, I-50019 Sesto Fiorentino (FI), Italy

² Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy

³ Department of Earth and Environmental Sciences, University of Milano-Bicocca, Piazza della Scienza 1, 20126 Milano, Italy

⁴ Associated with CNR-INO, Via N. Carrara 1, I-50019 Sesto Fiorentino (FI), Italy

⁵ Associated with Consorzio Interuniversitario Nazionale di ricerca in Metodologie e Processi Innovativi di Sintesi (CINMPIS), Università di Bari, 70125 Bari, Italy

Molecules 2018, 23(2), 436; https://doi.org/10.3390/molecules23020436 - 16 Feb 2018

Cited by 11 | Viewed by 4083

Abstract

This work aims to synthesize new trehalase inhibitors selective towards the insect trehalase versus the porcine trehalase, in view of their application as potentially non-toxic insecticides and fungicides. The synthesis of a new pseudodisaccharide mimetic 8, by means of a stereoselective α-glucosylation [...] Read more.

This work aims to synthesize new trehalase inhibitors selective towards the insect trehalase versus the porcine trehalase, in view of their application as potentially non-toxic insecticides and fungicides. The synthesis of a new pseudodisaccharide mimetic 8, by means of a stereoselective α-glucosylation of the key pyrrolizidine intermediate 13, was accomplished. The activity of compound 8 as trehalase inhibitor towards C. riparius trehalase was evaluated and the results showed that 8 was active in the μM range and showed a good selectivity towards the insect trehalase. To reduce the overall number of synthetic steps, simpler and more flexible disaccharide mimetics 9–11 bearing a pyrrolidine nucleus instead of the pyrrolizidine core were synthesized. The biological data showed the key role of the linker chain’s length in inducing inhibitory properties, since only compounds 9 (α,β-mixture), bearing a two-carbon atom linker chain, maintained activity as trehalase inhibitors. A proper change in the glucosyl donor-protecting groups allowed the stereoselective synthesis of the β-glucoside 9β, which was active in the low micromolar range (IC₅₀ = 0.78 μM) and 12-fold more potent (and more selective) than 9α towards the insect trehalase. Full article

(This article belongs to the Special Issue Glycomimetics: Design, Synthesis and Therapeutic Applications)

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15 pages, 5642 KiB

Open AccessArticle

Complete Chloroplast Genomes of Papaver rhoeas and Papaver orientale: Molecular Structures, Comparative Analysis, and Phylogenetic Analysis

by Jianguo Zhou¹, Yingxian Cui¹, Xinlian Chen¹, Ying Li¹, Zhichao Xu¹, Baozhong Duan², Yonghua Li³, Jingyuan Song¹ and Hui Yao^1,*

¹ Key Lab of Chinese Medicine Resources Conservation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China

² College of Pharmaceutical Science, Dali University, Dali 671000, China

³ Department of Pharmacy, Guangxi Traditional Chinese Medicine University, Nanning 530200, China

Molecules 2018, 23(2), 437; https://doi.org/10.3390/molecules23020437 - 16 Feb 2018

Cited by 69 | Viewed by 6897

Abstract

Papaver rhoeas L. and P. orientale L., which belong to the family Papaveraceae, are used as ornamental and medicinal plants. The chloroplast genome has been used for molecular markers, evolutionary biology, and barcoding identification. In this study, the complete chloroplast genome sequences of [...] Read more.

Papaver rhoeas L. and P. orientale L., which belong to the family Papaveraceae, are used as ornamental and medicinal plants. The chloroplast genome has been used for molecular markers, evolutionary biology, and barcoding identification. In this study, the complete chloroplast genome sequences of P. rhoeas and P. orientale are reported. Results show that the complete chloroplast genomes of P. rhoeas and P. orientale have typical quadripartite structures, which are comprised of circular 152,905 and 152,799-bp-long molecules, respectively. A total of 130 genes were identified in each genome, including 85 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Sequence divergence analysis of four species from Papaveraceae indicated that the most divergent regions are found in the non-coding spacers with minimal differences among three Papaver species. These differences include the ycf1 gene and intergenic regions, such as rpoB-trnC, trnD-trnT, petA-psbJ, psbE-petL, and ccsA-ndhD. These regions are hypervariable regions, which can be used as specific DNA barcodes. This finding suggested that the chloroplast genome could be used as a powerful tool to resolve the phylogenetic positions and relationships of Papaveraceae. These results offer valuable information for future research in the identification of Papaver species and will benefit further investigations of these species. Full article

(This article belongs to the Section Molecular Diversity)

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18 pages, 3032 KiB

Open AccessArticle

Asymmetric Synthesis of Spirooxindoles via Nucleophilic Epoxidation Promoted by Bifunctional Organocatalysts

by Martina Miceli¹

, Andrea Mazziotta¹, Chiara Palumbo¹, Elia Roma¹

, Eleonora Tosi¹, Giovanna Longhi²

, Sergio Abbate², Paolo Lupattelli³

, Giuseppe Mazzeo²

and Tecla Gasperi^1,*

¹ Dipartimento di Scienze- Sezione di Nanoscienze e Nanotecnologie, Università degli Studi di Roma Tre, V.le G. Marconi 446, I-00146 Rome, Italy

² Dipartimento di Medicina Molecolare e Traslazionale (DMMT), Università di Brescia, viale Europa 11, 25123 Brescia, Italy

³ Dipartimento di Scienze, Università degli Studi della Basilicata, via dell′Ateneo Lucano 10, I-85100 Potenza, Italy

Molecules 2018, 23(2), 438; https://doi.org/10.3390/molecules23020438 - 16 Feb 2018

Cited by 6 | Viewed by 3515

Abstract

Taking into account the postulated reaction mechanism for the organocatalytic epoxidation of electron-poor olefins developed by our laboratory, we have investigated the key factors able to positively influence the H-bond network installed inside the substrate/catalyst/oxidizing agent. With this aim, we have: (i) tested [...] Read more.

Taking into account the postulated reaction mechanism for the organocatalytic epoxidation of electron-poor olefins developed by our laboratory, we have investigated the key factors able to positively influence the H-bond network installed inside the substrate/catalyst/oxidizing agent. With this aim, we have: (i) tested a few catalysts displaying various effects that noticeably differ in terms of steric hindrance and electron demand; (ii) employed α-alkylidene oxindoles decorated with different substituents on the aromatic ring (11a–g), the exocylic double bond (11h–l), and the amide moiety (11m–v). The observed results suggest that the modification of the electron-withdrawing group (EWG) weakly conditions the overall outcomes, and conversely a strong influence is unambiguously ascribable to either the N-protected or N-unprotected lactam framework. Specifically, when the NH free substrates (11m–u) are employed, an inversion of the stereochemical control is observed, while the introduction of a Boc protecting group affords the desired product 12v in excellent enantioselectivity (97:3 er). Full article

(This article belongs to the Special Issue Enantioselective Catalysis)

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10 pages, 630 KiB

Open AccessArticle

Preparation of Novel Homodimers Derived from Cytotoxic Isoquinolinequinones. A Twin Drug Approach

by Juana Andrea Ibacache^1,*, Judith Faundes¹, Margarita Montoya¹, Sophia Mejías¹ and Jaime A. Valderrama^2,*

¹ Facultad de Química y Biología, Universidad de Santiago de Chile, Alameda 3363, Casilla 40, Santiago 9170022, Chile

² Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile

Molecules 2018, 23(2), 439; https://doi.org/10.3390/molecules23020439 - 16 Feb 2018

Cited by 17 | Viewed by 3243

Abstract

The synthesis of five novel homodimers is reported based on the anilinoisoquinolinequinone scaffold. In these twin-drug derivatives, two units of the anilinoquinone pharmacophores are linked through a methylene spacer. The formation of dimers was achieved by reaction of isoquinolinequinones with 4, 4’-diaminodiphenylmethane via [...] Read more.

The synthesis of five novel homodimers is reported based on the anilinoisoquinolinequinone scaffold. In these twin-drug derivatives, two units of the anilinoquinone pharmacophores are linked through a methylene spacer. The formation of dimers was achieved by reaction of isoquinolinequinones with 4, 4’-diaminodiphenylmethane via a sequence of two oxidative amination reactions. A preliminary in vitro screening of the homodimers reveals moderate to high cytotoxic activities against MDA-MB-21 breast adenocarcinoma and B16-F10 murine metastatic melanoma cell lines. The asymmetrical homodimer 15 stands out due to its cytotoxic potencies at submicromolar concentrations and high selectivity index (mean IC₅₀ = 0.37 μM; SI = 6.97) compared to those of etoposide (mean IC₅₀ = 3.67; SI = 0.32) and taxol (mean IC₅₀ = 0.35; SI = 0.91) employed as reference anticancer drugs. Full article

(This article belongs to the Section Organic Chemistry)

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23 pages, 1537 KiB

Open AccessFeature PaperArticle

Ionic Liquid-Promoted Synthesis of Novel Chromone-Pyrimidine Coupled Derivatives, Antimicrobial Analysis, Enzyme Assay, Docking Study and Toxicity Study

by Shailee V. Tiwari¹, Julio A. Seijas²

, Maria Pilar Vazquez-Tato², Aniket P. Sarkate³, Kshipra S. Karnik³ and Anna Pratima G. Nikalje^1,*

¹ Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Rauza Baug, Aurangabad, Maharashtra 431001, India

² Departamento de Química Orgánica, Facultad de Ciencias, Universidad of Santiago De Compostela, Alfonso X el Sabio, 27002 Lugo, Spain

³ Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra 431004, India

Molecules 2018, 23(2), 440; https://doi.org/10.3390/molecules23020440 - 16 Feb 2018

Cited by 31 | Viewed by 4522

Abstract

Herein, we report an environmentally friendly, rapid, and convenient ionic liquid ([Et₃NH][HSO₄])-promoted facile synthesis of ethyl 4-(6-substituted-4-oxo-4H-chromen-3-yl)-6-methyl-2-thioxo/oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives 4(a–f) and 4-(6-substituted-4-oxo-4H-chromen-3-yl)-6-methyl-2-thioxo/oxo-1,2,3,4-tetrahydropyrimidine-5- carbohydrazide derivatives 6(a–f). All the synthesized derivatives 4 [...] Read more.

Herein, we report an environmentally friendly, rapid, and convenient ionic liquid ([Et₃NH][HSO₄])-promoted facile synthesis of ethyl 4-(6-substituted-4-oxo-4H-chromen-3-yl)-6-methyl-2-thioxo/oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives 4(a–f) and 4-(6-substituted-4-oxo-4H-chromen-3-yl)-6-methyl-2-thioxo/oxo-1,2,3,4-tetrahydropyrimidine-5- carbohydrazide derivatives 6(a–f). All the synthesized derivatives 4(a–f) and 6(a–f) were evaluated for their in vitro antifungal and antibacterial activity, by method recommended by National Committee for Clinical Laboratory Standards (NCCLS). The compound 6c bearing a fluoro group on the chromone ring and oxygen and a hydrazino group (–NHNH₂) on the pyrimidine ring, was found to be the most potent antibacterial compound amongst the synthesized derivatives. The compound 6f bearing a methoxy group (–OCH₃) on the chromone ring and sulphur group on the pyrimidine ring, was found to exhibit equipotent antifungal activity when compared with the standard drug miconazole. A d-alanine-d-alanine ligase (DdlB) enzyme assay study and an ergosterol extraction and quantitation assay study were performed to predict the mode of action of the synthesized compounds. A molecular docking study was performed to predict the binding interactions with receptors and mode of action of the synthesized derivatives. Further, analysis of the ADMET parameters for the synthesized compounds has shown that these compounds have good oral drug-like properties and can be developed as oral drug candidates. To establish the antimicrobial selectivity and safety, the most active compounds 6c and 6f were further tested for cytotoxicity against the human cancer cell line HeLa and were found to be non-cytotoxic in nature. An in vivo acute oral toxicity study was also performed for the most active compounds 6c and 6f and the results indicated that the compounds are non-toxic in nature. Full article

(This article belongs to the Special Issue ECSOC-21)

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18 pages, 2244 KiB

Open AccessFeature PaperArticle

Liposomal Formulations for an Efficient Encapsulation of Epigallocatechin-3-Gallate: An In-Silico/Experimental Approach

by Emiliano Laudadio¹

, Cristina Minnelli¹, Adolfo Amici²

, Luca Massaccesi¹, Giovanna Mobbili^1,* and Roberta Galeazzi^1,*

¹ Dipartimento di Scienze della Vita e dell’Ambiente (DISVA), Università Politecnica delle Marche, via Brecce Bianche, 60131 Ancona, Italy

² Dipartimento Scienze Cliniche Specialistiche ed Odontostomatologiche, Università Politecnica delle Marche, via Brecce Bianche, 60131 Ancona, Italy

Molecules 2018, 23(2), 441; https://doi.org/10.3390/molecules23020441 - 16 Feb 2018

Cited by 23 | Viewed by 4389

Abstract

As a part of research project aimed to optimize antioxidant delivery, here we studied the influence of both salts and lipid matrix composition on the interaction of epigallocatechin-3-gallate (EGCG) with bilayer leaflets. Thus, we combined in silico and experimental methods to study the [...] Read more.

As a part of research project aimed to optimize antioxidant delivery, here we studied the influence of both salts and lipid matrix composition on the interaction of epigallocatechin-3-gallate (EGCG) with bilayer leaflets. Thus, we combined in silico and experimental methods to study the ability of neutral and anionic vesicles to encapsulate EGCG in the presence of Ca²⁺ and Mg²⁺ divalent salts. Experimental and in silico results show a very high correlation, thus confirming the efficiency of the developed methodology. In particular, we found out that the presence of calcium ions hinders the insertion of EGCG in the liposome bilayer in both neutral and anionic systems. On the contrary, the presence of MgCl₂ improves the insertion degree of EGCG molecules respect to the liposomes without divalent salts. The best and most efficient salt concentration is that corresponding to a 5:1 molar ratio between Mg²⁺ and EGCG, in both neutral and anionic vesicles. Concerning the lipid matrix composition, the anionic one results in better promotion of the catechin insertion within the bilayer since experimentally we achieved 100% EGCG encapsulation in the lipid carrier in the presence of a 5:1 molar ratio of magnesium. Thus, the combination of this anionic liposomal formulation with magnesium chloride, avoids time-consuming separation steps of unentrapped active principle and appears particularly suitable for EGCG delivery applications. Full article

(This article belongs to the Special Issue Liposomes as Drug Carriers)

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11 pages, 1072 KiB

Open AccessFeature PaperArticle

Controlled and Efficient Polymerization of Conjugated Polar Alkenes by Lewis Pairs Based on Sterically Hindered Aryloxide-Substituted Alkylaluminum

by Xiaojun Wang, Yixin Zhang and Miao Hong^*

State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China

Molecules 2018, 23(2), 442; https://doi.org/10.3390/molecules23020442 - 17 Feb 2018

Cited by 19 | Viewed by 5217

Abstract

Reported herein is the development of an effective strategy for controlled and efficient Lewis pair polymerization of conjugated polar alkenes, including methyl methacrylate (MMA), n-butyl methacrylate (ⁿBuMA), and γ-methyl-α-methylene-γ-butyrolactone (γMMBL), by the utilization of sterically encumbered Al(BHT)₂Me (BHT: [...] Read more.

Reported herein is the development of an effective strategy for controlled and efficient Lewis pair polymerization of conjugated polar alkenes, including methyl methacrylate (MMA), n-butyl methacrylate (ⁿBuMA), and γ-methyl-α-methylene-γ-butyrolactone (γMMBL), by the utilization of sterically encumbered Al(BHT)₂Me (BHT: 2,6-di-tert-butyl-4-methylphenol) as a Lewis acid that shuts down intramolecular backbiting termination. In combination with a selected N-heterocyclic carbene (NHC) as a Lewis base, the polymerization of MMA exhibited activity up to 3000 h⁻¹ TOF and an acceptable initiation efficiency of 60.6%, producing polymers with high molecular weight (M_n up to 130 kg/mol) and extremely narrow dispersity (Đ = 1.06~1.13). This controlled polymerization with a living characteristic has been evidenced by chain-extension experiments and chain-end analysis, and enabled the synthesis of well-defined diblock copolymers. Full article

(This article belongs to the Special Issue Lewis Pair Polymerization for New Reactivity and Structure in Polymer Synthesis)

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18 pages, 5280 KiB

Open AccessArticle

Behavior of the E–E’ Bonds (E, E’ = S and Se) in Glutathione Disulfide and Derivatives Elucidated by Quantum Chemical Calculations with the Quantum Theory of Atoms-in-Molecules Approach

by Satoko Hayashi^*, Yutaka Tsubomoto and Waro Nakanishi^*

Faculty of Systems Engineering, Wakayama University, 930 Sakaedani, Wakayama 640-8510, Japan

Molecules 2018, 23(2), 443; https://doi.org/10.3390/molecules23020443 - 17 Feb 2018

Cited by 5 | Viewed by 3351

Abstract

The nature of the E–E’ bonds (E, E’ = S and Se) in glutathione disulfide (1) and derivatives 2–3, respectively, was elucidated by applying quantum theory of atoms-in-molecules (QTAIM) dual functional analysis (QTAIM-DFA), to clarify the basic contribution [...] Read more.

The nature of the E–E’ bonds (E, E’ = S and Se) in glutathione disulfide (1) and derivatives 2–3, respectively, was elucidated by applying quantum theory of atoms-in-molecules (QTAIM) dual functional analysis (QTAIM-DFA), to clarify the basic contribution of E–E’ in the biological redox process, such as the glutathione peroxidase process. Five most stable conformers a–e were obtained, after applying the Monte-Carlo method then structural optimizations. In QTAIM-DFA, total electron energy densities H_b(r_c) are plotted versus H_b(r_c) − V_b(r_c)/2 at bond critical points (BCPs), where V_b(r_c) are potential energy densities at BCPs. Data from the fully optimized structures correspond to the static nature. Those containing perturbed structures around the fully optimized one in the plot represent the dynamic nature of interactions. The behavior of E–E’ was examined carefully. Whereas E–E’ in 1a–3e were all predicted to have the weak covalent nature of the shared shell interactions, two different types of S–S were detected in 1, depending on the conformational properties. Contributions from the intramolecular non-covalent interactions to stabilize the conformers were evaluated. An inverse relationship was observed between the stability of a conformer and the strength of E–E’ in the conformer, of which reason was discussed. Full article

(This article belongs to the Section Computational and Theoretical Chemistry)

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21 pages, 4483 KiB

Open AccessArticle

Overexpression of Receptor Tyrosine Kinase EphB4 Triggers Tumor Growth and Hypoxia in A375 Melanoma Xenografts: Insights from Multitracer Small Animal Imaging Experiments

by Christin Neuber¹, Birgit Belter^1,‡, Sebastian Meister^1,‡, Frank Hofheinz^2,‡

, Ralf Bergmann¹, Hans-Jürgen Pietzsch³ and Jens Pietzsch^1,4,*

¹ Department Radiopharmaceutical and Chemical Biology, Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstrasse 400, 01314 Dresden, Germany

² Department Positron Emission Tomography, Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstrasse 400, 01314 Dresden, Germany

³ Department Radionuclide Theragnostics, Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstrasse 400, 01314 Dresden, Germany

⁴ Faculty of Chemistry and Food Chemistry, School of Science, Technische Universität Dresden, 01062 Dresden, Germany

^‡ These authors contributed equally to this work.

Molecules 2018, 23(2), 444; https://doi.org/10.3390/molecules23020444 - 17 Feb 2018

Cited by 11 | Viewed by 5285

Abstract

Experimental evidence has associated receptor tyrosine kinase EphB4 with tumor angiogenesis also in malignant melanoma. Considering the limited in vivo data available, we have conducted a systematic multitracer and multimodal imaging investigation in EphB4-overexpressing and mock-transfected A375 melanoma xenografts. Tumor growth, perfusion, and [...] Read more.

Experimental evidence has associated receptor tyrosine kinase EphB4 with tumor angiogenesis also in malignant melanoma. Considering the limited in vivo data available, we have conducted a systematic multitracer and multimodal imaging investigation in EphB4-overexpressing and mock-transfected A375 melanoma xenografts. Tumor growth, perfusion, and hypoxia were investigated by positron emission tomography. Vascularization was investigated by fluorescence imaging in vivo and ex vivo. The approach was completed by magnetic resonance imaging, radioluminography ex vivo, and immunohistochemical staining for blood and lymph vessel markers. Results revealed EphB4 to be a positive regulator of A375 melanoma growth, but a negative regulator of tumor vascularization. Resulting in increased hypoxia, this physiological characteristic is considered as highly unfavorable for melanoma prognosis and therapy outcome. Lymphangiogenesis, by contrast, was not influenced by EphB4 overexpression. In order to distinguish between EphB4 forward and EphrinB2, the natural EphB4 ligand, reverse signaling a specific EphB4 kinase inhibitor was applied. Blocking experiments show EphrinB2 reverse signaling rather than EphB4 forward signaling to be responsible for the observed effects. In conclusion, functional expression of EphB4 is considered a promising differentiating characteristic, preferentially determined by non-invasive in vivo imaging, which may improve personalized theranostics of malignant melanoma. Full article

(This article belongs to the Special Issue Molecular Imaging and Treatment Monitoring of Cancer)

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14 pages, 1644 KiB

Open AccessArticle

Efficiency of Osmotic Dehydration of Apples in Polyols Solutions

by Joanna Cichowska^*, Joanna Żubernik, Jakub Czyżewski, Hanna Kowalska and Dorota Witrowa-Rajchert

Department of Food Engineering and Process Management, Warsaw University of Life Sciences, Nowoursynowska 166, 02-787 Warszawa, Poland

Molecules 2018, 23(2), 446; https://doi.org/10.3390/molecules23020446 - 17 Feb 2018

Cited by 25 | Viewed by 5787

Abstract

The present study aimed to evaluate the influence of selected compounds from the polyol group, as well as other saccharides, on the osmotic dehydration process of apples. The following alternative solutions were examined: erythritol, xylitol, maltitol, inulin and oligofructose. Efficiency of the osmotic [...] Read more.

The present study aimed to evaluate the influence of selected compounds from the polyol group, as well as other saccharides, on the osmotic dehydration process of apples. The following alternative solutions were examined: erythritol, xylitol, maltitol, inulin and oligofructose. Efficiency of the osmotic dehydration process was evaluated based on the kinetics of the process, and through comparison of the results obtained during the application of a sucrose solution. This innovative research utilizes alternative solutions in osmotic pretreatment, which until now, have not been commonly used in fruit processing by researchers worldwide. Results indicate that erythritol and xylitol show stronger or similar efficiency to sucrose; however, the use of inulin, as well as oligofructose, was not satisfactory due to the insufficient, small osmotic driving forces of the process, and the low values of mass transfer parameters. Full article

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14 pages, 3157 KiB

Open AccessArticle

New Bacterial Phytase through Metagenomic Prospection

by Nathálya Farias¹, Isabela Almeida²

and Carlos Meneses^3,*

¹ Graduate Program in Agricultural Sciences, Universidade Estadual da Paraíba (UEPB), Campina Grande/PB 58429-500, Brazil

² Department of Biology, Universidade Estadual da Paraíba (UEPB)

³ Department of Biology and Graduate Program in Agricultural Sciences, Universidade Estadual da Paraíba (UEPB), Campina Grande/PB 58429-500, Brazil

Molecules 2018, 23(2), 448; https://doi.org/10.3390/molecules23020448 - 17 Feb 2018

Cited by 18 | Viewed by 5506

Abstract

Alkaline phytases from uncultured microorganisms, which hydrolyze phytate to less phosphorylated myo-inositols and inorganic phosphate, have great potential as additives in agricultural industry. The development of metagenomics has stemmed from the ineluctable evidence that as-yet-uncultured microorganisms represent the vast majority of organisms in [...] Read more.

Alkaline phytases from uncultured microorganisms, which hydrolyze phytate to less phosphorylated myo-inositols and inorganic phosphate, have great potential as additives in agricultural industry. The development of metagenomics has stemmed from the ineluctable evidence that as-yet-uncultured microorganisms represent the vast majority of organisms in most environments on earth. In this study, a gene encoding a phytase was cloned from red rice crop residues and castor bean cake using a metagenomics strategy. The amino acid identity between this gene and its closest published counterparts is lower than 60%. The phytase was named PhyRC001 and was biochemically characterized. This recombinant protein showed activity on sodium phytate, indicating that PhyRC001 is a hydrolase enzyme. The enzymatic activity was optimal at a pH of 7.0 and at a temperature of 35 °C. β-propeller phytases possess great potential as feed additives because they are the only type of phytase with high activity at neutral pH. Therefore, to explore and exploit the underlying mechanism for β-propeller phytase functions could be of great benefit to biotechnology. Full article

(This article belongs to the Section Molecular Diversity)

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8 pages, 1465 KiB

Open AccessArticle

Electronic Structure of C₆₀/Zinc Phthalocyanine/V₂O₅ Interfaces Studied Using Photoemission Spectroscopy for Organic Photovoltaic Applications

by Chang Jin Lim¹, Min Gyu Park¹, Min Su Kim², Jeong Hwa Han², Soohaeng Cho¹, Mann-Ho Cho², Yeonjin Yi², Hyunbok Lee³ and Sang Wan Cho^1,*

¹ Department of Physics, Yonsei University, 1 Yonseidae-gil, Wonju-si, Gangwon-do 26493, Korea

² Institute of Physics and Applied Physics, Yonsei University, 50 Yonsei-ro, Seodaemun-Gu, Seoul 03722, Korea

³ Department of Physics, Kangwon National University, 1 Gangwondaehak-gil, Chuncheon-si, Gaongwon-do 24341, Korea

Molecules 2018, 23(2), 449; https://doi.org/10.3390/molecules23020449 - 18 Feb 2018

Cited by 14 | Viewed by 5210

Abstract

The interfacial electronic structures of a bilayer of fullerene (C₆₀) and zinc phthalocyanine (ZnPc) grown on vanadium pentoxide (V₂O₅) thin films deposited using radio frequency sputtering under various conditions were studied using X-ray and ultraviolet photoelectron spectroscopy. [...] Read more.

The interfacial electronic structures of a bilayer of fullerene (C₆₀) and zinc phthalocyanine (ZnPc) grown on vanadium pentoxide (V₂O₅) thin films deposited using radio frequency sputtering under various conditions were studied using X-ray and ultraviolet photoelectron spectroscopy. The energy difference between the highest occupied molecular orbital (HOMO) level of the ZnPc layer and the lowest unoccupied molecular orbital (LUMO) level of the C₆₀ layer was determined and compared with that grown on an indium tin oxide (ITO) substrate. The energy difference of a heterojunction on all V₂O₅ was found to be 1.3~1.4 eV, while that on ITO was 1.1 eV. This difference could be due to the higher binding energy of the HOMO of ZnPc on V₂O₅ than that on ITO regardless of work functions of the substrates. We also determined the complete energy level diagrams of C₆₀/ZnPc on V₂O₅ and ITO. Full article

(This article belongs to the Special Issue Advanced Functional Dyes)

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12 pages, 1983 KiB

Open AccessArticle

Inhibitory Activity of Allergic Contact Dermatitis and Atopic Dermatitis-Like Skin in BALB/c Mouse through Oral Administration of Fermented Barks of Alnus sibirica

by Jun Yin, Seong Hye Yoon, Hye Shin Ahn and Min Won Lee^*

Laboratory of Pharmacognosy and Natural Product based Medicine, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea

Molecules 2018, 23(2), 450; https://doi.org/10.3390/molecules23020450 - 18 Feb 2018

Cited by 13 | Viewed by 4199

Abstract

Phytochemical isolation of fermented Alnus sibirica (FAS) which was produced by using Lactobacillus plantarum subsp. argentoratensis, exhibited multiple and different composition compared with the original plant. Anti-allergic contact dermatitis (anti-ACD)/anti-atopic dermatitis (anti-AD) activities (visual observation and regulation of Th₁/Th₂ [...] Read more.

Phytochemical isolation of fermented Alnus sibirica (FAS) which was produced by using Lactobacillus plantarum subsp. argentoratensis, exhibited multiple and different composition compared with the original plant. Anti-allergic contact dermatitis (anti-ACD)/anti-atopic dermatitis (anti-AD) activities (visual observation and regulation of Th₁/Th₂ cytokines and IgE in blood) of FAS and the barks of Alnus sibirica extract (AS) and the two diarylheptanoids, hirsutenone (1) and muricarpon B (2), which are major components of FAS, were measured in vitro and in vivo. FAS, AS and the two compounds showed potent anti-oxidative, anti-inflammatory, anti-ACD and anti-AD activity. In particular, FAS showed more potent biological activity than AS. Thus, fermentation might be a prominent way to enhance the biological activity compared with the original plant. In addition, compounds (1) and (2) might be developed as functional materials or herbal medicines for ACD and AD. Full article

(This article belongs to the Section Natural Products Chemistry)

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17 pages, 1913 KiB

Open AccessArticle

Docosahexaenoic Acid Helps to Lessen Extinction Memory in Rats

by Michio Hashimoto^1,*, Shahdat Hossain^1,2, Masanori Katakura¹, Abdullah Al Mamun¹ and Osamu Shido¹

¹ Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan

² Department of Biochemistry & Molecular Biology, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh

Molecules 2018, 23(2), 451; https://doi.org/10.3390/molecules23020451 - 18 Feb 2018

Cited by 8 | Viewed by 3649

Abstract

Abstract: Memory extinction is referred to as a learning process in which a conditioned response (CR) progressively reduces over time as an animal learns to uncouple a response from a stimulus. Extinction occurs when the rat is placed into a context without [...] Read more.

Abstract: Memory extinction is referred to as a learning process in which a conditioned response (CR) progressively reduces over time as an animal learns to uncouple a response from a stimulus. Extinction occurs when the rat is placed into a context without shock after training. Docosahexaenoic acid (DHA, C22:6, n-3) is implicated in memory formation in mammalian brains. In a two-way active shuttle-avoidance apparatus, we examined whether DHA affects the extinction memory and the expression of brain cognition-related proteins, including gastrin-releasing peptide receptor (GRPR), brain-derived neurotrophic factor receptor (BDNFR) tyrosine kinase receptor B (TrKB), and N-methyl-d-aspartate receptor (NMDAR) subunits NR2A and NR2B. Also, the protein levels of GRP, BDNF, postsynaptic density protein-95 (PSD-95), and vesicular acetylcholine transporter (VAChT), and the antioxidative potentials, in terms of lipid peroxide (LPO) and reactive oxygen species (ROS), were examined in the hippocampus. During the acquisition phase, the rats received a conditioned stimulus (CS-tone) paired with an unconditioned stimulus (UCS foot shock) for three consecutive days (Sessions S1, S2, and S3, each consisting of 30-trials) after 12 weeks of oral administration of DHA. After a three-day interval, the rats were re-subjected to two extinction sessions (S4, S5), each comprising 30 trials of CS alone. During the acquisition training in S1, the shock-related avoidance frequency (acquisition memory) was significantly higher in the DHA-administered rats compared with the control rats. The avoidance frequency, however, decreased with successive acquisition trainings in sessions S2 and S3. When the rats were subjected to the extinction sessions after a break for consolidation, the conditioned response (CR) was also significantly higher in the DHA-administered rats. Interestingly, the freezing responses (frequency and time) also significantly decreased in the DHA-administered rats, thus suggesting that a higher coping capacity was present during fear stress in the DHA-administered rats. DHA treatments increased the mRNA levels of GRPR, BDNF receptor TrKB, and NMDAR subunit NR2B. DHA also increased the protein levels of GRP, BDNF, PSD-95, and VAChT, and the antioxidative potentials in the hippocampus. These results suggest the usefulness of DHA for treating stress disorders. Full article

(This article belongs to the Special Issue Neuroprotective Agents)

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25 pages, 4806 KiB

Open AccessArticle

Identification of Novel Protein Kinase Receptor Type 2 Inhibitors Using Pharmacophore and Structure-Based Virtual Screening

by Josiane V. Cruz^1,2,*, Moysés F. A. Neto³, Luciane B. Silva², Ryan Da S. Ramos²

, Josivan Da S. Costa²

, Davi S. B. Brasil⁴, Cleison C. Lobato², Glauber V. Da Costa²

, José Adolfo H. M. Bittencourt², Carlos H. T. P. Da Silva⁵, Franco H. A. Leite³ and Cleydson B. R. Santos^1,2,*

¹ Postgraduate Program in Pharmaceutical Sciences, Federal University of Amapá, Macapá, Amapá 68902-280, Brazil

² Laboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá, Amapá 68902-280, Brazil

³ Laboratory Molecular Modeling, Estadual University of Feira de Santana, Bahia 44036-900, Brazil

⁴ Institute of Technology, Federal University of Pará, Pará, Amazon, Belém 66075-900, Brazil

⁵ Laboratory of Computational Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo 14040-020, Brazil

Molecules 2018, 23(2), 453; https://doi.org/10.3390/molecules23020453 - 18 Feb 2018

Cited by 30 | Viewed by 5906

Abstract

The Protein Kinase Receptor type 2 (RIPK2) plays an important role in the pathogenesis of inflammatory diseases; it signals downstream of the NOD1 and NOD2 intracellular sensors and promotes a productive inflammatory response. However, excessive NOD2 signaling has been associated with various diseases, [...] Read more.

The Protein Kinase Receptor type 2 (RIPK2) plays an important role in the pathogenesis of inflammatory diseases; it signals downstream of the NOD1 and NOD2 intracellular sensors and promotes a productive inflammatory response. However, excessive NOD2 signaling has been associated with various diseases, including sarcoidosis and inflammatory arthritis; the pharmacological inhibition of RIPK2 is an affinity strategy that demonstrates an increased expression of pro-inflammatory secretion activity. In this study, a pharmacophoric model based on the crystallographic pose of ponatinib, a potent RIPK2 inhibitor, and 30 other ones selected from the BindingDB repository database, was built. Compounds were selected based on the available ZINC compounds database and in silico predictions of their pharmacokinetic, toxicity and potential biological activity. Molecular docking was performed to identify the probable interactions of the compounds as well as their binding affinity with RIPK2. The compounds were analyzed to ponatinib and WEHI-345, which also used as a control. At least one of the compounds exhibited suitable pharmacokinetic properties, low toxicity and an interesting binding affinity and high fitness compared with the crystallographic pose of WEHI-345 in complex with RIPK2. This compound also possessed suitable synthetic accessibility, rendering it a potential and very promising RIPK2 inhibitor to be further investigated in regards to different diseases, particularly inflammatory ones. Full article

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13 pages, 1957 KiB

Open AccessArticle

Comparative Transcriptome Analysis Identifies Putative Genes Involved in Dioscin Biosynthesis in Dioscorea zingiberensis

by Jia Li¹, Qin Liang^1,2

, Changfu Li¹, Mengdi Liu^1,2 and Yansheng Zhang^1,*

¹ CAS Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan 430074, China

² College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China

Molecules 2018, 23(2), 454; https://doi.org/10.3390/molecules23020454 - 18 Feb 2018

Cited by 29 | Viewed by 4875

Abstract

Dioscorea zingiberensis is a perennial herb native to China. The rhizome of D. zingiberensis has long been used as a traditional Chinese medicine to treat rheumatic arthritis. Dioscin is the major bioactive ingredient conferring the medicinal property described in Chinese pharmacopoeia. Several previous [...] Read more.

Dioscorea zingiberensis is a perennial herb native to China. The rhizome of D. zingiberensis has long been used as a traditional Chinese medicine to treat rheumatic arthritis. Dioscin is the major bioactive ingredient conferring the medicinal property described in Chinese pharmacopoeia. Several previous studies have suggested cholesterol as the intermediate to the biosynthesis of dioscin, however, the biosynthetic steps to dioscin after cholesterol remain unknown. In this study, a comprehensive D. zingiberensis transcriptome derived from its leaf and rhizome was constructed. Based on the annotation using various public databases, all possible enzymes in the biosynthetic steps to cholesterol were identified. In the late steps beyond cholesterol, cholesterol undergoes site-specific oxidation by cytochrome P450s (CYPs) and glycosylation by UDP-glycosyltransferases (UGTs) to yield dioscin. From the D. zingiberensis transcriptome, a total of 485 unigenes were annotated as CYPs and 195 unigenes with a sequence length above 1000 bp were annotated as UGTs. Transcriptomic comparison revealed 165 CYP annotated unigenes correlating to dioscin biosynthesis in the plant. Further phylogenetic analysis suggested that among those CYP candidates four of them would be the most likely candidates involved in the biosynthetic steps from cholesterol to dioscin. Additionally, from the UGT annotated unigenes, six of them were annotated as 3-O-UGTs and two of them were annotated as rhamnosyltransferases, which consisted of potential UGT candidates involved in dioscin biosynthesis. To further explore the function of the UGT candidates, two 3-O-UGT candidates, named Dz3GT1 and Dz3GT2, were cloned and functionally characterized. Both Dz3GT1 and Dz3GT2 were able to catalyze a C3-glucosylation activity on diosgenin. In conclusion, this study will facilitate our understanding of dioscin biosynthesis pathway and provides a basis for further mining the genes involved in dioscin biosynthesis. Full article

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13 pages, 3571 KiB

Open AccessArticle

Inhibitory Influence of Panax notoginseng Saponins on Aspirin Hydrolysis in Human Intestinal Caco-2 Cells

by Zongxi Sun

, Yali Wu, Bing Yang, Baochen Zhu, Shaonan Hu, Yang Lu^*, Bo Zhao and Shouying Du^*

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China

Molecules 2018, 23(2), 455; https://doi.org/10.3390/molecules23020455 - 18 Feb 2018

Cited by 15 | Viewed by 5301

Abstract

Herb-drug interactions are important safety concerns in clinical practice. The interactions occur firstly in the intestinal absorption for orally administered drugs. Aspirin and Panax notoginseng saponins (PNS)-based drugs are often combined in China to prevent larger-artery atherosclerosis. Here, we aimed to characterize the [...] Read more.

Herb-drug interactions are important safety concerns in clinical practice. The interactions occur firstly in the intestinal absorption for orally administered drugs. Aspirin and Panax notoginseng saponins (PNS)-based drugs are often combined in China to prevent larger-artery atherosclerosis. Here, we aimed to characterize the aspirin transport across Caco-2 cell monolayers, a model of the intestinal absorption, and further to evaluate the influence of PNS on aspirin hydrolysis and the relating mechanisms. Transcellular transport of aspirin and the influence of PNS were explored using Caco-2 cell monolayers. The protein expression of human carboxylesterase 1 (hCE1) and hCE2 in Caco-2 cells after PNS treatment was analyzed by ELISA, and the mRNA level were determined by qRT-PCR. In the study, Caco-2 cells showed high level of hydrolase activity, and most aspirin was hydrolyzed inside the cells during the transport process. Interestingly, PNS were demonstrated to inhibit the esterase activities responsible for aspirin hydrolysis in Caco-2 cells. PNS could also decrease the protein expression of hCE1 and hCE2, whereas exhibited minor effect on the mRNA expression. These results indicated that oral administration of PNS-based drugs might inhibit the hydrolysis of aspirin during intestinal absorption thus promoting its bioavailability. Full article

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19 pages, 7873 KiB

Open AccessArticle

Structural Insights into σ₁ Receptor Interactions with Opioid Ligands by Molecular Dynamics Simulations

by Mateusz Kurciński^1,*, Małgorzata Jarończyk², Piotr F. J. Lipiński³, Jan Cz. Dobrowolski² and Joanna Sadlej^2,4,*

¹ Faculty of Chemistry, University of Warsaw, Pasteur Str.1, 02-093 Warsaw, Poland

² National Medicines Institute, 30/34 Chełmska Str., 00-725 Warsaw, Poland

³ Department of Neuropeptides, Mossakowski Medical Research Center, Polish Academy of Sciences, 02-106 Warsaw, Poland

⁴ Faculty of Mathematics and Natural Sciences. Cardinal Stefan Wyszyński University,1/3 Wóycickiego Str.,01-938 Warsaw, Poland

Molecules 2018, 23(2), 456; https://doi.org/10.3390/molecules23020456 - 18 Feb 2018

Cited by 3 | Viewed by 3679

Abstract

Despite considerable advances over the past years in understanding the mechanisms of action and the role of the σ₁ receptor, several questions regarding this receptor remain unanswered. This receptor has been identified as a useful target for the treatment of a diverse [...] Read more.

Despite considerable advances over the past years in understanding the mechanisms of action and the role of the σ₁ receptor, several questions regarding this receptor remain unanswered. This receptor has been identified as a useful target for the treatment of a diverse range of diseases, from various central nervous system disorders to cancer. The recently solved issue of the crystal structure of the σ₁ receptor has made elucidating the structure–activity relationship feasible. The interaction of seven representative opioid ligands with the crystal structure of the σ₁ receptor (PDB ID: 5HK1) was simulated for the first time using molecular dynamics (MD). Analysis of the MD trajectories has provided the receptor–ligand interaction fingerprints, combining information on the crucial receptor residues and frequency of the residue–ligand contacts. The contact frequencies and the contact maps suggest that for all studied ligands, the hydrophilic (hydrogen bonding) interactions with Glu172 are an important factor for the ligands’ affinities toward the σ₁ receptor. However, the hydrophobic interactions with Tyr120, Val162, Leu105, and Ile124 also significantly contribute to the ligand–receptor interplay and, in particular, differentiate the action of the agonistic morphine from the antagonistic haloperidol. Full article

(This article belongs to the Section Medicinal Chemistry)

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10 pages, 1335 KiB

Open AccessArticle

Antioxidant and Anti-Osteoporosis Activities of Chemical Constituents of the Stems of Zanthoxylum piperitum

by Seo Young Yang¹, Sang-Hyun Lee², Bui Huu Tai³, Hae-Dong Jang² and Young Ho Kim^1,*

¹ College of Pharmacy, Chungnam National University, Daejeon 34134, Korea

² Department of Food and Nutrition, Hannam University, Daejeon 34054, Korea

³ Institute of Marine Biochemistry (IMBC), Vietnam Academy of Science and Technology (VAST), Hanoi 10000, Vietnam

Molecules 2018, 23(2), 457; https://doi.org/10.3390/molecules23020457 - 18 Feb 2018

Cited by 16 | Viewed by 4073

Abstract

Two new lignans, zanthoxyloside C (1) and zanthoxyloside D (2), together with nine known compounds comprising lignans (3–5), flavonoids (6–8), and phenolics (9–11), were isolated from the [...] Read more.

Two new lignans, zanthoxyloside C (1) and zanthoxyloside D (2), together with nine known compounds comprising lignans (3–5), flavonoids (6–8), and phenolics (9–11), were isolated from the methanol extract of the stems of Zanthoxylum piperitum. All isolates were evaluated for their antioxidant and anti-osteoporotic activities using oxygen radical absorbance capacity (ORAC), cupric reducing antioxidant capacity (CUPRAC), and tartrate-resistant acid phosphatase (TRAP) assays. Compounds 7–10 showed peroxyl radical-scavenging capacities and 4, 6–7, and 9 showed reducing capacities. Moreover, compounds 3, 6–9, and 11 significantly suppressed TRAP activities. These results indicated that the stems of Z. piperitum could be an excellent source for natural antioxidant and anti-osteoporosis. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 6224 KiB

Open AccessArticle

Trifluoromethyl Boron Dipyrromethene Derivatives as Potential Photosensitizers for Photodynamic Therapy

by Jian-Yong Liu^*, Peng-Zhen Zhou, Jia-Lin Ma and Xiao Jia

State Key Laboratory of Photocatalysis on Energy and Environment & National & Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, College of Chemistry, Fuzhou University, Fuzhou 350108, China

Molecules 2018, 23(2), 458; https://doi.org/10.3390/molecules23020458 - 19 Feb 2018

Cited by 15 | Viewed by 3610

Abstract

In this study, two novel boron dipyrromethene-based photosensitizers (BDP3and BDP6) substituted with three or six trifluoromethyl groups have been synthesized and characterized with various spectroscopic methods, and their photo-physical, photo-chemical, and photo-biological properties have also been explored. The two photosensitizers [...] Read more.

In this study, two novel boron dipyrromethene-based photosensitizers (BDP3and BDP6) substituted with three or six trifluoromethyl groups have been synthesized and characterized with various spectroscopic methods, and their photo-physical, photo-chemical, and photo-biological properties have also been explored. The two photosensitizers are highly soluble and remain nonaggregated in N,N-dimethylformamide as shown by the intense and sharp Q-band absorption. Under red light irradiation (λ = 660 nm, 1.5 J/cm²), both photosensitizers show high and comparable cytotoxicity towards HepG2 human hepatocarcinoma and HeLa human cervical carcinoma cells with IC₅₀ values of 0.42–0.49 μM. The high photocytotoxicity of BDP3and BDP6 can be due to their high cellular uptake and low aggregation tendency in biological media, which result in a high efficiency to generate reactive oxygen species inside the cells. Confocal laser fluorescence microscopic studies indicate that they have superior selective affinities to the mitochondria and lysosomes of HepG2 and HeLa cells. The results show that these two trifluoromethyl boron dipyrromethene derivatives are potential anticancer agents for photodynamic therapy. Full article

(This article belongs to the Section Photochemistry)

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17 pages, 671 KiB

Open AccessArticle

Nutritional Composition and Antioxidant Properties of the Fruits of a Chinese Wild Passiflora foetida

by Ya Song¹, Xiao-Qun Wei¹, Mei-Ying Li¹, Xue-Wu Duan², Yuan-Ming Sun¹, Rui-Li Yang¹, Xiang-Dong Su³, Ri-Ming Huang^1,* and Hong Wang^1,*

¹ Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou 510642, China

² Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, China

³ Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK

Molecules 2018, 23(2), 459; https://doi.org/10.3390/molecules23020459 - 19 Feb 2018

Cited by 27 | Viewed by 5813

Abstract

The aim of this work was to evaluate the main nutrients and their antioxidant properties of a Chinese wild edible fruit, Passiflora foetida, collected from the ecoregion of Hainan province, China. The analytical results revealed that P. foetida fruits were rich in amino [...] Read more.

The aim of this work was to evaluate the main nutrients and their antioxidant properties of a Chinese wild edible fruit, Passiflora foetida, collected from the ecoregion of Hainan province, China. The analytical results revealed that P. foetida fruits were rich in amino acids (1097 mg/100 g in total), minerals (595.75 mg/100 g in total), and unsaturated fatty acids (74.18 g/100 g in total fat). The lyophilized powder of edible portion contained the higher polyphenols content than the inedible portion powder. The UPLC-Q-TOF-MS^E analysis of the extractable and non-extractable phenolics indicated the presence of 65 compounds including 39 free phenolics, 14 insoluble-glycoside-phenolics, and 22 insoluble-ester-phenolics. In addition, the non-extractable phenolics obtained by alkali hydrolysis showed significant antioxidant activities by/through DPPH and ABTS radical scavenging. These findings of P. foetida fruits, for the first time, suggest that these polyphenol-rich fruits may have potential nutraceutical efficacies. Full article

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13 pages, 5945 KiB

Open AccessArticle

A Turn-on Fluorescence Sensor for Heparin Detection Based on a Release of Taiwan Cobra Cardiotoxin from a DNA Aptamer or Adenosine-Based Molecular Beacon

by Yi-Jun Shi¹, Liang-Jun Wang¹, Yuan-Chin Lee¹, Chia-Hui Huang¹, Wan-Ping Hu² and Long-Sen Chang^1,2,*

¹ Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan

² Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan

Molecules 2018, 23(2), 460; https://doi.org/10.3390/molecules23020460 - 19 Feb 2018

Cited by 6 | Viewed by 3582

Abstract

This study presents two sensitive fluorescent assays for sensing heparin on the basis of the electrostatic interaction between heparin and Naja naja atra cardiotoxin 3 (CTX3). Owing to CTX3-induced folded structure of an adenosine-based molecular beacon (MB) or a DNA aptamer against CTX3, [...] Read more.

This study presents two sensitive fluorescent assays for sensing heparin on the basis of the electrostatic interaction between heparin and Naja naja atra cardiotoxin 3 (CTX3). Owing to CTX3-induced folded structure of an adenosine-based molecular beacon (MB) or a DNA aptamer against CTX3, a reduction in the fluorescent signal of the aptamer or MB 5′-end labeled with carboxyfluorescein (FAM) and 3′-end labeled with 4-([4-(dimethylamino)phenyl]azo)-benzoic acid (DABCYL) was observed upon the addition of CTX3. The presence of heparin and formation of the CTX3–heparin complex caused CTX3 detachment from the MB or aptamer, and restoration of FAM fluorescence of the 5′-FAM-and-3′-DABCYL-labeled MB and aptamer was subsequently noted. Moreover, the detection of heparin with these CTX3-aptamer and CTX3-MB sensors showed high sensitivity and selectivity toward heparin over chondroitin sulfate and hyaluronic acid regardless of the presence of plasma. The limit of detection for heparin in plasma was determined to be 16 ng/mL and 15 ng/mL, respectively, at a signal-to-noise ratio of 3. This study validates the practical utility of the CTX3-aptamer and CTX3-MB systems for determining the concentration of heparin in a biological matrix. Full article

(This article belongs to the Section Analytical Chemistry)

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14 pages, 262 KiB

Open AccessArticle

A Comparative Assessment of Biological Effects and Chemical Profile of Italian Asphodeline lutea Extracts

by Dora Melucci¹, Marcello Locatelli^2,3,*, Clinio Locatelli¹, Alessandro Zappi¹, Francesco De Laurentiis¹, Simone Carradori²

, Cristina Campestre²

, Lidia Leporini², Gokhan Zengin⁴

, Carene Marie Nancy Picot⁵, Luigi Menghini²

and Mohamad Fawzi Mahomoodally⁵

¹ Department of Chemistry “G. Ciamician”, University of Bologna, 40126 Bologna, Italy

² Department of Pharmacy, University “G. D’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy

³ Interuniversity Consortium of Structural and Systems Biology, 00136 Rome, Italy

⁴ Department of Biology, Selcuk University, Campus, 42250, 42130 Konya, Turkey

⁵ Department of Health Sciences, University of Mauritius, Réduit 80837, Mauritius

Molecules 2018, 23(2), 461; https://doi.org/10.3390/molecules23020461 - 19 Feb 2018

Cited by 23 | Viewed by 4011

Abstract

The present study aims to highlight the therapeutic potential of Asphodeline lutea (AL), a wild edible plant of the Mediterranean diet. Roots, aerial parts, and flowers of AL at two different phenological stages were collected from three locations in Italy. The [...] Read more.

The present study aims to highlight the therapeutic potential of Asphodeline lutea (AL), a wild edible plant of the Mediterranean diet. Roots, aerial parts, and flowers of AL at two different phenological stages were collected from three locations in Italy. The inhibitory activities of extracts on strategic enzymes linked to human diseases were assessed. The antioxidant properties were evaluated in vitro, using six standard bioassays. The phenolic and anthraquinone profiles were also established using HPLC-PDA. Zinc, cadmium, lead, and copper contents were also determined. All the samples inhibited acetylcholinesterase (from 1.51 to 2.20 mg GALAEs/g extract), tyrosinase (from 7.50 to 25.3 mg KAEs/g extract), and α-amylase (from 0.37 to 0.51 mmol ACAEs/g extract). Aloe-emodin and physcion were present in all parts, while rhein was not detected. The phenolic profile and the heavy metals composition of specimens gathered from three different regions of Italy were different. It can be argued that samples collected near the street can contain higher concentrations of heavy metals. The experimental data confirm that the A. lutea species could be considered as a potential source of bioactive metabolites, and its consumption could play a positive and safe role in human health maintenance. Full article

(This article belongs to the Special Issue Innovative Extraction Techniques and Hyphenated Instrument Configuration for Complex Matrices Analysis)

15 pages, 1278 KiB

Open AccessArticle

Characterization of the Key Aroma Compounds in Proso Millet Wine Using Headspace Solid-Phase Microextraction and Gas Chromatography-Mass Spectrometry

by Jingke Liu^1,2,3,*

, Wei Zhao^1,2,3, Shaohui Li^1,2,3, Aixia Zhang^1,2,3, Yuzong Zhang^1,2,3 and Songyan Liu⁴

¹ Institute Millet Crops of Heibei Academy of Agriculture and Forestry, Shijiazhuang 050035, China

² National Millet Improvement Center of China, Shijiazhuang 050035, China

³ Minor Cereal Crops Research Laboratory of Hebei Province, Shijiazhuang 050035, China

⁴ Shijiazhuang Livestock Products Quality Inspection & Supervision Center, Shijiazhuang 050041, China

Molecules 2018, 23(2), 462; https://doi.org/10.3390/molecules23020462 - 20 Feb 2018

Cited by 25 | Viewed by 5141

Abstract

The volatile compounds in proso millet wine were extracted by headspace solid-phase microextraction (85 μm polyacrylate (PA), 100 μm polydimethylsiloxane (PDMS), 75 μm Carboxen (CAR)/PDMS, and 50/30 μm divinylbenzene (DVB)/CAR/PDMS fibers), and analyzed using gas chromatography-mass spectrometry; the odor characteristics and intensities were [...] Read more.

The volatile compounds in proso millet wine were extracted by headspace solid-phase microextraction (85 μm polyacrylate (PA), 100 μm polydimethylsiloxane (PDMS), 75 μm Carboxen (CAR)/PDMS, and 50/30 μm divinylbenzene (DVB)/CAR/PDMS fibers), and analyzed using gas chromatography-mass spectrometry; the odor characteristics and intensities were analyzed by the odor activity value (OAV). Different sample preparation factors were used to optimize this method: sample amount, extraction time, extraction temperature, and content of NaCl. A total of 64 volatile compounds were identified from the wine sample, including 14 esters, seven alcohols, five aldehydes, five ketones, 12 benzene derivatives, 12 hydrocarbons, two terpenes, three phenols, two acids, and two heterocycles. Ethyl benzeneacetate, phenylethyl alcohol, and benzaldehyde were the main volatile compounds found in the samples. According to their OAVs, 14 volatile compounds were determined to be odor-active compounds (OAV > 1), and benzaldehyde, benzeneacetaldehyde, 1-methyl-naphthalene, 2-methyl-naphthalene, and biphenyl were the prominent odor-active compounds (OAV > 50), having a high OAV. Principal component analysis (PCA) showed the difference of distribution of the 64 volatile compounds and 14 odor-active compounds with four solid-phase microextraction (SPME) fibers. Full article

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11 pages, 1350 KiB

Open AccessArticle

Qualitative and Quantitative Phytochemical Analysis of Different Extracts from Thymus algeriensis Aerial Parts

by Nassima Boutaoui¹, Lahcene Zaiter¹, Fadila Benayache¹, Samir Benayache¹

, Simone Carradori^2,*

, Stefania Cesa³

, Anna Maria Giusti⁴

, Cristina Campestre²

, Luigi Menghini²

, Denise Innosa⁵

and Marcello Locatelli²

¹ Unité de recherche Valorisation des Ressources Naturelles, Molécules Bioactives et Analyses Physicochimiques et Biologiques, Université Frères Mentouri, Constantine 1, Route d’Aïn El Bey, 25000 Constantine, Algérie

² Department of Pharmacy, University “G. d’Annunzio” of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy

³ Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, P.le Aldo Moro 5, 00185 Rome, Italy

⁴ Dipartimento di Medicina Sperimentale, Sapienza Università di Roma, P.le Aldo Moro 5, 00185 Rome, Italy

⁵ Facoltà di Bioscienze e tecnologie agro-alimentari e ambientali, Università di Teramo, Via Renato Balzarini 1, 64100 Teramo, Italy

Molecules 2018, 23(2), 463; https://doi.org/10.3390/molecules23020463 - 20 Feb 2018

Cited by 30 | Viewed by 5248

Abstract

This study was performed to evaluate the metabolite recovery from different extraction methods applied to Thymus algeriensis aerial parts. A high-performance liquid chromatographic method using photodiode array detector with gradient elution has been developed and validated for the simultaneous estimation of different phenolic [...] Read more.

This study was performed to evaluate the metabolite recovery from different extraction methods applied to Thymus algeriensis aerial parts. A high-performance liquid chromatographic method using photodiode array detector with gradient elution has been developed and validated for the simultaneous estimation of different phenolic compounds in the extracts and in their corresponding purified fractions. The experimental results show that microwave-assisted aqueous extraction for 15 min at 100 °C gave the most phenolics-enriched extract, reducing extraction time without degradation effects on bioactives. Sixteen compounds were identified in this extract, 11 phenolic compounds and five flavonoids, all known for their biological activities. Color analysis and determination of chlorophylls and carotenoids implemented the knowledge of the chemical profile of this plant. Full article

(This article belongs to the Special Issue Innovative Extraction Techniques and Hyphenated Instrument Configuration for Complex Matrices Analysis)

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15 pages, 3100 KiB

Open AccessArticle

Exploring the Metabolism of (+)-[¹⁸F]Flubatine In Vitro and In Vivo: LC-MS/MS Aided Identification of Radiometabolites in a Clinical PET Study †

by Friedrich-Alexander Ludwig^1,*, Steffen Fischer¹, René Smits², Winnie Deuther-Conrad¹

, Alexander Hoepping², Solveig Tiepolt³, Marianne Patt³, Osama Sabri^3,‡ and Peter Brust^1,‡

¹ Helmholtz-Zentrum Dresden-Rossendorf, Research Site Leipzig, Institute of Radiopharmaceutical Cancer Research, Permoserstraße 15, 04318 Leipzig, Germany

² ABX advanced biochemical compounds GmbH, Heinrich-Gläser-Straße 10-14, 01454 Radeberg, Germany

³ Department of Nuclear Medicine, University Hospital Leipzig, Liebigstraße 18, 04103 Leipzig, Germany

^† This publication is dedicated to Jörg Steinbach on the occasion of his 65th birthday.

^‡ These authors contributed equally to this work.

Molecules 2018, 23(2), 464; https://doi.org/10.3390/molecules23020464 - 20 Feb 2018

Cited by 8 | Viewed by 4969

Abstract

Both (+)-[¹⁸F]flubatine and its enantiomer (−)-[¹⁸F]flubatine are radioligands for the neuroimaging of α4β2 nicotinic acetylcholine receptors (nAChRs) by positron emission tomography (PET). In a clinical study in patients with early Alzheimer’s disease, (+)-[¹⁸F]flubatine ((+)-[¹⁸F]1 [...] Read more.

Both (+)-[¹⁸F]flubatine and its enantiomer (−)-[¹⁸F]flubatine are radioligands for the neuroimaging of α4β2 nicotinic acetylcholine receptors (nAChRs) by positron emission tomography (PET). In a clinical study in patients with early Alzheimer’s disease, (+)-[¹⁸F]flubatine ((+)-[¹⁸F]1) was examined regarding its metabolic fate, in particular by identification of degradation products detected in plasma and urine. The investigations included an in vivo study of (+)-flubatine ((+)-1) in pigs and structural elucidation of formed metabolites by LC-MS/MS. Incubations of (+)-1 and (+)-[¹⁸F]1 with human liver microsomes were performed to generate in vitro metabolites, as well as radiometabolites, which enabled an assignment of their structures by comparison of LC-MS/MS and radio-HPLC data. Plasma and urine samples taken after administration of (+)-[¹⁸F]1 in humans were examined by radio-HPLC and, on the basis of results obtained in vitro and in vivo, formed radiometabolites were identified. In pigs, (+)-1 was monohydroxylated at different sites of the azabicyclic ring system of the molecule. Additionally, one intermediate metabolite underwent glucuronidation, as also demonstrated in vitro. In humans, a fraction of 95.9 ± 1.9% (n = 10) of unchanged tracer remained in plasma, 30 min after injection. However, despite the low metabolic degradation, both radiometabolites formed in humans could be characterized as (i) a product of C-hydroxylation at the azabicyclic ring system, and (ii) a glucuronide conjugate of the precedingly-formed N8-hydroxylated (+)-[¹⁸F]1. Full article

(This article belongs to the Special Issue Current Aspects of Radiopharmaceutical Chemistry)

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12 pages, 3034 KiB

Open AccessArticle

Comparison of Inhibitory Capacities of 6-, 8- and 10-Gingerols/Shogaols on the Canonical NLRP3 Inflammasome-Mediated IL-1β Secretion

by Su-Chen Ho^* and Yi-Huang Chang

Department of Food Science, Yuanpei University of Medical Technology, Hsinchu 300, Taiwan

Molecules 2018, 23(2), 466; https://doi.org/10.3390/molecules23020466 - 21 Feb 2018

Cited by 45 | Viewed by 5586

Abstract

Endogenous noninfectious substances that mediate the nucleotide oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation and interleukin (IL)-1β secretion causes inappropriate sterile inflammation and is implicated in the pathogenesis of several chronic diseases, such as type 2 diabetes mellitus, gout, [...] Read more.

Endogenous noninfectious substances that mediate the nucleotide oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation and interleukin (IL)-1β secretion causes inappropriate sterile inflammation and is implicated in the pathogenesis of several chronic diseases, such as type 2 diabetes mellitus, gout, atherosclerosis and Alzheimer’s disease. Consequently, dietary phytochemicals exhibiting capacities to suppress canonical NLRP3 inflammasome-mediated IL-1β secretion can be a reliable supplement to prevent such diseases. The purpose of this study was to investigate and compare the inhibitory effects of ginger phytochemicals, including 6-, 8- and 10-gingerols/shogaols on the canonical NLRP3 inflammasome-mediated IL-1β secretion in THP-1 macrophages with ordered stimulations of lipopolysaccharide (LPS) and adenosine 5′-triphosphate (ATP). At 20 μM, the 10-gingerol and all the shogaols significantly inhibited canonical IL-1β secretion. The shogaols had a more potent inhibitory capacity than that of corresponding gingerols. Increase of alkyl chain length impacted negatively the inhibitory activity of shogaols. Additionally, these effective ginger phytochemicals not only inhibited the LPS-primed expression of pro-IL-1β and NLRP3, but also decreased ATP-activated caspase-1. The results demonstrated that ginger phytochemicals, especially the most potent, 6-shogaol, might be promising for developing as an inhibitor of the canonical NLRP3 inflammasome-mediated IL-1β secretion and further applied in prevention of NLRP3 inflammasome-associated diseases. Full article

(This article belongs to the Special Issue Biological Activity of Secondary Metabolites)

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13 pages, 2813 KiB

Open AccessFeature PaperArticle

A Hexahomotrioxacalix[3]arene-Based Ditopic Receptor for Alkylammonium Ions Controlled by Ag⁺ Ions

by Xue-Kai Jiang¹, Yusuke Ikejiri¹, Chong Wu¹, Shofiur Rahman², Paris E. Georghiou², Xi Zeng³, Mark R. J. Elsegood⁴

, Carl Redshaw⁵

, Simon J. Teat⁶ and Takehiko Yamato^1,*

¹ Department of of Applied Chemistry, Faculty of Science and Engineering, Saga University, Honjo-machi 1, Saga 840-8502 Japan

² Department of Chemistry, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador A1B 3X7, Canada

³ Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Guizhou University, Guiyang, Guizhou, 550025, China

⁴ Chemistry Department, Loughborough University, Loughborough, LE11 3TU, UK

⁵ Chemisty, School of Mathematics and Physical Sciences, The University of Hull, Cottingham Road, Hull, Yorkshire, HU6 7RX, UK

⁶ ALS, Berkeley Lab, 1 Cyclotron Road, Berkeley, CA 94720, USA

Molecules 2018, 23(2), 467; https://doi.org/10.3390/molecules23020467 - 21 Feb 2018

Cited by 3 | Viewed by 2974

Abstract

A receptor cone-1 based on a hexahomotrioxacalix[3]arene bearing three pyridyl groups was successfully synthesized, which has a C₃-symmetric conformation and is capable of binding alkylammonium and metal ions simultaneously in a cooperative fashion. It can bind alkylammonium ions through the [...] Read more.

A receptor cone-1 based on a hexahomotrioxacalix[3]arene bearing three pyridyl groups was successfully synthesized, which has a C₃-symmetric conformation and is capable of binding alkylammonium and metal ions simultaneously in a cooperative fashion. It can bind alkylammonium ions through the -cavity formed by three aryl rings. This behaviour is consistent with the cone-in/cone-out conformational rearrangement needed to reorganize the cavity for endo-complexation. As a C₃-symmetrical pyridyl-substituted calixarene, receptor cone-1 can also bind an Ag⁺ ion, and the nitrogen atoms are turned towards the inside of the cavity and interact with Ag⁺. After complexation of tris(2-pyridylamide) derivative receptor cone-1 with Ag⁺, the original C₃-symmetry was retained and higher complexation selectivity for n-BuNH₃⁺ versus t-BuNH₃⁺ wasobserved. Thus, it is believed that this receptor will have a role to play in the sensing, detection, and recognition of Ag⁺ and n-BuNH₃⁺ions. Full article

(This article belongs to the Section Organic Chemistry)

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7 pages, 2611 KiB

Open AccessFeature PaperArticle

Tandem Lewis Pair Polymerization and Organocatalytic Ring-Opening Polymerization for Synthesizing Block and Brush Copolymers

by Xing-Yu Sun, Wei-Min Ren^*, Si-Jie Liu, Yin-Bao Jia, Yi-Ming Wang and Xiao-Bing Lu^*

State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China

Molecules 2018, 23(2), 468; https://doi.org/10.3390/molecules23020468 - 21 Feb 2018

Cited by 8 | Viewed by 3771

Abstract

Lewis pair polymerization is a powerful method for preparing soluble polymers bearing pendant active vinyl groups by directly polymerizing dissymmetric divinyl polar monomers. Herein, we present a strategy for synthesizing block and brush copolymers via tandem Lewis pair polymerization of methacrylates, “thiol-ene” click [...] Read more.

Lewis pair polymerization is a powerful method for preparing soluble polymers bearing pendant active vinyl groups by directly polymerizing dissymmetric divinyl polar monomers. Herein, we present a strategy for synthesizing block and brush copolymers via tandem Lewis pair polymerization of methacrylates, “thiol-ene” click reaction and organocatalytic ring-opening polymerization of lactide. Full article

(This article belongs to the Special Issue Lewis Pair Polymerization for New Reactivity and Structure in Polymer Synthesis)

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14 pages, 2179 KiB

Open AccessArticle

Identification and Characterization of Phenylpropanoid Biosynthetic Genes and Their Accumulation in Bitter Melon (Momordica charantia)

by Do Manh Cuong^1,†, Soon-Jae Kwon^2,†

, Jin Jeon¹, Yun Ji Park¹, Jong Seok Park³ and Sang Un Park^1,*

¹ Department of Crop Science, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea

² Korea Atomic Energy Research Institute, Advanced Radiation Technology Institute, 29 Geumgu-gil, Jeongeup-si, Jeollabuk-do 56212, Korea

³ Department of Horticulture, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 469; https://doi.org/10.3390/molecules23020469 - 21 Feb 2018

Cited by 16 | Viewed by 6155

Abstract

Phenylpropanoids and flavonoids belong to a large group of secondary metabolites, and are considered to have antioxidant activity, which protects the cells against biotic and abiotic stresses. However, the accumulation of phenylpropanoids and flavonoids in bitter melon has rarely been studied. Here, we [...] Read more.

Phenylpropanoids and flavonoids belong to a large group of secondary metabolites, and are considered to have antioxidant activity, which protects the cells against biotic and abiotic stresses. However, the accumulation of phenylpropanoids and flavonoids in bitter melon has rarely been studied. Here, we identify ten putative phenylpropanoid and flavonoid biosynthetic genes in bitter melon. Most genes were highly expressed in leaves and/or flowers. HPLC analysis showed that rutin and epicatechin were the most abundant compounds in bitter melon. Rutin content was the highest in leaves, whereas epicatechin was highly accumulated in flowers and fruits. The accumulation patterns of trans-cinnamic acid, p-coumaric acid, ferulic acid, kaempferol, and rutin coincide with the expression patterns of McPAL, McC4H, McCOMT, McFLS, and Mc3GT, respectively, suggesting that these genes play important roles in phenylpropanoid and flavonoid biosynthesis in bitter melon. In addition, we also investigated the optimum light conditions for enhancing phenylpropanoid and flavonoid biosynthesis and found that blue light was the most effective wavelength for enhanced accumulation of phenylpropanoids and flavonoids in bitter melon. Full article

(This article belongs to the Section Bioorganic Chemistry)

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13 pages, 261 KiB

Open AccessArticle

Effect of the New Plant Growth Biostimulants Based on Amino Acids on Yield and Grain Quality of Winter Wheat

by Małgorzata Popko¹, Izabela Michalak^1,*

, Radosław Wilk¹, Mateusz Gramza², Katarzyna Chojnacka¹ and Henryk Górecki¹

¹ Department of Advanced Material Technologies, Faculty of Chemistry, Wrocław University of Science and Technology, Smoluchowskiego 25, 50-372 Wrocław, Poland

² AGRECO Ltd., Wrocław, al. Lipowa 21/1, 53-124 Wrocław, Poland

Molecules 2018, 23(2), 470; https://doi.org/10.3390/molecules23020470 - 21 Feb 2018

Cited by 160 | Viewed by 10453

Abstract

Field and laboratory experiments were carried out in 2012–2013, aimed at evaluating the influence of new products stimulating plant growth based on amino acids on crop yield, characteristics of grain and content of macro- and micronutrients in winter wheat (Triticum aestivum L.). [...] Read more.

Field and laboratory experiments were carried out in 2012–2013, aimed at evaluating the influence of new products stimulating plant growth based on amino acids on crop yield, characteristics of grain and content of macro- and micronutrients in winter wheat (Triticum aestivum L.). The tests included two formulations produced in cooperation with INTERMAG Co. (Olkusz, Poland)—AminoPrim and AminoHort, containing 15% and 20% amino acids, respectively, and 0.27% and 2.1% microelements, respectively. Field experiments showed that the application of products based on amino acids influenced the increase of grain yield of winter wheat (5.4% and 11%, respectively, for the application of AminoPrim at a dose 1.0 L/ha and AminoHort at dose 1.25 L/ha) when compared to the control group without biostimulant. Laboratory tests showed an increase of technological characteristics of grain such as ash content, Zeleny sedimentation index and content of protein. The use of the tested preparations at different doses also contributed to the increase of the nutrients content in grains, in particular copper (ranging 31–50%), as well as sodium (35–43%), calcium (4.3–7.9%) and molybdenum (3.9–16%). Biostimulants based on amino acids, tested in the present study, can be recommended for an efficient agricultural production. Full article

14 pages, 8169 KiB

Open AccessArticle

Inhibitory Effects of a Variety of Aldehydes on Amaranthus tricolor L. and Echinochloa crus-galli (L.) Beauv.

by Nawasit Chotsaeng^1,*

, Chamroon Laosinwattana² and Patchanee Charoenying¹

¹ Department of Chemistry, Faculty of Science, King Mongkut’s Institute of Technology Ladkrabang, Bangkok 10520, Thailand

² Department of Plant Production Technology, Faculty of Agricultural Technology, King Mongkut’s Institute of Technology Ladkrabang, Bangkok 10520, Thailand

Molecules 2018, 23(2), 471; https://doi.org/10.3390/molecules23020471 - 21 Feb 2018

Cited by 15 | Viewed by 4846

Abstract

Thirty-seven commercial aldehydes containing aliphatic chains and aromatic rings as well as heteroaromatic rings were evaluated for their inhibitory activities against Chinese amaranth (Amaranthus tricolor L.) and barnyardgrass (Echinochloa crus-galli (L.) Beauv). Polysorbate 80 (Tween^® 80) was used as a [...] Read more.

Thirty-seven commercial aldehydes containing aliphatic chains and aromatic rings as well as heteroaromatic rings were evaluated for their inhibitory activities against Chinese amaranth (Amaranthus tricolor L.) and barnyardgrass (Echinochloa crus-galli (L.) Beauv). Polysorbate 80 (Tween^® 80) was used as a surfactant and the research was preliminarily conducted at 400 μM of all aldehydes. Among these aldehydes, (E)-cinnamaldehyde (7) showed the greatest inhibitory effect on seed germination, shoot and root growth of Chinese amaranth by 54.55%, 75.53%, and 85.13% respectively. Similarly, (E)-crotonaldehyde (5), a related α,β-unsaturated aldehyde, inhibited the germination and seedling growth of the tested species at a high percentage. Apart from these two unsaturated aldehydes, no other aliphatic aldehydes had a harmful effect on Chinese amaranth. In terms of benzaldehyde (6), it had no effect on the tested plant; however, many of its derivatives displayed some inhibitory activity. Furthermore, for the ten common heteroaromatic aldehydes, picolinaldehyde (32) had a high inhibitory effect on Chinese amaranth which closely related to the effect of (E)-crotonaldehyde (5) and (E)-cinnamaldehyde (7), whereas, other heteroaromatic aldehydes showed lower effects. In the case of a monocot plant, barnyardgrass, no tested aldehydes reduced seed germination, however, (E)-cinnamaldehyde (7), 2,4,6-trimethoxybenzaldehyde (16) and 4-(dimethylamino)benzaldehyde (24) could inhibit the seedling growth of the plant with low to moderate levels. The herbicidal effects of the most active aldehydes were then further investigated in order to find the minimum concentration of these aldehydes suppressing the germination and growth of the tested plants. At concentrations as low as 50–100 μM some aldehydes could inhibit the seedling growth of the tested species. The structure-activity relationship (SAR) study reported here demonstrates the chemical clues governing the inhibitory activity of aldehydes which could be utilized in the development of highly effective herbicides in the near future. Full article

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9 pages, 589 KiB

Open AccessArticle

Bioactive Phenolic and Isocoumarin Glycosides from the Stems of Homalium paniculiflorum

by Shou-Yuan Wu^1,†, Yan-Hui Fu^1,†, Qi Zhou¹, Meng Bai¹, Guang-Ying Chen¹, Si-Yu Zhao¹, Chang-Ri Han^2,* and Xiao-Ping Song^1,*

¹ Key Laboratory of Tropical Medicinal Plant Chemistry of Ministry of Education, Hainan Normal University, Haikou 571158, China

² Key Laboratory of Medicinal and Edible Plants Resources of Hainan Province, Hainan Institute of Science and Technology, HaiKou 571126, China

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 472; https://doi.org/10.3390/molecules23020472 - 22 Feb 2018

Cited by 7 | Viewed by 4491

Abstract

Two new phenolic glycosides (1 and 2) and two new isocoumarin glycosides (3 and 4), along with 14 known compounds (5–18), were isolated from the stems of Homalium paniculiflorum. Their structures were established on [...] Read more.

Two new phenolic glycosides (1 and 2) and two new isocoumarin glycosides (3 and 4), along with 14 known compounds (5–18), were isolated from the stems of Homalium paniculiflorum. Their structures were established on the basis of extensive spectroscopic analyses and chemical methods. All new compounds were evaluated for their anti-inflammatory activities via examining the inhibitory activity on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in mouse macrophage RAW 264.7 cells in vitro. Compounds 1 and 4 exhibited inhibitory activities with IC₅₀ values of 30.23 ± 1.23 μM and 19.36 ± 0.19 μM, respectively. Full article

(This article belongs to the Collection Bioactive Compounds)

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16 pages, 1977 KiB

Open AccessArticle

Assessment of Chitosan-Based Hydrogel and Photodynamic Inactivation against Propionibacterium acnes

by Maria Lucia Frade^1,†, Sarah Raquel De Annunzio^1,†, Giovana Maria Fioramonti Calixto²

, Francesca Damiani Victorelli², Marlus Chorilli²

and Carla Raquel Fontana^1,*

¹ Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), 14800-903 Araraquara, São Paulo, Brazil

² Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), 14800-903 Araraquara, São Paulo, Brazil

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 473; https://doi.org/10.3390/molecules23020473 - 22 Feb 2018

Cited by 43 | Viewed by 4861

Abstract

Chitosan (CH) is a biopolymer that exhibits a number of interesting properties such as anti-inflammatory and antibacterial activity and is also a promising platform for the incorporation of photosensitizing agents. This study aimed to evaluate the efficacy of antimicrobial activity of chitosan hydrogel [...] Read more.

Chitosan (CH) is a biopolymer that exhibits a number of interesting properties such as anti-inflammatory and antibacterial activity and is also a promising platform for the incorporation of photosensitizing agents. This study aimed to evaluate the efficacy of antimicrobial activity of chitosan hydrogel formulation alone and in combination with the methylene blue (MB) associated with antimicrobial photodynamic therapy (aPDT) against planktonic and biofilm phase of Propionibacterium acnes. Suspensions were sensitized with 12.5, 25.0, 37.5, 50.0 μg/mL of MB for 10 min and biofilms to 75, 100 and 150 μg/mL for 30 min then exposed to red light (660 nm) at 90 J/cm² and 150 J/cm² respectively. After treatments, survival fractions were calculated by counting the number of colony-forming units. The lethal effect of aPDT associated with CH hydrogel in planktonic phase was achieved with 12.5 µg/mL MB and 1.9 log₁₀ biofilm reduction using 75 µg/mL MB. Rheological studies showed that formulations exhibited pseudoplastic non-Newtonian behavior without thixotropy. Bioadhesion test evidenced that the formulations are highly adhesive to skin and the incorporation of MB did not influence the bioadhesive force of the formulations. Full article

(This article belongs to the Special Issue Chitin and Chitosan Derivatives: Biological Activities and Application)

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9 pages, 3373 KiB

Open AccessArticle

A Novel Dicyanoisophorone-Based Ratiometric Fluorescent Probe for Selective Detection of Cysteine and Its Bioimaging Application in Living Cells

by Hengrui Zhang, Nan Qin and Zhijie Fang^*

School of Chemical Engineering, Nanjing University of Science & Technology, 200 Xiao Ling Wei, Nanjing 210094, China

Molecules 2018, 23(2), 475; https://doi.org/10.3390/molecules23020475 - 22 Feb 2018

Cited by 17 | Viewed by 4128

Abstract

A selective and ratiometric turn-on fluorescent probe was designed and synthesized by using a novel dicyanoisophorone-based derivative and acrylate moiety. The probe displayed high stability and good selectivity to cysteine (Cys) over homocysteine (Hcy) and glutathione (GSH). It also exhibited rapid response to [...] Read more.

A selective and ratiometric turn-on fluorescent probe was designed and synthesized by using a novel dicyanoisophorone-based derivative and acrylate moiety. The probe displayed high stability and good selectivity to cysteine (Cys) over homocysteine (Hcy) and glutathione (GSH). It also exhibited rapid response to Cys within 180 s. Most importantly, the fluorescence intensity ratio at 590 and 525 nm (I₅₉₀/I₅₂₅) was linearly dependent on the Cys concentration in the range from 0 to 40 μM and the detection limit calculated to be 0.48 μM. This probe was also applied for bioimaging of intracellular Cys in living HeLa cells with low cytotoxicity. Full article

(This article belongs to the Section Analytical Chemistry)

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13 pages, 2360 KiB

Open AccessArticle

Study of Hexane Adsorption on Activated Carbons with Differences in Their Surface Chemistry

by Diana Hernández-Monje¹, Liliana Giraldo² and Juan Carlos Moreno-Piraján^3,*

¹ Departamento de Química, Facultad de Ciencias, Universidad Nacional de Colombia, Sede Bogotá, Carrera 30 No 45-03, Bogotá 111321, Colombia

² Departamento de Química, Facultad de Ciencias, Universidad Nacional de Colombia, Sede Bogotá, Carrera 30 No 45-03, Bogotá 111321, Colombia

³ Departamento de Química, Facultad de Ciencias, Universidad de los Andes, Carrera 1 este No 18A-10, Bogotá 111321, Colombia

Molecules 2018, 23(2), 476; https://doi.org/10.3390/molecules23020476 - 22 Feb 2018

Cited by 13 | Viewed by 4089

Abstract

The study of aliphatic compounds adsorption on activated carbon can be carried out from the energetic change involved in the interaction; the energy values can be determined from isotherms or by the immersion enthalpy. Vapor phase adsorption isotherms of hexane at 263 K [...] Read more.

The study of aliphatic compounds adsorption on activated carbon can be carried out from the energetic change involved in the interaction; the energy values can be determined from isotherms or by the immersion enthalpy. Vapor phase adsorption isotherms of hexane at 263 K on five activated carbons with different content of oxygenated groups and the immersion enthalpy of the activated carbons in hexane and water were determined in order to characterize the interactions in the solid–liquid system, and for calculating the hydrophobic factor of the activated carbons. The micropore volume and characteristic energy from adsorption isotherms of hexane, the BET (Brunauer–Emmett–Teller) surface area from the adsorption isotherms of N₂, and the area accessible to the hexane from the immersion enthalpy were calculated. The activated carbon with the lowest content of oxygenated groups (0.30 µmolg⁻¹) and the highest surface area (996 m²g⁻¹) had the highest hexane adsorption value: 0.27 mmol g⁻¹; the values for E_o were between 5650 and 6920 Jmol⁻¹ and for ΔH_im were between −66.1 and −16.4 Jg⁻¹. These determinations allow us to correlate energetic parameters with the surface area and the chemical modifications that were made to the solids, where the surface hydrophobic character of the activated carbon favors the interaction. Full article

(This article belongs to the Section Physical Chemistry)

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15 pages, 2102 KiB

Open AccessArticle

Structure-Antiplatelet Activity Relationships of Novel Ruthenium (II) Complexes: Investigation of Its Molecular Targets

by Chih-Hsuan Hsia¹, Thanasekaran Jayakumar¹, Joen-Rong Sheu¹, Shin-Yi Tsao², Marappan Velusamy³, Chih-Wei Hsia¹, Duen-Suey Chou¹, Chao-Chien Chang⁴, Chi-Li Chung⁵

, Themmila Khamrang^1,3,* and Kao-Chang Lin^1,6,*

¹ Graduate Institute of Medical Sciences and Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei 110, Taiwan

² Division of Endocrinology & Metabolism, Department of Internal Medicine, Sijhih Cathay General Hospital, New Taipei 22174, Taiwan

³ Department of Chemistry, North Eastern Hill University, Shillong 793022, India

⁴ Department of Cardiology, Cathay General Hospital, Taipei 106, Taiwan

⁵ Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 106, Taiwan

⁶ Department of Neurology, Chi Mei Medical Center, Tainan 710, Taiwan

Molecules 2018, 23(2), 477; https://doi.org/10.3390/molecules23020477 - 22 Feb 2018

Cited by 4 | Viewed by 2965

Abstract

The regulation of platelet function by pharmacological agents that modulate platelet signaling has proven to be a positive approach to the prevention of thrombosis. Ruthenium complexes are fascinating for the development of new drugs, as they possess numerous chemical and biological properties. The [...] Read more.

The regulation of platelet function by pharmacological agents that modulate platelet signaling has proven to be a positive approach to the prevention of thrombosis. Ruthenium complexes are fascinating for the development of new drugs, as they possess numerous chemical and biological properties. The present study aims to evaluate the structure-activity relationship (SAR) of newly synthesized ruthenium (II) complexes, TQ-1, TQ-2 and TQ-3 in agonists-induced washed human platelets. Silica gel column chromatography, aggregometry, immunoblotting, NMR, and X-ray analyses were performed in this study. Of the three tested compounds, TQ-3 showed a concentration (1–5 μM) dependent inhibitory effect on platelet aggregation induced by collagen (1 μg/mL) and thrombin (0.01 U/mL) in washed human platelets; however, TQ-1 and TQ-2 had no response even at 250 μM of collagen and thrombin-induced aggregation. TQ-3 was effective with inhibiting collagen-induced ATP release, calcium mobilization ([Ca²⁺]i) and P-selectin expression without cytotoxicity. Moreover, TQ-3 significantly abolished collagen-induced Lyn-Fyn-Syk, Akt-JNK and p38 mitogen-activated protein kinases (p38 MAPKs) phosphorylation. The compound TQ-3 containing an electron donating amino group with two phenyl groups of the quinoline core could be accounted for by its hydrophobicity and this nature might be the reason for the noted antiplatelet effects of TQ-3. The present results provide a molecular basis for the inhibition by TQ-3 in collagen-induced platelet aggregation, through the suppression of multiple machineries of the signaling pathway. These results may suggest that TQ-3 can be considered a potential agent for the treatment of vascular diseases. Full article

(This article belongs to the Section Inorganic Chemistry)

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12 pages, 1656 KiB

Open AccessArticle

Phycocyanin Protects Against UVB-induced Apoptosis Through the PKC α/βII-Nrf-2/HO-1 Dependent Pathway in Human Primary Skin Cells

by Ki Mo Kim^1,2, Joo Young Lee¹

, A-Rang Im¹ and Sungwook Chae^2,*

¹ KM Convergence Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Korea

² Department of Korean Life Science and Technology, Korea University of Science and Technology, Daejeon 34113, Korea

Molecules 2018, 23(2), 478; https://doi.org/10.3390/molecules23020478 - 22 Feb 2018

Cited by 32 | Viewed by 6301

Abstract

Phycocyanin (Pc) is one of the active pigment constituents of Spirulina microalgae. It has been used for its potent antioxidant and anti-inflammatory properties. However, the protective effects of Pc against ultraviolet-B (UVB)-induced primary skin cells damage are still undefined. In the present study, [...] Read more.

Phycocyanin (Pc) is one of the active pigment constituents of Spirulina microalgae. It has been used for its potent antioxidant and anti-inflammatory properties. However, the protective effects of Pc against ultraviolet-B (UVB)-induced primary skin cells damage are still undefined. In the present study, we investigated whether Pc prevented UVB-induced apoptotic cell death in human dermal fibroblasts (HDF) and human epidermal keratinocytes (HEK). Pc induced the transcription of heme oxygenase-1 (HO-1). Furthermore, Pc treatments resulted in a marked increase in nuclear factor erythroid-derived 2 (NF-E2)-like 2 (Nrf-2) nuclear translocation. Also, Pc protected UVB induced apoptosis and reduced the p53 and Bax levels, as well as caspase-3 activation. Pc treatment showed a significantly enhanced effect on the phosphorylation of protein kinase C (PKC) α/β II, but not that of p38 mitogen-activated protein kinase (MAPK) or Akt. Induction of HO-1 induced by Pc was suppressed by Go6976, a selective inhibitor of PKC α/β II. In addition, knockdown of HO-1 by small interfering (siRNA) caused a significant increase in poly (ADP-ribose) polymerase 1 (PARP-1) cleavage and caspase-3 activation after Pc pretreatment. Taken together, our results demonstrate that Pc-induced expression of HO-1 is mediated by the PKC α/β II-Nrf-2/HO-1 pathway, and inhibits UVB-induced apoptotic cell death in primary skin cells. Full article

(This article belongs to the Section Natural Products Chemistry)

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25 pages, 7042 KiB

Open AccessFeature PaperArticle

Recognition of AMP, ADP and ATP through Cooperative Binding by Cu(II) and Zn(II) Complexes Containing Urea and/or Phenylboronic—Acid Moieties

by Israel Carreira-Barral^1,2

, Isabel Fernández-Pérez¹, Marta Mato-Iglesias¹, Andrés De Blas¹

, Carlos Platas-Iglesias¹ and David Esteban-Gómez^1,*

¹ Departamento de Química, Facultade de Ciencias, Universidade da Coruña, Centro de Investigacións Científicas Avanzadas (CICA), 15071 A Coruña, Galicia, Spain

² Departamento de Química, Facultad de Ciencias, Universidad de Burgos, 09001 Burgos, Spain

Molecules 2018, 23(2), 479; https://doi.org/10.3390/molecules23020479 - 22 Feb 2018

Cited by 17 | Viewed by 6890

Abstract

We report a series of Cu(II) and Zn(II) complexes with different ligands containing a dipicolyl unit functionalized with urea groups that may contain or not a phenylboronic acid function. These complexes were designed for the recognition of phosphorylated anions through coordination to the [...] Read more.

We report a series of Cu(II) and Zn(II) complexes with different ligands containing a dipicolyl unit functionalized with urea groups that may contain or not a phenylboronic acid function. These complexes were designed for the recognition of phosphorylated anions through coordination to the metal ion reinforced by hydrogen bonds involving the anion and NH groups of urea. The complexes were isolated and several adducts with pyrophosphate were characterized using X-ray diffraction measurements. Coordination of one of the urea nitrogen atoms to the metal ion promoted the hydrolysis of the ligands containing 1,3-diphenylurea units, while ligands bearing 1-ethyl-3-phenylurea groups did not hydrolyze significantly at room temperature. Spectrophotometric titrations, combined with ¹H and ³¹P NMR studies, were used in investigating the binding of phosphate, pyrophosphate (PPi), and nucleoside 5′-polyphosphates (AMP, ADP, ATP, CMP, and UMP). The association constants determined in aqueous solution (pH 7.0, 0.1 M MOPS) point to a stronger association with PPi, ADP, and ATP as compared with the anions containing a single phosphate unit. The [CuL⁴]²⁺ complex shows important selectivity for pyrophosphate (PPi) over ADP and ATP. Full article

(This article belongs to the Special Issue Coordination Chemistry for Devices and Functional Materials)

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15 pages, 13188 KiB

Open AccessArticle

Antioxidant Activity and Protective Effects of Enzyme-Extracted Oudemansiella radiata Polysaccharides on Alcohol-Induced Liver Injury

by Xiuxiu Wang^1,2,†, Min Liu^2,†, Chen Zhang^2,†, Shangshang Li^2,†, Qihang Yang², Jianjun Zhang², Zhiyuan Gong¹, Jiandong Han^1,* and Le Jia^2,*

¹ Institute of Agricultural Resources and Environment, Shandong Academy of Agricultural Science, Key Laboratory of Wastes Matrix Utilization, Ministry of Agriculture, Jinan 250100, China

² College of Life Science, Shandong Agricultural University, Taian 271018, China

^† These authors contributed equally to this manuscript.

Molecules 2018, 23(2), 481; https://doi.org/10.3390/molecules23020481 - 23 Feb 2018

Cited by 29 | Viewed by 5507

Abstract

This work was to examine the antioxidation in vitro and hepatoprotective effects of enzyme-extracted Oudemansiella radiata polysaccharides (En-OPS) on alcohol-induced liver damage in mice. The antioxidant activities were determined according to the scavenging effects of En-OPS on hydroxyl, superoxide, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, [...] Read more.

This work was to examine the antioxidation in vitro and hepatoprotective effects of enzyme-extracted Oudemansiella radiata polysaccharides (En-OPS) on alcohol-induced liver damage in mice. The antioxidant activities were determined according to the scavenging effects of En-OPS on hydroxyl, superoxide, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, and the level of reducing power. En-OPS showed hepatoprotective activities on decreasing the serum levels of aspertate aminotransferase (AST), alamine aminotransferase (ALT), and alkaline phosphatase (ALP), as well as hepatic lipid levels of total cholesterol (TC) and triacylglycerols (TG). En-OPS treatment reversed the acute impairment induced by alcohol consumption, including reactive oxygen species (ROS) generation, malondialdehyde (MAD), and lipid peroxide (LPO) elevation; and superoxide dismutase (SOD), GSH peroxide (GSH-Px), catalase (CAT), and total antioxidant capacity (T-AOC) impairment. The En-OPS effectively ameliorated alcohol metabolism by activating alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), and reducing cytochrome P450 2E1 (CYP2E1) levels. Furthermore, the histopathological observations also displayed that En-OPS could alleviate liver damage. These results indicated that En-OPS could be suitable to be an ingredient of preventing alcoholic liver diseases (ALD). In addition, the preliminary structure characteristics of En-OPS were also analyzed by Fourier transform infrared (FT-IR) spectroscopy and a gas chromatography-flame ionization detector (GC-FID). Full article

(This article belongs to the Special Issue Advances in Natural Polysaccharides Research)

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13 pages, 1333 KiB

Open AccessFeature PaperArticle

Antimicrobial and Antibiofilm Activity and Machine Learning Classification Analysis of Essential Oils from Different Mediterranean Plants against Pseudomonas aeruginosa

by Marco Artini^1,†, Alexandros Patsilinakos^2,3,4,†

, Rosanna Papa¹

, Mijat Božović^2,5

, Manuela Sabatino^2,3

, Stefania Garzoli²

, Gianluca Vrenna¹, Marco Tilotta¹, Federico Pepi², Rino Ragno^2,3,4,*

and Laura Selan¹

¹ Department of Public Health and Infectious Diseases, Sapienza University, P.le Aldo Moro 5, 00185 Rome, Italy

² Department of Drug Chemistry and Technology, Sapienza University, P.le Aldo Moro 5, 00185 Rome, Italy

³ Rome Center for Molecular Design, Department of Drug Chemistry and Technology, Sapienza University, P.le Aldo Moro 5, 00185 Rome, Italy

⁴ Alchemical Dynamics s.r.l., 00125 Rome, Italy

⁵ Faculty of Natural Sciences and Mathematics, University of Montenegro, Džordža Vašingtona bb, 81000 Podgorica, Montenegro

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 482; https://doi.org/10.3390/molecules23020482 - 23 Feb 2018

Cited by 63 | Viewed by 8148

Abstract

Pseudomonas aeruginosa is a ubiquitous organism and opportunistic pathogen that can cause persistent infections due to its peculiar antibiotic resistance mechanisms and to its ability to adhere and form biofilm. The interest in the development of new approaches for the prevention and treatment [...] Read more.

Pseudomonas aeruginosa is a ubiquitous organism and opportunistic pathogen that can cause persistent infections due to its peculiar antibiotic resistance mechanisms and to its ability to adhere and form biofilm. The interest in the development of new approaches for the prevention and treatment of biofilm formation has recently increased. The aim of this study was to seek new non-biocidal agents able to inhibit biofilm formation, in order to counteract virulence rather than bacterial growth and avoid the selection of escape mutants. Herein, different essential oils extracted from Mediterranean plants were analyzed for their activity against P. aeruginosa. Results show that they were able to destabilize biofilm at very low concentration without impairing bacterial viability. Since the action is not related to a bacteriostatic/bactericidal activity on P. aeruginosa, the biofilm change of growth in presence of the essential oils was possibly due to a modulation of the phenotype. To this aim, application of machine learning algorithms led to the development of quantitative activity–composition relationships classification models that allowed to direct point out those essential oil chemical components more involved in the inhibition of biofilm production. The action of selected essential oils on sessile phenotype make them particularly interesting for possible applications such as prevention of bacterial contamination in the community and in healthcare environments in order to prevent human infections. We assayed 89 samples of different essential oils as P. aeruginosa anti-biofilm. Many samples inhibited P. aeruginosa biofilm at concentrations as low as 48.8 µg/mL. Classification of the models was developed through machine learning algorithms. Full article

(This article belongs to the Special Issue Essential Oils as Antimicrobial and Anti-infectious Agents)

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13 pages, 1232 KiB

Open AccessArticle

Persicaline, A New Antioxidant Sulphur-Containing Imidazoline Alkaloid from Salvadora persica Roots

by Mohamed Farag¹

, Wael M. Abdel-Mageed^1,2, Omer Basudan¹ and Ali El-Gamal^1,3,*

¹ Pharmacognosy Department, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

² Pharmacognosy Department, Faculty of Pharmacy, Assiut University, Assiut P.O. Box 71526, Egypt

³ Pharmacognosy Department, Faculty of Pharmacy, Mansoura University, El-Mansoura P.O. Box 35516, Egypt

Molecules 2018, 23(2), 483; https://doi.org/10.3390/molecules23020483 - 23 Feb 2018

Cited by 26 | Viewed by 5834

Abstract

Salvadora persica L. is a popular chewing stick commonly known as “miswak”. During our ongoing research activities on the chemical constituents of Salvadora persica roots, which is a new sulphur-containing imidazoline alkaloid 1,3-Dibenzyl-4-(1,2,3,4-tetrahydroxy-butyl)-1,3-dihydro-imidazole-2-thione, persicaline, (1) along with five known compounds ( [...] Read more.

Salvadora persica L. is a popular chewing stick commonly known as “miswak”. During our ongoing research activities on the chemical constituents of Salvadora persica roots, which is a new sulphur-containing imidazoline alkaloid 1,3-Dibenzyl-4-(1,2,3,4-tetrahydroxy-butyl)-1,3-dihydro-imidazole-2-thione, persicaline, (1) along with five known compounds (2–6) are identified. Compounds (2, 3) were reported for the first time from the family Salvadoraeceae. The structure of the new compound was established by extensive spectroscopic data and HR-MS. The antioxidant activities of the fractions and isolates were evaluated using different in vitro methods, such as DPPH, superoxide anion and nitric oxide radicals scavenging assays. Compound (1) showed a promising antioxidant activity with IC₅₀ 0.1, 0.08, and 0.09 µM in the three assays, respectively, comparable to ascorbic acid. Full article

(This article belongs to the Collection Bioactive Compounds)

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15 pages, 263 KiB

Open AccessArticle

Impact of Storage Conditions on the Stability of Predominant Phenolic Constituents and Antioxidant Activity of Dried Piper betle Extracts

by Ameena Ali^1,*

, Chien Hwa Chong²

, Siau Hui Mah³

, Luqman Chuah Abdullah⁴

, Thomas Shean Yaw Choong⁴ and Bee Lin Chua¹

¹ School of Engineering, Taylor’s University, Lakeside Campus, No 1, Jalan Taylor’s, Subang Jaya, Selangor 47500, Malaysia

² School of Engineering and Physical Sciences, Heriot-Watt University, Malaysia Campus, No 1 Jalan Venna P5/2, Precinct 5, Putrajaya 62200, Malaysia

³ School of Biosciences, Taylor’s University, Lakeside Campus, No 1, Jalan Taylor’s, Subang Jaya, Selangor 47500, Malaysia

⁴ Department of Chemical and Environmental Engineering, University Putra Malaysia, UPM Serdang, Selangor 43400, Malaysia

Molecules 2018, 23(2), 484; https://doi.org/10.3390/molecules23020484 - 23 Feb 2018

Cited by 91 | Viewed by 6642

Abstract

The phenolic constituents in Piper betle are well known for their antioxidant potential; however, current literature has very little information on their stability under the influence of storage factors. Present study evaluated the stability of total phenolic content (TPC) and antioxidant activity together [...] Read more.

The phenolic constituents in Piper betle are well known for their antioxidant potential; however, current literature has very little information on their stability under the influence of storage factors. Present study evaluated the stability of total phenolic content (TPC) and antioxidant activity together with individual phenolic constituents (hydroxychavicol, eugenol, isoeugenol and allylpyrocatechol 3,4-diacetate) present in dried Piper betle’s extract under different storage temperature of 5 and 25 °C with and without light for a period of six months. Both light and temperature significantly influenced TPC and its corresponding antioxidant activity over time. More than 95% TPC and antioxidant activity was retained at 5 °C in dark condition after 180 days of storage. Hydroxychavicol demonstrated the best stability with no degradation while eugenol and isoeugenol displayed moderate stability in low temperature (5 °C) and dark conditions. 4-allyl-1,2-diacetoxybenzene was the only compound that underwent complete degradation. A new compound, 2,4-di-tert-butylphenol, was detected after five weeks of storage only in the extracts exposed to light. Both zero-order and first-order kinetic models were adopted to describe the degradation kinetics of the extract’s antioxidant activity. Zero-order displayed better fit with higher correlation coefficients (R² = 0.9046) and the half-life was determined as 62 days for the optimised storage conditions (5 °C in dark conditions). Full article

(This article belongs to the Section Natural Products Chemistry)

7 pages, 1046 KiB

Open AccessFeature PaperArticle

Epitaxially Grown Ultra-Flat Self-Assembling Monolayers with Dendrimers

by Takane Imaoka^1,2,3, Noriko Bukeo¹ and Kimihisa Yamamoto^1,2,*

¹ Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama 225-8503, Japan

² ERATO, Japan Science and Technology Agency, Chiyoda 102-0076, Japan

³ PRESTO, Japan Science and Technology Agency, Chiyoda 102-8666, Japan

Molecules 2018, 23(2), 485; https://doi.org/10.3390/molecules23020485 - 23 Feb 2018

Viewed by 3606

Abstract

Mono-molecular films formed by physical adsorption and dendrimer self-assembly were prepared on various substrate surfaces. It was demonstrated that a uniform dendrimer-based monolayer on the subnanometer scale can be easily constructed via simple dip coating. Furthermore, it was shown that an epitaxially grown [...] Read more.

Mono-molecular films formed by physical adsorption and dendrimer self-assembly were prepared on various substrate surfaces. It was demonstrated that a uniform dendrimer-based monolayer on the subnanometer scale can be easily constructed via simple dip coating. Furthermore, it was shown that an epitaxially grown monolayer film reflecting the crystal structure of the substrate (highly ordered pyrolytic graphite (HOPG)) can also be formed by aligning specific conditions. Full article

(This article belongs to the Special Issue Dendrimers: A Themed Issue in Honor of Professor Donald A. Tomalia on the Occasion of His 80th Birthday)

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16 pages, 7229 KiB

Open AccessArticle

Reconstructing Phylogeny by Aligning Multiple Metabolic Pathways Using Functional Module Mapping

by Yiran Huang^1,2,3,*, Cheng Zhong^1,4,*, Hai Xiang Lin⁵

, Jianyi Wang⁶ and Yuzhong Peng³

¹ School of Computer and Electronics and Information, Guangxi Universities Key Laboratory of Parallel and Distributed Computing, Guangxi University, Nanning 530004, China

² School of Computer Science and Engineering, South China University of Technology, Guangzhou 510006, China

³ Guangxi Colleges and Universities Key Laboratory of Data Science, Guangxi Teachers Education University, Nanning 530001, China

⁴ Guangdong Key Laboratory of Popular High Performance Computers, Shenzhen Key Laboratory of Service Computing and Applications, Shenzhen 518060, China

⁵ Faculty of Electrical Engineering, Mathematics and Computer Science, Delft University of Technology, Mekelweg 4, 2628 CD Delft, The Netherlands

⁶ School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China

Molecules 2018, 23(2), 486; https://doi.org/10.3390/molecules23020486 - 23 Feb 2018

Cited by 2 | Viewed by 4217

Abstract

Comparison of metabolic pathways provides a systematic way for understanding the evolutionary and phylogenetic relationships in systems biology. Although a number of phylogenetic methods have been developed, few efforts have been made to provide a unified phylogenetic framework that sufficiently reflects the metabolic [...] Read more.

Comparison of metabolic pathways provides a systematic way for understanding the evolutionary and phylogenetic relationships in systems biology. Although a number of phylogenetic methods have been developed, few efforts have been made to provide a unified phylogenetic framework that sufficiently reflects the metabolic features of organisms. In this paper, we propose a phylogenetic framework that characterizes the metabolic features of organisms by aligning multiple metabolic pathways using functional module mapping. Our method transforms the alignment of multiple metabolic pathways into constructing the union graph of pathways, builds mappings between functional modules of pathways in the union graph, and infers phylogenetic relationships among organisms based on module mappings. Experimental results show that the use of functional module mapping enables us to correctly categorize organisms into main categories with specific metabolic characteristics. Traditional genome-based phylogenetic methods can reconstruct phylogenetic relationships, whereas our method can offer in-depth metabolic analysis for phylogenetic reconstruction, which can add insights into traditional phyletic reconstruction. The results also demonstrate that our phylogenetic trees are closer to the classic classifications in comparison to existing classification methods using metabolic pathway data. Full article

(This article belongs to the Special Issue Selected Papers from the Second CCF Bioinformatics Conference (CBC 2017))

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9 pages, 430 KiB

Open AccessArticle

Fast and Simple Analytical Method for Direct Determination of Total Chlorine Content in Polyglycerol by ICP-MS

by Agata Jakóbik-Kolon^1,*, Andrzej Milewski¹, Piotr Dydo¹

, Magdalena Witczak² and Joanna Bok-Badura¹

¹ Faculty of Chemistry, Silesian University of Technology, Krzywoustego 6, 44-100 Gliwice, Poland

² Wood Technology Institute, Bioenergy Department, Winiarska 1, 60-654 Poznan, Poland

Molecules 2018, 23(2), 487; https://doi.org/10.3390/molecules23020487 - 23 Feb 2018

Cited by 6 | Viewed by 3854

Abstract

The fast and simple method for total chlorine determination in polyglycerols using low resolution inductively coupled plasma mass spectrometry (ICP-MS) without the need for additional equipment and time-consuming sample decomposition was evaluated. Linear calibration curve for ³⁵Cl isotope in the concentration range [...] Read more.

The fast and simple method for total chlorine determination in polyglycerols using low resolution inductively coupled plasma mass spectrometry (ICP-MS) without the need for additional equipment and time-consuming sample decomposition was evaluated. Linear calibration curve for ³⁵Cl isotope in the concentration range 20–800 µg/L was observed. Limits of detection and quantification equaled to 15 µg/L and 44 µg/L, respectively. This corresponds to possibility of detection 3 µg/g and determination 9 µg/g of chlorine in polyglycerol using studied conditions (0.5% matrix-polyglycerol samples diluted or dissolved with water to an overall concentration of 0.5%). Matrix effects as well as the effect of chlorine origin have been evaluated. The presence of 0.5% (m/m) of matrix species similar to polyglycerol (polyethylene glycol—PEG) did not influence the chlorine determination for PEGs with average molecular weights (MW) up to 2000 Da. Good precision and accuracy of the chlorine content determination was achieved regardless on its origin (inorganic/organic). High analyte recovery level and low relative standard deviation values were observed for real polyglycerol samples spiked with chloride. Additionally, the Combustion Ion Chromatography System was used as a reference method. The results confirmed high accuracy and precision of the tested method. Full article

(This article belongs to the Special Issue Green Analytical Chemistry)

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12 pages, 2342 KiB

Open AccessArticle

An Interaction of Rhamnolipids with Cu²⁺ Ions

by Jolanta Cieśla^*, Magdalena Koczańska

and Andrzej Bieganowski

Institute of Agrophysics, Polish Academy of Sciences, Doświadczalna 4, 20-290 Lublin, Poland

Molecules 2018, 23(2), 488; https://doi.org/10.3390/molecules23020488 - 23 Feb 2018

Cited by 15 | Viewed by 4013

Abstract

This study was focused on the description of interaction between Cu²⁺ ions and the 1:1 mono- and dirhamnolipid mixtures in the premicellar and aggregated state in water and 20 mM KCl solution at pH 5.5 and 6.0. The critical micelle concentration of [...] Read more.

This study was focused on the description of interaction between Cu²⁺ ions and the 1:1 mono- and dirhamnolipid mixtures in the premicellar and aggregated state in water and 20 mM KCl solution at pH 5.5 and 6.0. The critical micelle concentration of biosurfactants was determined conductometrically and by the pH measurements. Hydrodynamic diameter and electrophoretic mobility were determined in micellar solutions using dynamic light scattering and laser Doppler electrophoresis, respectively. The copper immobilization by rhamnolipids, methylglycinediacetic acid (MGDA), and ethylenediaminetetraacetic acid (EDTA) was estimated potentiometrically for the Cu²⁺ to chelating agent molar ratio from 16:100 to 200:100. The degree of ion binding and the complex stability constant were calculated at a 1:1 metal to chelant molar ratio. The aggregates of rhamnolipids (diameter of 43–89 nm) were negatively charged. Biosurfactants revealed the best chelating activities in premicellar solutions. For all chelants studied the degree of metal binding decreased with the increasing concentration of the systems. The presence of K⁺ lowered Cu²⁺ binding by rhamnolipids, but did not modify the complex stability significantly. Immobilization of Cu²⁺ by biosurfactants did not cause such an increase of acidification as that observed in MGDA and EDTA solutions. Rhamnolipids, even in the aggregated form, can be an alternative for the classic chelating agents. Full article

(This article belongs to the Section Nanochemistry)

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13 pages, 3320 KiB

Open AccessArticle

Fast Determination of Yttrium and Rare Earth Elements in Seawater by Inductively Coupled Plasma-Mass Spectrometry after Online Flow Injection Pretreatment

by Zuhao Zhu and Airong Zheng^*

College of Ocean and Earth Sciences, Xiamen University, Xiamen 361102, China

Molecules 2018, 23(2), 489; https://doi.org/10.3390/molecules23020489 - 23 Feb 2018

Cited by 29 | Viewed by 5148

Abstract

A method for daily monitoring of yttrium and rare earth elements (YREEs) in seawater using a cheap flow injection system online coupled to inductively coupled plasma-mass spectrometry is reported. Toyopearl AF Chelate 650M^® resin permits separation and concentration of YREEs using a [...] Read more.

A method for daily monitoring of yttrium and rare earth elements (YREEs) in seawater using a cheap flow injection system online coupled to inductively coupled plasma-mass spectrometry is reported. Toyopearl AF Chelate 650M^® resin permits separation and concentration of YREEs using a simple external calibration. A running cycle consumed 6 mL sample and took 5.3 min, providing a throughput of 11 samples per hour. Linear ranges were up to 200 ng kg⁻¹ except Tm (100 ng kg⁻¹). The precision of the method was <6% (RSDs, n = 5), and recoveries ranged from 93% to 106%. Limits of detection (LODs) were in the range 0.002 ng kg⁻¹ (Tm) to 0.078 ng kg⁻¹ (Ce). Good agreement between YREEs concentrations in CASS-4 and SLEW-3 obtained in this work and results from other studies was observed. The proposed method was applied to the determination of YREEs in seawater from the Jiulong River Estuary and the Taiwan Strait. Full article

(This article belongs to the Special Issue Innovative Extraction Techniques and Hyphenated Instrument Configuration for Complex Matrices Analysis)

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10 pages, 3168 KiB

Open AccessArticle

Structural Dynamics of DPP-4 and Its Influence on the Projection of Bioactive Ligands

by Simone Queiroz Pantaleão¹

, Eric Allison Philot², Pedro Túlio De Resende-Lara^1,3

, Angélica Nakagawa Lima¹, David Perahia³, Maria Atanassova Miteva⁴, Ana Ligia Scott^2,5 and Kathia Maria Honorio^1,6,*

¹ Center for Natural and Human Sciences, Federal University of ABC, 09210-170 Santo André, SP, Brazil

² Center for Mathematics, Computing, and Cognition, Federal University of ABC, 09210-170 Santo André, SP, Brazil

³ École Normale Supérieure Paris-Saclay, Laboratory of Biology and Applied Pharmacology, 94235 Cachan, France

⁴ Inserm UMR-S 973-Paris Diderot University, Therapeutic Molecules by in silico approaches, 75013 Paris, France

⁵ Department of Computational & Systems Biology School of Medicine, University of Pittsburgh, 15260 Pittsburgh, PA, USA

⁶ School of Arts, Sciences and Humanities, University of Sao Paulo, 03828-0000 Sao Paulo, SP, Brazil

Molecules 2018, 23(2), 490; https://doi.org/10.3390/molecules23020490 - 23 Feb 2018

Cited by 28 | Viewed by 8712

Abstract

Dipeptidyl peptidase-4 (DPP-4) is a target to treat type II diabetes mellitus. Therefore, it is important to understand the structural aspects of this enzyme and its interaction with drug candidates. This study involved molecular dynamics simulations, normal mode analysis, binding site detection and [...] Read more.

Dipeptidyl peptidase-4 (DPP-4) is a target to treat type II diabetes mellitus. Therefore, it is important to understand the structural aspects of this enzyme and its interaction with drug candidates. This study involved molecular dynamics simulations, normal mode analysis, binding site detection and analysis of molecular interactions to understand the protein dynamics. We identified some DPP-4 functional motions contributing to the exposure of the binding sites and twist movements revealing how the two enzyme chains are interconnected in their bioactive form, which are defined as chains A (residues 40–767) and B (residues 40–767). By understanding the enzyme structure, its motions and the regions of its binding sites, it will be possible to contribute to the design of new DPP-4 inhibitors as drug candidates to treat diabetes. Full article

(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)

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11 pages, 902 KiB

Open AccessArticle

Triterpenoid Saponins from Anemone rivularis var. Flore-Minore and Their Anti-Proliferative Activity on HSC-T6 Cells

by Xiao-Yang Wang^1,†, Hui Gao^2,†, Xiao-Jie Xie¹, Jirimubatu Jurhiin³, Mu-Zi-He Zhang¹, Yan-Ping Zhou¹, Rui Liu¹, Meng Ning¹, Jin Han^1,* and Hai-Feng Tang^4,*

¹ Department of Pharmacy, People’s Liberation Army Institute of Chinese Medicine, Beijing 100039, China

² People's Liberation Army Institute of Organ Transplantation, Beijing 100091, China

³ Academy of Mongolian Medicine, Inner Mongolia Medical University, Hohhot 010110, China

⁴ Institute of Materia Medica, School of Pharmacy, The Fourth Military Medical University, Xi’an 710032, China

^† The authors contribute equally to this work.

Molecules 2018, 23(2), 491; https://doi.org/10.3390/molecules23020491 - 23 Feb 2018

Cited by 4 | Viewed by 4160

Abstract

Five previously undescribed triterpenoid saponins (1–5), along with eight known ones (6–13), were isolated from the whole plants of Anemone rivularis var. flore-minore. Their structures were clarified by extensive spectroscopic data and chemical evidence. [...] Read more.

Five previously undescribed triterpenoid saponins (1–5), along with eight known ones (6–13), were isolated from the whole plants of Anemone rivularis var. flore-minore. Their structures were clarified by extensive spectroscopic data and chemical evidence. For the first time, the lupane-type saponins (3 and 12) were reported from the Anemone genus. The anti-proliferative activity of all isolated saponins was evaluated on hepatic stellate cells (HSC-T6). Saponins 12 and 13, which possess more monosaccharides than the others, displayed potent anti-proliferative activity, with IC₅₀ values of 18.21 and 15.56 μM, respectively. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 3201 KiB

Open AccessArticle

Melatonin-Mediated Development of Ovine Cumulus Cells, Perhaps by Regulation of DNA Methylation

by Yi Fang^1,2,†, Shoulong Deng^3,†, Jinlong Zhang¹, Haijun Liu¹, Yihai Li¹, Xiaosheng Zhang^1,* and Yixun Liu^3,*

¹ Animal Husbandry and Veterinary Research Institute of Tianjin, Tianjin 300381, China

² Jilin Provincial Key Laboratory of Grassland Farming, Northeast Institute of Geography and Agoecology, Chinese Academy of Sciences, Changchun, Jilin 130062, China

³ State Key Laboratory of Stem Cell and Reproduction Biology, Institute of Zoology, Chinese Academy of Science, Beijing 100101, China

^† These authors contributed equally to this paper.

Molecules 2018, 23(2), 494; https://doi.org/10.3390/molecules23020494 - 23 Feb 2018

Cited by 17 | Viewed by 4875

Abstract

Cumulus cells of pre-pubertal domestic animals are dysfunctional, perhaps due to age-specific epigenetic events. This study was designed to determine effects of melatonin treatment of donors on methylation modification of pre-pubertal cumulus cells. Cumulus cells from germinal vesicle stage cumulus oocyte complexes (COCs) [...] Read more.

Cumulus cells of pre-pubertal domestic animals are dysfunctional, perhaps due to age-specific epigenetic events. This study was designed to determine effects of melatonin treatment of donors on methylation modification of pre-pubertal cumulus cells. Cumulus cells from germinal vesicle stage cumulus oocyte complexes (COCs) were collected from eighteen lambs which were randomly divided into control group (C) and melatonin group given an 18 mg melatonin implant subcutaneous (M). Compared to the C group, the M group had higher concentrations of melatonin in plasma and follicular fluid (p < 0.05), greater superovulation, a higher proportion of fully expanded COCs, and a lower proportion of apoptotic cumulus cells (p < 0.05). Real-time PCR results showed that melatonin up-regulated expression of genes MT1, Bcl2, DNMT1, DNMT3a and DNMT3b, but down-regulated expression of genes p53, Caspase 3 and Bax (p < 0.05). Furthermore, melatonin increased FI of FITC (global methylation level) on cumulus cells (p < 0.05). To understand the regulation mechanism, the DNMTs promoter methylation sequence were analyzed. Compared to the C group, although there was less methylation at two CpG sites of DNMT1 (p < 0.05) and higher methylation at two CpG sites of DNMT3a (p < 0.05), there were no significant differences in methylation of the detected DNMT1 and DNMT3a promoter regions. However, there were lower methylation levels at five CpG sites of DNMT3b, which decreased methylation of detected DNMT3b promoter region on M group (p < 0.05). In conclusion, alterations of methylation regulated by melatonin may mediate development of cumulus cells in lambs. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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13 pages, 3627 KiB

Open AccessArticle

Physicochemical Properties and Chemical Stability of β-Carotene Bilayer Emulsion Coated with Bovine Serum Albumin and Arabic Gum Compared to Monolayer Emulsions

by Bulei Sheng¹, Lin Li^1,2,3, Xia Zhang^1,2,*, Wenjuan Jiao¹, Di Zhao¹, Xue Wang¹, Liting Wan¹, Bing Li^1,2,* and Hui Rong⁴

¹ College of Food Science and Engineering, South China University of Technology, 381 Wushan Road, Guangzhou 510640, China

² Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, 381 Wushan Road, Guangzhou 510640, China

³ School of Chemical Engineering and Energy Technology, Dongguan University of Technology, College Road 1, Dongguan 523808, China

⁴ Guangzhou Entry-Exit Inspection & Quarantine Bureau of China, Guangzhou 510623, China

Molecules 2018, 23(2), 495; https://doi.org/10.3390/molecules23020495 - 23 Feb 2018

Cited by 26 | Viewed by 7408

Abstract

β-carotene is a lipophilic micronutrient that is considered beneficial to human health. However, there are some limitations in utilizing β-carotene in functional foods or dietary supplements currently because of its poor water dispersibility and chemical stability. A new type of β-carotene bilayer emulsion [...] Read more.

β-carotene is a lipophilic micronutrient that is considered beneficial to human health. However, there are some limitations in utilizing β-carotene in functional foods or dietary supplements currently because of its poor water dispersibility and chemical stability. A new type of β-carotene bilayer emulsion delivery system was prepared by a layer-by-layer electrostatic deposition technique, for which were chosen bovine serum albumin (BSA) as the inner emulsifier and Arabic gum (GA) as the outer emulsifier. The physicochemical properties of bilayer emulsions were mainly characterized by droplet size distribution, zeta potential, rheological behavior, Creaming Index (CI), and encapsulation ratio of β-carotene. Besides this, the effects of processing conditions (pH, thermal treatment, UV radiation, strong oxidant) and storage time on the chemical stability of bilayer emulsions were also evaluated. The bilayer emulsion had a small droplet size (221.27 ± 5.17 nm) and distribution (PDI = 0.23 ± 0.02), strong zeta potential (−30.37 ± 0.71 mV), good rheological behavior (with the highest viscosity that could reduce the possibility of flocculation) and physical stability (CI = 0), high β-carotene encapsulation ratio (94.35 ± 0.71%), and low interfacial tension (40.81 ± 0.86 mN/m). It also obtained better chemical stability under different environmental stresses when compared with monolayer emulsions studied, because it had a dense and thick bilayer structure. Full article

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16 pages, 5502 KiB

Open AccessArticle

In Silico-Based Repositioning of Phosphinothricin as a Novel Technetium-99m Imaging Probe with Potential Anti-Cancer Activity

by Tamer M. Sakr^1,2

, Mohammed A. Khedr^3,4,*, Hassan M. Rashed⁵ and Maged E. Mohamed^4,6

¹ Radioactive Isotopes and Generator Department, Hot Labs Center, Atomic Energy Authority, Cairo 13759, Egypt

² Pharmaceutical Chemistry Department, Faculty of Pharmacy, October University of Modern Sciences and Arts (MSA), Giza 12111, Egypt

³ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Ein Helwan, Cairo 11795, Egypt

⁴ College of Clinical Pharmacy, King Faisal University, Al-Hasaa 31982, Kingdom of Saudi Arabia

⁵ Labeled Compounds Department, Hot Labs Center, Atomic Energy Authority, Cairo 13759, Egypt

⁶ Department of Pharmacognosy, Faculty of Pharmacy, University of Zagazig, Zagazig 44519, Egypt

Molecules 2018, 23(2), 496; https://doi.org/10.3390/molecules23020496 - 23 Feb 2018

Cited by 26 | Viewed by 5430

Abstract

l-Phosphinothricin (glufosinate or 2-amino-4-((hydroxy(methyl) phosphinyl) butyric acid ammonium salt (AHPB)), which is a structural analog of glutamate, is a recognized herbicide that acts on weeds through inhibition of glutamine synthetase. Due to the structural similarity between phosphinothricin and some bisphosphonates (BPs), this [...] Read more.

l-Phosphinothricin (glufosinate or 2-amino-4-((hydroxy(methyl) phosphinyl) butyric acid ammonium salt (AHPB)), which is a structural analog of glutamate, is a recognized herbicide that acts on weeds through inhibition of glutamine synthetase. Due to the structural similarity between phosphinothricin and some bisphosphonates (BPs), this study focuses on investigating the possibility of repurposing phosphinothricin as a bisphosphonate analogue, particularly in two medicine-related activities: image probing and as an anti-cancer drug. As BP is a competitive inhibitor of human farnesyl pyrophosphate synthase (HFPPS), in silico molecular docking and dynamic simulations studies were established to evaluate the binding and stability of phosphinothricin with HFPPS, while the results showed good binding and stability in the active site of the enzyme in relation to alendronate. For the purpose of inspecting bone-tissue accumulation of phosphinothricin, a technetium (^99mTc)–phosphinothricin complex was developed and its stability and tissue distribution were scrutinized. The radioactive complex showed rapid, high and sustained uptake into bone tissues. Finally, the cytotoxic activity of phosphinothricin was tested against breast and lung cancer cells, with the results indicating cytotoxic activity in relation to alendronate. All the above results provide support for the use of phosphinothricin as a potential anti-cancer drug and of its technetium complex as an imaging probe. Full article

(This article belongs to the Special Issue Molecular Imaging and Treatment Monitoring of Cancer)

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14 pages, 3343 KiB

Open AccessArticle

Characterization, Stability and Biological Activity In Vitro of Cathelicidin-BF-30 Loaded 4-Arm Star-Shaped PEG-PLGA Microspheres

by Yueli Bao^1,†, Shanrong Wang^2,†, Hongli Li¹, Yunjiao Wang¹, Haiyun Chen^1,* and Minglong Yuan^1,*

¹ Engineering Research Center of Biopolymer Functional Materials of Yunnan, Yunnan Minzu University, Kunming 650500, China

² Yunnan Rural Leader College, Yunnan Agricultural University, Heilongtan, Kunming 650201, China

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 497; https://doi.org/10.3390/molecules23020497 - 23 Feb 2018

Cited by 15 | Viewed by 4892

Abstract

BF-30 is a single chain polypeptide of an N-segment with an α-helix from cathelicidin gene encoding, and it contains 30 amino acid residues, with a relative molecular mass and isoelectric point of 3637.54 and 11.79, respectively. Cathelicidin-BF-30 was entrapped in four-arm star-shaped poly(ethylene [...] Read more.

BF-30 is a single chain polypeptide of an N-segment with an α-helix from cathelicidin gene encoding, and it contains 30 amino acid residues, with a relative molecular mass and isoelectric point of 3637.54 and 11.79, respectively. Cathelicidin-BF-30 was entrapped in four-arm star-shaped poly(ethylene glycol-b-dl-lactic acid-co-glycolic acid) block copolymers (4-arm-PEG-PLGA) by a double-emulsion solvent-evaporation method. Three release phases of cathelicidin-BF-30loaded 4-arm-PEG-PLGA microspheres were observed, including an initial burst-release phase, followed by a lag phase with minimal drug release and finally a secondary zero-order release phase. The delivery system released BF-30 over more than 15 days in vitro. Furthermore, the material for preparing the microspheres has good biocompatibility and biodegradability. Additionally, based on the drug resistance of food pathogenic bacteria, the antibacterial effects of BF-30 on Shigella dysenteriae CMCC 51105 (Sh. dysenteriae CMCC 51105), Salmonella typhi (S. typhi) and Staphylococcus aureus (S. aureus) as well as the stability of the in vitro release of the BF-30-loded microspheres were studied. The α-helix secondary structure and antibacterial activity of released BF-30 were retained and compared with native peptide. These BF-30 loaded microspheres presented <10% hemolysis and no toxicity for HEK293T cells even at the highest tested concentration (150 μg/mL), indicating that they are hemocompatible and a promising delivery and protection system for BF-30 peptide. Full article

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13 pages, 3030 KiB

Open AccessArticle

Antioxidation and Cytoprotection of Acteoside and Its Derivatives: Comparison and Mechanistic Chemistry

by Xican Li^1,2,*,†

, Yulu Xie^1,2,†, Ke Li^3,4, Aizhi Wu^1,2,*, Hong Xie^1,2, Qian Guo^1,5, Penghui Xue¹, Yerkingul Maleshibek¹, Wei Zhao⁶, Jiasong Guo⁷ and Dongfeng Chen^3,4

¹ School of Chinese Herbal Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

² Innovative Research & Development Laboratory of TCM, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

³ School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

⁴ The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

⁵ School of Basic Medical Science, Guangdong Pharmaceutical University, Guangzhou 510007, China

⁶ Zhongshan School of Medicine, Sun Yat-sen University, No. 74 Zhongshan Road. 2, Guangzhou 510080, China

⁷ Department of Histology and Embryology, Southern Medical University, Guangzhou 510515, China

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 498; https://doi.org/10.3390/molecules23020498 - 23 Feb 2018

Cited by 29 | Viewed by 4921

Abstract

The study tried to explore the role of sugar-residues and mechanisms of phenolic phenylpropanoid antioxidants. Acteoside, along with its apioside forsythoside B and rhamnoside poliumoside, were comparatively investigated using various antioxidant assays. In three electron-transfer (ET)-based assays (FRAP, CUPRAC, PTIO•-scavenging at pH 4.5), [...] Read more.

The study tried to explore the role of sugar-residues and mechanisms of phenolic phenylpropanoid antioxidants. Acteoside, along with its apioside forsythoside B and rhamnoside poliumoside, were comparatively investigated using various antioxidant assays. In three electron-transfer (ET)-based assays (FRAP, CUPRAC, PTIO•-scavenging at pH 4.5), the relative antioxidant levels roughly ruled as: acteoside >forsythoside B > poliumoside. Such order was also observed in H⁺-transfer-involved PTIO•-scavenging assay at pH 7.4, and in three multiple-pathway-involved radical-scavenging assays, i.e., ABTS⁺•-scavenging, DPPH•-scavenging, and •O₂⁻-scavenging. In UV-vis spectra, each of them displayed a red-shift at 335→364 nm and two weak peaks (480 and 719 nm), when mixed with Fe²⁺; however, acteoside gave the weakest absorption. In Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC−ESI−Q−TOF−MS/MS) analysis, no radical-adduct-formation (RAF) peak was found. MTT assay revealed that poliumoside exhibited the highest viability of oxidative-stressed bone marrow-derived mesenchymal stem cells. In conclusion, acteoside, forsythoside B, and poliumoside may be involved in multiple-pathways to exert the antioxidant action, including ET, H⁺-transfer, or Fe²⁺-chelating, but not RAF. The ET and H⁺-transfer may be hindered by rhamnosyl and apiosyl moieties; however, the Fe²⁺-chelating potential can be enhanced by two sugar-residues (especially rhamnosyl moiety). The general effect of rhamnosyl and apiosyl moieties is to improve the antioxidant or cytoprotective effects. Full article

(This article belongs to the Special Issue The Antioxidant Capacities of Natural Products)

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18 pages, 3901 KiB

Open AccessArticle

Establishment of the Volatile Signature of Wine-Based Aromatic Vinegars Subjected to Maceration

by Rosa Perestrelo¹, Catarina L. Silva¹, Pedro Silva¹

and José S. Câmara^1,2,*

¹ CQM—Centro de Química da Madeira, Universidade da Madeira, Campus da Penteada, 9020-105 Funchal, Portugal

² Departamento de Química, Faculdade de Ciências Exatas e Engenharia, Universidade da Madeira, Campus da Penteada, 9020-105 Funchal, Portugal

Molecules 2018, 23(2), 499; https://doi.org/10.3390/molecules23020499 - 23 Feb 2018

Cited by 14 | Viewed by 5356

Abstract

The flavoring of vinegars with aromatic fruits and medicinal herbs is a practice with increasing trend mostly in countries with oenological tradition, resulting in a product of improved quality and consumer attractiveness. This study was directed towards the evaluation of the impact of [...] Read more.

The flavoring of vinegars with aromatic fruits and medicinal herbs is a practice with increasing trend mostly in countries with oenological tradition, resulting in a product of improved quality and consumer attractiveness. This study was directed towards the evaluation of the impact of the maceration process on the volatile signature of wine-based aromatic vinegars (WBAVs). The evaluation was performed using solid phase microextraction (SPME) combined with gas chromatography combined with mass spectrometry (GC-MS). Experimental parameters influencing headspace solid (HS)-SPME extraction efficiency, were optimized using an univariate experimental design. The best results were achieved using a polydimethylsiloxane (PDMS) fiber, 10 mL of vinegar sample, at 50 °C for 30 min of extraction. This way One hundred and three volatile organic compounds (VOCs), belonging to different chemical families including ethyl esters (37), higher alcohols (20), fatty acids (10), terpenoids (23), carbonyl compounds (six), lactones (five) and volatile phenols (two), were identified in wine vinegar (control) and WBAV. As far as we know, 34 of these VOCs are reported for the first time in macerated vinegars. Higher alcohols and lactones are the major chemical families in WBAV macerated with apple, whereas terpenoids are predominant in WBAV macerated with banana. The obtained data represent a suitable tool to guarantee the authenticity and genuineness of WBAV, as well as to promote the production of WBAV with improved sensorial and organoleptic properties. To the best of our knowledge, there are no reported studies dealing with the volatile signature of WBAV enriched with banana, passion fruit, apple and pennyroyal. Full article

(This article belongs to the Section Analytical Chemistry)

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16 pages, 2808 KiB

Open AccessArticle

Graphene Oxide as a Nanocarrier for a Theranostics Delivery System of Protocatechuic Acid and Gadolinium/Gold Nanoparticles

by Muhammad Sani Usman^1,*, Mohd Zobir Hussein^1,*

, Aminu Umar Kura², Sharida Fakurazi³, Mas Jaffri Masarudin⁴

and Fathinul Fikri Ahmad Saad⁵

¹ Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia

² Pharmacology, Faculty of Basic Health Sciences, Bauchi State University, Bauchi 65, Nigeria

³ Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia

⁴ Department of Cell & Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia

⁵ Centre for Diagnostic and Nuclear Imaging, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia

Molecules 2018, 23(2), 500; https://doi.org/10.3390/molecules23020500 - 24 Feb 2018

Cited by 33 | Viewed by 5158

Abstract

We have synthesized a graphene oxide (GO)-based theranostic nanodelivery system (GOTS) for magnetic resonance imaging (MRI) using naturally occurring protocatechuic acid (PA) as an anticancer agent and gadolinium (III) nitrate hexahydrate (Gd) as the starting material for a contrast agent,. Gold nanoparticles (AuNPs) [...] Read more.

We have synthesized a graphene oxide (GO)-based theranostic nanodelivery system (GOTS) for magnetic resonance imaging (MRI) using naturally occurring protocatechuic acid (PA) as an anticancer agent and gadolinium (III) nitrate hexahydrate (Gd) as the starting material for a contrast agent,. Gold nanoparticles (AuNPs) were subsequently used as second diagnostic agent. The GO nanosheets were first prepared from graphite via the improved Hummer’s protocol. The conjugation of the GO and the PA was done via hydrogen bonding and π–π stacking interactions, followed by surface adsorption of the AuNPs through electrostatic interactions. GAGPA is the name given to the nanocomposite obtained from Gd and PA conjugation. However, after coating with AuNPs, the name was modified to GAGPAu. The physicochemical properties of the GAGPA and GAGPAu nanohybrids were studied using various characterization techniques. The results from the analyses confirmed the formation of the GOTS. The powder X-ray diffraction (PXRD) results showed the diffractive patterns for pure GO nanolayers, which changed after subsequent conjugation of the Gd and PA. The AuNPs patterns were also recorded after surface adsorption. Cytotoxicity and magnetic resonance imaging (MRI) contrast tests were also carried out on the developed GOTS. The GAGPAu was significantly cytotoxic to the human liver hepatocellular carcinoma cell line (HepG2) but nontoxic to the standard fibroblast cell line (3T3). The GAGPAu also appeared to possess higher T1 contrast compared to the pure Gd and water reference. The GOTS has good prospects of serving as future theranostic platform for cancer chemotherapy and diagnosis. Full article

(This article belongs to the Section Nanochemistry)

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24 pages, 3796 KiB

Open AccessArticle

Kinetics and Optimization of Lipophilic Kojic Acid Derivative Synthesis in Polar Aprotic Solvent Using Lipozyme RMIM and Its Rheological Study

by Nurazwa Ishak^1,†, Ahmad Firdaus B. Lajis^1,2,†

, Rosfarizan Mohamad¹

, Arbakariya B. Ariff^1,2, Mohd Shamzi Mohamed^1,2

, Murni Halim^1,2 and Helmi Wasoh^1,2,*

¹ Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

² Bioprocessing and Biomanufacturing Research Centre, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 501; https://doi.org/10.3390/molecules23020501 - 24 Feb 2018

Cited by 16 | Viewed by 6059

Abstract

The synthesis of kojic acid derivative (KAD) from kojic and palmitic acid (C16:0) in the presence of immobilized lipase from Rhizomucor miehei (commercially known as Lipozyme RMIM), was studied using a shake flask system. Kojic acid is a polyfunctional heterocycles that acts as [...] Read more.

The synthesis of kojic acid derivative (KAD) from kojic and palmitic acid (C16:0) in the presence of immobilized lipase from Rhizomucor miehei (commercially known as Lipozyme RMIM), was studied using a shake flask system. Kojic acid is a polyfunctional heterocycles that acts as a source of nucleophile in this reaction allowing the formation of a lipophilic KAD. In this study, the source of biocatalyst, Lipozyme RMIM, was derived from the lipase of Rhizomucor miehei immobilized on weak anion exchange macro-porous Duolite ES 562 by the adsorption technique. The effects of solvents, enzyme loading, reaction temperature, and substrate molar ratio on the reaction rate were investigated. In one-factor-at-a-time (OFAT) experiments, a high reaction rate (30.6 × 10⁻³ M·min⁻¹) of KAD synthesis was recorded using acetone, enzyme loading of 1.25% (w/v), reaction time of 12 h, temperature of 50 °C and substrate molar ratio of 5:1. Thereafter, a yield of KAD synthesis was optimized via the response surface methodology (RSM) whereby the optimized molar ratio (fatty acid: kojic acid), enzyme loading, reaction temperature and reaction time were 6.74, 1.97% (w/v), 45.9 °C, and 20 h respectively, giving a high yield of KAD (64.47%). This condition was reevaluated in a 0.5 L stirred tank reactor (STR) where the agitation effects of two impellers; Rushton turbine (RT) and pitch-blade turbine (PBT), were investigated. In the STR, a very high yield of KAD synthesis (84.12%) was achieved using RT at 250 rpm, which was higher than the shake flask, thus indicating better mixing quality in STR. In a rheological study, a pseudoplastic behavior of KAD mixture was proposed for potential application in lotion formulation. Full article

(This article belongs to the Special Issue Lipases and Lipases Modification)

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9 pages, 4396 KiB

Open AccessArticle

Pilot Study of ⁶⁴CuCl₂ for PET Imaging of Inflammation

by Lei Jiang^1,2, Dongli Song³, Hao Chen², Ao Zhang⁴

, Huoqiang Wang^1,* and Zhen Cheng^2,*

¹ Department of Nuclear Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China

² Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA 94305-5484, USA

³ Institute of Clinical Science, Zhongshan Hospital, Fudan University, Shanghai 200032, China

⁴ CAS Key Laboratory of Receptor Research, Synthetic Organic & Medicinal Chemistry Laboratory (SOMCL), Shanghai Institute of Materia Medica, Chinese Academy of Sciences, No. 555 Zuchong Road, Pudong New Area, Shanghai 201203, China

Molecules 2018, 23(2), 502; https://doi.org/10.3390/molecules23020502 - 24 Feb 2018

Cited by 9 | Viewed by 5113

Abstract

Copper(II) ion (Cu²⁺) is the essential element for numerous pathophysiological processes in vivo. Copper transporter 1 (CTR1) is mainly responsible for maintaining Cu²⁺ accumulation in cells, which has been found to be over-expressed in inflammatory tissues. Therefore, we explored the [...] Read more.

Copper(II) ion (Cu²⁺) is the essential element for numerous pathophysiological processes in vivo. Copper transporter 1 (CTR1) is mainly responsible for maintaining Cu²⁺ accumulation in cells, which has been found to be over-expressed in inflammatory tissues. Therefore, we explored the potential application of ⁶⁴CuCl₂ for PET imaging of inflammation through targeting CTR1. The animal models of H₂O₂ induced muscle inflammation and lipopolysaccaharide induced lung inflammation were successfully established, then imaged by small animal PET (PET/CT) post-injection of ⁶⁴CuCl₂, and PET images were quantitatively analyzed. H&E and immunohistochemical (IHC) staining and western blot experiments were performed for evaluating CTR1 levels in the inflammatory and control tissues. Both inflammatory muscle and lungs can be clearly imaged by PET. PET image quantitative analysis revealed that the inflammatory muscle and lungs showed significantly higher ⁶⁴Cu accumulation than the controls, respectively (p < 0.05). Furthermore, IHC staining and western blot analysis demonstrated that compared with the controls, CTR1 expression was increased in both the inflammatory muscle and lungs, which was consistent with the levels of ⁶⁴Cu²⁺ accumulation in these tissues. ⁶⁴CuCl₂ can be used as a novel, simple, and highly promising PET tracer for CTR1 targeted imaging of inflammation. Full article

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12 pages, 783 KiB

Open AccessCommunication

Bacillus Cellulase Molecular Cloning, Expression, and Surface Display on the Outer Membrane of Escherichia coli

by Daehwan Kim^1,2

and Seockmo Ku^3,*

¹ Laboratory of Renewable Resources Engineering, Purdue University, West Lafayette, IN 47907, USA

² Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA

³ Fermentation Science Program, School of Agribusiness and Agriscience, College of Basic and Applied Sciences, Middle Tennessee State University, Murfreesboro, TN 37132, USA

Molecules 2018, 23(2), 503; https://doi.org/10.3390/molecules23020503 - 24 Feb 2018

Cited by 25 | Viewed by 6632

Abstract

One of the main challenges of using recombinant enzymes is that they are derived from genetically-modified microorganisms commonly located in the intracellular region. The use of these recombinant enzymes for commercial purposes requires the additional processes of cell disruption and purification, which may [...] Read more.

One of the main challenges of using recombinant enzymes is that they are derived from genetically-modified microorganisms commonly located in the intracellular region. The use of these recombinant enzymes for commercial purposes requires the additional processes of cell disruption and purification, which may result in enzyme loss, denaturation, and increased total production cost. In this study, the cellulase gene of Bacillus licheniformis ATCC 14580 was cloned, over-expressed, and surface displayed in recombinant Escherichia coli using an ice-nucleation protein (INP). INP, an outer membrane-bound protein from Pseudomonas syringae, was utilized as an anchor linker, which was cloned with a foreign cellulase gene into the pET21a vector to develop a surface display system on the outer membrane of E. coli. The resulting strain successfully revealed cellulase on the host cell surface. The over-expressed INP-cellulase fusion protein was confirmed via staining assay for determining the extracellular cellulase and Western blotting method for the molecular weight (MW) of cellulase, which was estimated to be around 61.7 kDa. Cell fractionation and localization tests demonstrated that the INP-cellulase fusion protein was mostly present in the supernatant (47.5%) and outer membrane (19.4%), while the wild-type strain intracellularly retained enzymes within cytosol (>61%), indicating that the INP gene directed the cellulase expression on the bacteria cell surface. Further studies of the optimal enzyme activity were observed at 60 °C and pH 7.0, and at least 75% of maximal enzyme activity was preserved at 70 °C. Full article

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11 pages, 1211 KiB

Open AccessArticle

Discovery of Flavonoids from Scutellaria baicalensis with Inhibitory Activity Against PCSK 9 Expression: Isolation, Synthesis and Their Biological Evaluation

by Piseth Nhoek, Hee-Sung Chae, Jagadeesh Nagarajappa Masagalli, Karabasappa Mailar, Pisey Pel

, Young-Mi Kim, Won Jun Choi^* and Young-Won Chin^*

¹ College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, 32 Dongguk-lo, Ilsandong-gu, Goyang-si, Gyeonggi-do 10326, Korea

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 504; https://doi.org/10.3390/molecules23020504 - 24 Feb 2018

Cited by 24 | Viewed by 4746

Abstract

Nine flavonoids were isolated and identified from a chloroform-soluble fraction of the roots of Scutellaria baicalensis through a bioactivity-guided fractionation using a proprotein convertase subtilisin/kexin type 9 (PCSK9) monitoring assay in HepG2 cells. All structures were established by interpreting the corresponding spectroscopic data [...] Read more.

Nine flavonoids were isolated and identified from a chloroform-soluble fraction of the roots of Scutellaria baicalensis through a bioactivity-guided fractionation using a proprotein convertase subtilisin/kexin type 9 (PCSK9) monitoring assay in HepG2 cells. All structures were established by interpreting the corresponding spectroscopic data and comparing measured values from those in the literature. All compounds were assessed for their ability to inhibit PCSK9 mRNA expression; compounds 1 (3,7,2′-trihydroxy-5-methoxy-flavanone) and 4 (skullcapflavone II) were found to suppress PCSK9 mRNA via SREBP-1. Furthermore, compound 1 was found to increase low-density lipoprotein receptor protein expression. Also, synthesis of compound 1 as a racemic mixture form (1a) was completed for the first time. Natural compound 1 and synthetic racemic 1a were evaluated for their inhibitory activities against PCSK9 mRNA expression and the results confirmed the stereochemistry of 1 was important. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 1690 KiB

Open AccessArticle

Separation of Seven Polyphenols from the Rhizome of Smilax glabra by Offline Two Dimension Recycling HSCCC with Extrusion Mode

by Wei Guo^1,2,3,4, Hongjing Dong⁵, Daijie Wang⁵, Bin Yang², Xiao Wang^5,*

and Luqi Huang^3,*

¹ School of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, 4655 Daxue Road, Jinan 250355, China

² Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China

³ State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, 16 Nanxiaojie, Beijing 100700, China

⁴ Shandong Academy of Chinese Medicine, 7 Yanzishanxi Street, Jinan 250014, China

⁵ Shandong Key Laboratory of TCM Quality Control Technology, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), 19 Keyuan Street, Jinan 250014, China

Molecules 2018, 23(2), 505; https://doi.org/10.3390/molecules23020505 - 24 Feb 2018

Cited by 12 | Viewed by 4769

Abstract

An offline two-dimensional recycling high-speed countercurrent chromatography (2D R-HSCCC) strategy with extrusion mode was developed for isolating polyphenols from the rhizome of Smilax glabra. Firstly, the ethyl acetate extract was divided into two fractions, Fr.1 and Fr.2, by silica gel column chromatography. [...] Read more.

An offline two-dimensional recycling high-speed countercurrent chromatography (2D R-HSCCC) strategy with extrusion mode was developed for isolating polyphenols from the rhizome of Smilax glabra. Firstly, the ethyl acetate extract was divided into two fractions, Fr.1 and Fr.2, by silica gel column chromatography. Then, HSCCC was applied to separate polyphenols from the two fractions using a solvent system consisting of petroleum ether–ethyl acetate–methanol–water (1:3:0.5:5, v/v). Fifty milligrams of Fr.1 was separated by conventional HSCCC, yielding 5-O-caffeoylshikimic acid (1, 15.8 mg) and taxifolin (2, 4.8 mg). Offline 2D R-HSCCC with extrusion mode was used to separate Fr.2, and astilbin (4, 37.3 mg), neoisoastilbin (5, 8.8 mg), engeletin (7, 7.9 mg), and a mixture of two polyphenols were obtained from 100 mg of Fr.2. The mixture of two polyphenols was further separated by pre-HPLC, yielding neoastilbin (3, 15.2 mg) and isoastilbin (6, 9.9 mg). The purities of these seven compounds were all over 96.0%. Their structures were identified by MS and NMR. The results demonstrated that the strategy based on offline 2D R-HSCCC with extrusion mode was a powerful tool to separate the main compounds from the rhizome of Smilax glabra and valued for the preparative separation compounds with broad K-values and similar structures. Full article

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14 pages, 2265 KiB

Open AccessArticle

Triterpene Acids from Frankincense and Semi-Synthetic Derivatives That Inhibit 5-Lipoxygenase and Cathepsin G

by Andreas Koeberle¹

, Arne Henkel², Moritz Verhoff², Lars Tausch³, Stefanie König¹, Dagmar Fischer⁴, Nicole Kather⁵, Stefanie Seitz⁵, Michael Paul⁵, Johann Jauch⁵ and Oliver Werz^1,*

¹ Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University, Philosophenweg 14, D-07743 Jena, Germany

² Department of Pharmaceutical Analytics, Pharmaceutical Institute, Eberhard Karls University, Auf der Morgenstelle 8, D-72076 Tuebingen, Germany

³ Institute of Pharmaceutical Chemistry, University of Frankfurt, Max-von-Laue-Str. 9, D-60438 Frankfurt, Germany

⁴ Department of Pharmaceutical Technology, Institute of Pharmacy, Friedrich-Schiller-University, Otto-Schott-Strasse 41, D-07745 Jena, Germany

⁵ Organic Chemistry II, Saarland University, Campus C4.2, D-66123 Saarbruecken, Germany

Molecules 2018, 23(2), 506; https://doi.org/10.3390/molecules23020506 - 24 Feb 2018

Cited by 17 | Viewed by 7154

Abstract

Age-related diseases, such as osteoarthritis, Alzheimer’s disease, diabetes, and cardiovascular disease, are often associated with chronic unresolved inflammation. Neutrophils play central roles in this process by releasing tissue-degenerative proteases, such as cathepsin G, as well as pro-inflammatory leukotrienes produced by the 5-lipoxygenase (5-LO) [...] Read more.

Age-related diseases, such as osteoarthritis, Alzheimer’s disease, diabetes, and cardiovascular disease, are often associated with chronic unresolved inflammation. Neutrophils play central roles in this process by releasing tissue-degenerative proteases, such as cathepsin G, as well as pro-inflammatory leukotrienes produced by the 5-lipoxygenase (5-LO) pathway. Boswellic acids (BAs) are pentacyclic triterpene acids contained in the gum resin of the anti-inflammatory remedy frankincense that target cathepsin G and 5-LO in neutrophils, and might thus represent suitable leads for intervention with age-associated diseases that have a chronic inflammatory component. Here, we investigated whether, in addition to BAs, other triterpene acids from frankincense interfere with 5-LO and cathepsin G. We provide a comprehensive analysis of 17 natural tetra- or pentacyclic triterpene acids for suppression of 5-LO product synthesis in human neutrophils. These triterpene acids were also investigated for their direct interference with 5-LO and cathepsin G in cell-free assays. Furthermore, our studies were expanded to 10 semi-synthetic BA derivatives. Our data reveal that besides BAs, several tetra- and pentacyclic triterpene acids are effective or even superior inhibitors of 5-LO product formation in human neutrophils, and in parallel, inhibit cathepsin G. Their beneficial target profile may qualify triterpene acids as anti-inflammatory natural products and pharmacological leads for intervention with diseases related to aging. Full article

(This article belongs to the Special Issue Plant Derived Natural Products and Age Related Diseases)

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13 pages, 10518 KiB

Open AccessArticle

Resveratrol-Inspired Benzo[b]selenophenes Act as Anti-Oxidants in Yeast

by Dominika Mániková^1,*, Zuzana Šestáková¹, Jana Rendeková¹, Danuša Vlasáková¹, Patrícia Lukáčová¹, Edgars Paegle², Pavel Arsenyan^2,* and Miroslav Chovanec^1,*

¹ Department of Genetics, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Dúbravská Cesta 9, 845 05 Bratislava, Slovakia

² Department of Medicinal Chemistry, Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia

Molecules 2018, 23(2), 507; https://doi.org/10.3390/molecules23020507 - 24 Feb 2018

Cited by 18 | Viewed by 5685

Abstract

Resveratrol is a natural (poly)phenol primarily found in plants protecting them against pathogens, as well as harmful effects of physical and chemical agents. In higher eukaryotic cells and organisms, this compound displays a remarkable range of biological activities, such as anti-oxidant, anti-inflammatory, anti-cancer, [...] Read more.

Resveratrol is a natural (poly)phenol primarily found in plants protecting them against pathogens, as well as harmful effects of physical and chemical agents. In higher eukaryotic cells and organisms, this compound displays a remarkable range of biological activities, such as anti-oxidant, anti-inflammatory, anti-cancer, anti-aging, cardio- and neuro-protective properties. Here, biological activities of synthetic selenium-containing derivatives of resveratrol—benzo[b]selenophenes—have been studied in lower eukaryotes Saccharomyces cerevisiae. Their toxicity, as well as DNA damaging and reactive oxygen species (ROS) inducing potencies, manifested through their ability to act as redox active anti-microbial agents, have been examined. We show that some benzo[b]selenophenes can kill yeast cells and that the killing effects are not mediated by DNA damage types that can be detected as DNA double-strand breaks. These benzo[b]selenophenes could potentially be used as anti-fungal agents, although their concentrations relevant to application in humans need to be further evaluated. In addition, most of the studied benzo[b]selenophenes display redox-modulating/anti-oxidant activity (comparable or even higher than that of resveratrol or Trolox) causing a decrease in the intracellular ROS levels in yeast cells. Therefore, after careful re-evaluation in other biological systems these observations might be transferred to humans, where resveratrol-inspired benzo[b]selenophenes could be used as supra-anti-oxidant supplements. Full article

(This article belongs to the Special Issue Small Molecule Catalysts with Therapeutic Potential)

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17 pages, 7348 KiB

Open AccessArticle

Physicochemical Characterization and Functional Analysis of the Polysaccharide from the Edible Microalga Nostoc sphaeroides

by Haifeng Li¹, Linnan Su¹, Sheng Chen², Libin Zhao², Hongyu Wang¹, Fei Ding¹, Hong Chen¹, Ruona Shi¹, Yulan Wang² and Zebo Huang^1,3,*

¹ Center for Bioresources & Drug Discovery and School of Biosciences & Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China

² Research & Development Centre, Hunan Yandi Bioengineering Co., Ltd., Zhuzhou 412000, China

³ School of Food Science and Engineering, South China University of Technology, Guangzhou 510641, China

Molecules 2018, 23(2), 508; https://doi.org/10.3390/molecules23020508 - 24 Feb 2018

Cited by 44 | Viewed by 7093

Abstract

Nostoc colonies have been used as food and medicine for centuries, and their main supporting matrix is polysaccharides, which help Nostoc cells resist various environmental stresses including oxidative stress. Here we isolated a polysaccharide, nostoglycan, from cultured Nostoc sphaeroides colonies and determined its [...] Read more.

Nostoc colonies have been used as food and medicine for centuries, and their main supporting matrix is polysaccharides, which help Nostoc cells resist various environmental stresses including oxidative stress. Here we isolated a polysaccharide, nostoglycan, from cultured Nostoc sphaeroides colonies and determined its physicochemical properties, which revealed a characteristic infrared absorption spectrum typical of polysaccharides and an amorphous morphology with rough surfaces. We also show that nostoglycan has strong moisture absorption and retention capacities and a high relative viscosity. Using Caenorhabditis elegans models, we then demonstrate that nostoglycan is capable of improving overall survival rate of the animals under increased oxidative stress caused by paraquat. Nostoglycan also reduces reactive oxygen species level, inhibits protein carbonyl formation and lipid peroxidation, and increases activities of superoxide dismutase and catalase in paraquat-exposed nematodes. As oxidative stress may drive tumor progression, we further demonstrate that nostoglycan can suppress the proliferation of several types of tumor cells and induce apoptosis of human lung adenocarcinoma A549 cells via caspase-3 activation. Together, our results yield important information on the physicochemical characteristics and demonstrate the antioxidant and anti-proliferative functions of nostoglycan, and thus provide an insight into its potential in food and health industries. Full article

(This article belongs to the Special Issue Advances in Natural Polysaccharides Research)

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Review

Jump to: Editorial, Research

19 pages, 12318 KiB

Open AccessReview

Chemical Modification of Chitosan for Efficient Vaccine Delivery

by Lei Xing^1,2,3,4,†, Ya-Tong Fan^1,†, Tian-Jiao Zhou¹, Jia-Hui Gong¹, Lian-Hua Cui⁵, Ki-Hyun Cho⁶, Yun-Jaie Choi⁶, Hu-Lin Jiang^1,2,3,4,* and Chong-Su Cho^6,*

¹ State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China

² Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical University, Nanjing 210009, China

³ Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China

⁴ Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China

⁵ Department of Animal Science, College of Agriculture Science, Yanbian University, Yanji, Jilin 133002, China

⁶ Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 229; https://doi.org/10.3390/molecules23020229 - 25 Jan 2018

Cited by 73 | Viewed by 8846

Abstract

Chitosan, which exhibits good biocompatibility, safety, microbial degradation and other excellent performances, has found application in all walks of life. In the field of medicine, usage of chitosan for the delivery of vaccine is favored by a wide range of researchers. However, due [...] Read more.

Chitosan, which exhibits good biocompatibility, safety, microbial degradation and other excellent performances, has found application in all walks of life. In the field of medicine, usage of chitosan for the delivery of vaccine is favored by a wide range of researchers. However, due to its own natural limitations, its application has been constrained to the beginning of study. In order to improve the applicability for vaccine delivery, researchers have carried out various chemical modifications of chitosan. This review summarizes a variety of modification methods and applications of chitosan and its derivatives in the field of vaccine delivery. Full article

(This article belongs to the Special Issue Chitin and Chitosan Derivatives: Biological Activities and Application)

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27 pages, 5329 KiB

Open AccessReview

NMR-Fragment Based Virtual Screening: A Brief Overview

by Meenakshi Singh, Benjamin Tam and Barak Akabayov^*

Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel

Molecules 2018, 23(2), 233; https://doi.org/10.3390/molecules23020233 - 25 Jan 2018

Cited by 37 | Viewed by 9690

Abstract

Fragment-based drug discovery (FBDD) using NMR has become a central approach over the last twenty years for development of small molecule inhibitors against biological macromolecules, to control a variety of cellular processes. Yet, several considerations should be taken into account for obtaining a [...] Read more.

Fragment-based drug discovery (FBDD) using NMR has become a central approach over the last twenty years for development of small molecule inhibitors against biological macromolecules, to control a variety of cellular processes. Yet, several considerations should be taken into account for obtaining a therapeutically relevant agent. In this review, we aim to list the considerations that make NMR fragment screening a successful process for yielding potent inhibitors. Factors that may govern the competence of NMR in fragment based drug discovery are discussed, as well as later steps that involve optimization of hits obtained by NMR-FBDD. Full article

(This article belongs to the Special Issue Recent Advances in Biomolecular NMR Spectroscopy)

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15 pages, 3293 KiB

Open AccessReview

Ultrafast Chemistry of Water Radical Cation, H₂O^•+, in Aqueous Solutions

by Jun Ma

, Furong Wang

and Mehran Mostafavi^*

Laboratoire de Chimie Physique, CNRS/Université Paris-Sud 11, Bâtiment 349, 91405 Orsay, France

Molecules 2018, 23(2), 244; https://doi.org/10.3390/molecules23020244 - 26 Jan 2018

Cited by 76 | Viewed by 8516

Abstract

Oxidation reactions by radicals constitute a very important class of chemical reactions in solution. Radiation Chemistry methods allow producing, in a controlled way, very reactive oxidizing radicals, such as OH^•, CO₃^•–, NO₃^•, SO₄^•– [...] Read more.

Oxidation reactions by radicals constitute a very important class of chemical reactions in solution. Radiation Chemistry methods allow producing, in a controlled way, very reactive oxidizing radicals, such as OH^•, CO₃^•–, NO₃^•, SO₄^•–, and N₃^•. Although the radical cation of water, H₂O^•+, with a very short lifetime (shorter than 1 ps) is the precursor of these radicals in aqueous solutions, its chemistry is usually known to be limited to the reaction of proton transfer by forming OH^• radical. Herein, we stress situations where H₂O^•+ undergoes electron transfer reaction in competition with proton transfer. Full article

(This article belongs to the Special Issue Radical Chemistry)

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11 pages, 220 KiB

Open AccessFeature PaperReview

Impact & Blast Traumatic Brain Injury: Implications for Therapy

by Satoshi Yamamoto^*,†, Douglas S. DeWitt^† and Donald S. Prough^†

¹ Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX 77555, USA

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 245; https://doi.org/10.3390/molecules23020245 - 26 Jan 2018

Cited by 29 | Viewed by 6385

Abstract

Traumatic brain injury (TBI) is one of the most frequent causes of combat casualties in Operations Iraqi Freedom (OIF), Enduring Freedom (OEF), and New Dawn (OND). Although less common than combat-related blast exposure, there have been significant numbers of blast injuries in civilian [...] Read more.

Traumatic brain injury (TBI) is one of the most frequent causes of combat casualties in Operations Iraqi Freedom (OIF), Enduring Freedom (OEF), and New Dawn (OND). Although less common than combat-related blast exposure, there have been significant numbers of blast injuries in civilian populations in the United States. Current United States Department of Defense (DoD) ICD-9 derived diagnoses of TBI in the DoD Health Care System show that, for 2016, severe and moderate TBIs accounted for just 0.7% and 12.9%, respectively, of the total of 13,634 brain injuries, while mild TBIs (mTBIs) accounted for 86% of the total. Although there is a report that there are differences in the frequency of long-term complications in mTBI between blast and non-blast TBIs, clinical presentation is classified by severity score rather than mechanism because severity scoring is associated with prognosis in clinical practice. Blast TBI (bTBI) is unique in its pathology and mechanism, but there is no treatment specific for bTBIs—these patients are treated similarly to TBIs in general and therapy is tailored on an individual basis. Currently there is no neuroprotective drug recommended by the clinical guidelines based on evidence. Full article

(This article belongs to the Special Issue Neuroprotective Agents)

34 pages, 16824 KiB

Open AccessReview

Coumarin: A Natural, Privileged and Versatile Scaffold for Bioactive Compounds

by Angela Stefanachi

, Francesco Leonetti, Leonardo Pisani

, Marco Catto^*

and Angelo Carotti

Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari “Aldo Moro”, via E. Orabona 4, I-70125 Bari, Italy

Molecules 2018, 23(2), 250; https://doi.org/10.3390/molecules23020250 - 27 Jan 2018

Cited by 442 | Viewed by 22472

Abstract

Many naturally occurring substances, traditionally used in popular medicines around the world, contain the coumarin moiety. Coumarin represents a privileged scaffold for medicinal chemists, because of its peculiar physicochemical features, and the versatile and easy synthetic transformation into a large variety of functionalized [...] Read more.

Many naturally occurring substances, traditionally used in popular medicines around the world, contain the coumarin moiety. Coumarin represents a privileged scaffold for medicinal chemists, because of its peculiar physicochemical features, and the versatile and easy synthetic transformation into a large variety of functionalized coumarins. As a consequence, a huge number of coumarin derivatives have been designed, synthesized, and tested to address many pharmacological targets in a selective way, e.g., selective enzyme inhibitors, and more recently, a number of selected targets (multitarget ligands) involved in multifactorial diseases, such as Alzheimer’s and Parkinson’s diseases. In this review an overview of the most recent synthetic pathways leading to mono- and polyfunctionalized coumarins will be presented, along with the main biological pathways of their biosynthesis and metabolic transformations. The many existing and recent reviews in the field prompted us to make some drastic selections, and therefore, the review is focused on monoamine oxidase, cholinesterase, and aromatase inhibitors, and on multitarget coumarins acting on selected targets of neurodegenerative diseases. Full article

(This article belongs to the Special Issue Versatile Coumarins)

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15 pages, 1150 KiB

Open AccessReview

Action of Phytochemicals on Insulin Signaling Pathways Accelerating Glucose Transporter (GLUT4) Protein Translocation

by Abu Sadat Md Sayem¹, Aditya Arya^2,*, Hamed Karimian², Narendiran Krishnasamy³, Ameya Ashok Hasamnis² and Chowdhury Faiz Hossain⁴

¹ Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia

² Department of Pharmacology and Therapeutics, School of Medicine, Faculty of Health and Medical Sciences, Taylor’s University, Lakeside Campus, 47500 Subang Jaya, Malaysia

³ Clinical Skills, School of Medicine, Faculty of Health and Medical Sciences, Taylor’s University, Lakeside Campus, 47500 Subang Jaya, Malaysia

⁴ Department of Pharmacy, Faculty of Sciences and Engineering, East West University, Dhaka-1212, Bangladesh

Molecules 2018, 23(2), 258; https://doi.org/10.3390/molecules23020258 - 28 Jan 2018

Cited by 64 | Viewed by 16816

Abstract

Diabetes is associated with obesity, generally accompanied by a chronic state of oxidative stress and redox imbalances which are implicated in the progression of micro- and macro-complications like heart disease, stroke, dementia, cancer, kidney failure and blindness. All these complications rise primarily due [...] Read more.

Diabetes is associated with obesity, generally accompanied by a chronic state of oxidative stress and redox imbalances which are implicated in the progression of micro- and macro-complications like heart disease, stroke, dementia, cancer, kidney failure and blindness. All these complications rise primarily due to consistent high blood glucose levels. Insulin and glucagon help to maintain the homeostasis of glucose and lipids through signaling cascades. Pancreatic hormones stimulate translocation of the glucose transporter isoform 4 (GLUT4) from an intracellular location to the cell surface and facilitate the rapid insulin-dependent storage of glucose in muscle and fat cells. Malfunction in glucose uptake mechanisms, primarily contribute to insulin resistance in type 2 diabetes. Plant secondary metabolites, commonly known as phytochemicals, are reported to have great benefits in the management of type 2 diabetes. The role of phytochemicals and their action on insulin signaling pathways through stimulation of GLUT4 translocation is crucial to understand the pathogenesis of this disease in the management process. This review will summarize the effects of phytochemicals and their action on insulin signaling pathways accelerating GLUT4 translocation based on the current literature. Full article

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20 pages, 7319 KiB

Open AccessReview

Targeting Cellular Stress Mechanisms and Metabolic Homeostasis by Chinese Herbal Drugs for Neuroprotection

by Hsiao-Chien Ting^1,†, Chia-Yu Chang^1,2,†, Kang-Yun Lu^1,3

, Hong-Meng Chuang^1,4

, Sheng-Feng Tsai⁵, Mao-Hsuan Huang^1,5, Ching-Ann Liu^1,2, Shinn-Zong Lin^1,6,* and Horng-Jyh Harn^1,7,*

¹ Bio-innovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan

² Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan

³ Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan

⁴ Agricultural Biotechnology Center, Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan

⁵ Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan

⁶ Department of Neurosurgery, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan

⁷ Department of Pathology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien 970, Taiwan

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 259; https://doi.org/10.3390/molecules23020259 - 28 Jan 2018

Cited by 9 | Viewed by 5514

Abstract

Traditional Chinese medicine has been practiced for centuries in East Asia. Herbs are used to maintain health and cure disease. Certain Chinese herbs are known to protect and improve the brain, memory, and nervous system. To apply ancient knowledge to modern science, some [...] Read more.

Traditional Chinese medicine has been practiced for centuries in East Asia. Herbs are used to maintain health and cure disease. Certain Chinese herbs are known to protect and improve the brain, memory, and nervous system. To apply ancient knowledge to modern science, some major natural therapeutic compounds in herbs were extracted and evaluated in recent decades. Emerging studies have shown that herbal compounds have neuroprotective effects or can ameliorate neurodegenerative diseases. To understand the mechanisms of herbal compounds that protect against neurodegenerative diseases, we summarize studies that discovered neuroprotection by herbal compounds and compound-related mechanisms in neurodegenerative disease models. Those compounds discussed herein show neuroprotection through different mechanisms, such as cytokine regulation, autophagy, endoplasmic reticulum (ER) stress, glucose metabolism, and synaptic function. The interleukin (IL)-1β and tumor necrosis factor (TNF)-α signaling pathways are inhibited by some compounds, thus attenuating the inflammatory response and protecting neurons from cell death. As to autophagy regulation, herbal compounds show opposite regulatory effects in different neurodegenerative models. Herbal compounds that inhibit ER stress prevent neuronal death in neurodegenerative diseases. Moreover, there are compounds that protect against neuronal death by affecting glucose metabolism and synaptic function. Since the progression of neurodegenerative diseases is complicated, and compound-related mechanisms for neuroprotection differ, therapeutic strategies may need to involve multiple compounds and consider the type and stage of neurodegenerative diseases. Full article

(This article belongs to the Special Issue Neuroprotective Agents)

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47 pages, 13174 KiB

Open AccessFeature PaperReview

Chiral Drug Analysis in Forensic Chemistry: An Overview

by Cláudia Ribeiro^1,2

, Cristiana Santos¹

, Valter Gonçalves³

, Ana Ramos⁴, Carlos Afonso^2,3

and Maria Elizabeth Tiritan^1,2,3,*

¹ Institute of Research and Advanced Training in Health Sciences and Technologies, Cooperativa de Ensino Superior Politécnico e Universitário (CESPU), Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Portugal

² Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), University of Porto, Edifício do Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n, 4050-208 Matosinhos, Portugal

³ Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto , Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal

⁴ Institute of Science and Innovation in Mechanical and Industrial Engineering (INEGI), Faculty of Engineering of the University of Porto, Rua Dr. Roberto Frias, 400, 4200-465 Porto, Portugal

Molecules 2018, 23(2), 262; https://doi.org/10.3390/molecules23020262 - 28 Jan 2018

Cited by 66 | Viewed by 11714

Abstract

Many substances of forensic interest are chiral and available either as racemates or pure enantiomers. Application of chiral analysis in biological samples can be useful for the determination of legal or illicit drugs consumption or interpretation of unexpected toxicological effects. Chiral substances can [...] Read more.

Many substances of forensic interest are chiral and available either as racemates or pure enantiomers. Application of chiral analysis in biological samples can be useful for the determination of legal or illicit drugs consumption or interpretation of unexpected toxicological effects. Chiral substances can also be found in environmental samples and revealed to be useful for determination of community drug usage (sewage epidemiology), identification of illicit drug manufacturing locations, illegal discharge of sewage and in environmental risk assessment. Thus, the purpose of this paper is to provide an overview of the application of chiral analysis in biological and environmental samples and their relevance in the forensic field. Most frequently analytical methods used to quantify the enantiomers are liquid and gas chromatography using both indirect, with enantiomerically pure derivatizing reagents, and direct methods recurring to chiral stationary phases. Full article

(This article belongs to the Special Issue Chirality in Health and Environment: Recent developments)

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13 pages, 5056 KiB

Open AccessFeature PaperReview

Metal-Incorporated Mesoporous Silicates: Tunable Catalytic Properties and Applications

by Anand Ramanathan¹

and Bala Subramaniam^1,2,*

¹ Center for Environmentally Beneficial Catalysis, The University of Kansas, Lawrence, KS 66047, USA

² Department of Chemical and Petroleum Engineering, The University of Kansas, Lawrence, KS 66045, USA

Molecules 2018, 23(2), 263; https://doi.org/10.3390/molecules23020263 - 29 Jan 2018

Cited by 18 | Viewed by 5080

Abstract

A relatively new class of three-dimensional ordered mesoporous silicates, KIT-6, incorporated with Earth-abundant metals such as Zr, Nb, and W (termed as M-KIT-6), show remarkable tunability of acidity and metal dispersion depending on the metal content, type, and synthetic method. The metal-incorporation is [...] Read more.

A relatively new class of three-dimensional ordered mesoporous silicates, KIT-6, incorporated with Earth-abundant metals such as Zr, Nb, and W (termed as M-KIT-6), show remarkable tunability of acidity and metal dispersion depending on the metal content, type, and synthetic method. The metal-incorporation is carried out using one-pot synthesis procedures that are amenable to easy scale-up. By such tuning, M-KIT-6 catalysts are shown to provide remarkable activity and selectivity in industrially-significant reactions, such as alcohol dehydration, ethylene epoxidation, and metathesis of 2-butene and ethylene. We review how the catalytic properties of M-KIT-6 materials may be tailored depending on the application to optimize performance. Full article

(This article belongs to the Special Issue Zeolites and Related Nanoporous Materials: Synthesis, Characterization and Applications in Catalysis and Green Chemistry)

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37 pages, 14180 KiB

Open AccessReview

Synthesis and Self-Assembly of Chiral Cylindrical Molecular Complexes: Functional Heterogeneous Liquid-Solid Materials Formed by Helicene Oligomers

by Nozomi Saito and Masahiko Yamaguchi^*

Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan

Molecules 2018, 23(2), 277; https://doi.org/10.3390/molecules23020277 - 29 Jan 2018

Cited by 11 | Viewed by 8624

Abstract

Chiral cylindrical molecular complexes of homo- and hetero-double-helices derived from helicene oligomers self-assemble in solution, providing functional heterogeneous liquid-solid materials. Gels and liotropic liquid crystals are formed by fibril self-assembly in solution; molecular monolayers and fibril films are formed by self-assembly on solid [...] Read more.

Chiral cylindrical molecular complexes of homo- and hetero-double-helices derived from helicene oligomers self-assemble in solution, providing functional heterogeneous liquid-solid materials. Gels and liotropic liquid crystals are formed by fibril self-assembly in solution; molecular monolayers and fibril films are formed by self-assembly on solid surfaces; gels containing gold nanoparticles emit light; silica nanoparticles aggregate and adsorb double-helices. Notable dynamics appears during self-assembly, including multistep self-assembly, solid surface catalyzed double-helix formation, sigmoidal and stairwise kinetics, molecular recognition of nanoparticles, discontinuous self-assembly, materials clocking, chiral symmetry breaking and homogeneous-heterogeneous transitions. These phenomena are derived from strong intercomplex interactions of chiral cylindrical molecular complexes. Full article

(This article belongs to the Section Nanochemistry)

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19 pages, 2475 KiB

Open AccessReview

MiR200 and miR302: Two Big Families Influencing Stem Cell Behavior

by Francesca Balzano¹

, Sara Cruciani^1,2

, Valentina Basoli^1,2

, Sara Santaniello^1,2

, Federica Facchin³

, Carlo Ventura^2,4

and Margherita Maioli^1,2,5,6,*

¹ Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy

² Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, Innovation Accelerator, CNR, Via Piero Gobetti 101, 40129 Bologna, Italy

³ Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Via Massarenti 9, 40138 Bologna, Italy

⁴ GUNA ATTRE (Advanced Therapies and Tissue REgeneration), Innovation Accelerator, CNR, Via Piero Gobetti 101, 40129 Bologna, Italy

⁵ Istituto di RicercaGenetica e Biomedica, Consiglio Nazionaledelle Ricerche (CNR), Monserrato, 09042 Cagliari, Italy

⁶ Center for Developmental Biology and Reprogramming (CEDEBIOR), Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy

Molecules 2018, 23(2), 282; https://doi.org/10.3390/molecules23020282 - 30 Jan 2018

Cited by 34 | Viewed by 6379

Abstract

In this review, we described different factors that modulate pluripotency in stem cells, in particular we aimed at following the steps of two large families of miRNAs: the miR-200 family and the miR-302 family. We analyzed some factors tuning stem cells behavior as [...] Read more.

In this review, we described different factors that modulate pluripotency in stem cells, in particular we aimed at following the steps of two large families of miRNAs: the miR-200 family and the miR-302 family. We analyzed some factors tuning stem cells behavior as TGF-β, which plays a pivotal role in pluripotency inhibition together with specific miRNAs, reactive oxygen species (ROS), but also hypoxia, and physical stimuli, such as ad hoc conveyed electromagnetic fields. TGF-β plays a crucial role in the suppression of pluripotency thus influencing the achievement of a specific phenotype. ROS concentration can modulate TGF-β activation that in turns down regulates miR-200 and miR-302. These two miRNAs are usually requested to maintain pluripotency, while they are down-regulated during the acquirement of a specific cellular phenotype. Moreover, also physical stimuli, such as extremely-low frequency electromagnetic fields or high-frequency electromagnetic fields conveyed with a radioelectric asymmetric conveyer (REAC), and hypoxia can deeply influence stem cell behavior by inducing the appearance of specific phenotypes, as well as a direct reprogramming of somatic cells. Unraveling the molecular mechanisms underlying the complex interplay between externally applied stimuli and epigenetic events could disclose novel target molecules to commit stem cell fate. Full article

(This article belongs to the Section Chemical Biology)

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31 pages, 605 KiB

Open AccessReview

Peptides as Potential Therapeutics for Alzheimer’s Disease

by Samo Ribarič

Institute of Pathophysiology, Faculty of Medicine, Zaloška 4, SI-1000 Ljubljana, Slovenia

Molecules 2018, 23(2), 283; https://doi.org/10.3390/molecules23020283 - 30 Jan 2018

Cited by 50 | Viewed by 6954

Abstract

Intracellular synthesis, folding, trafficking and degradation of proteins are controlled and integrated by proteostasis. The frequency of protein misfolding disorders in the human population, e.g., in Alzheimer’s disease (AD), is increasing due to the aging population. AD treatment options are limited to symptomatic [...] Read more.

Intracellular synthesis, folding, trafficking and degradation of proteins are controlled and integrated by proteostasis. The frequency of protein misfolding disorders in the human population, e.g., in Alzheimer’s disease (AD), is increasing due to the aging population. AD treatment options are limited to symptomatic interventions that at best slow-down disease progression. The key biochemical change in AD is the excessive accumulation of per-se non-toxic and soluble amyloid peptides (Aβ(1-37/44), in the intracellular and extracellular space, that alters proteostasis and triggers Aβ modification (e.g., by reactive oxygen species (ROS)) into toxic intermediate, misfolded soluble Aβ peptides, Aβ dimers and Aβ oligomers. The toxic intermediate Aβ products aggregate into progressively less toxic and less soluble protofibrils, fibrils and senile plaques. This review focuses on peptides that inhibit toxic Aβ oligomerization, Aβ aggregation into fibrils, or stabilize Aβ peptides in non-toxic oligomers, and discusses their potential for AD treatment. Full article

(This article belongs to the Special Issue Peptide Therapeutics)

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18 pages, 2929 KiB

Open AccessFeature PaperReview

Overcoming Aminoglycoside Enzymatic Resistance: Design of Novel Antibiotics and Inhibitors

by Sandra G. Zárate¹

, M. Luisa De la Cruz Claure², Raúl Benito-Arenas³, Julia Revuelta³, Andrés G. Santana^3,* and Agatha Bastida^3,*

¹ Facultad de Tecnología-Carrera de Ingeniería Química, Universidad Mayor Real y Pontificia de San Francisco Xavier de Chuquisaca, Regimiento Campos 180, Casilla 60-B, Sucre, Bolivia

² Facultad de Ciencias Químico Farmacéuticas y Bioquímicas, Universidad Mayor Real y Pontificia de San Francisco Xavier de Chuquisaca, Dalence 51, Casilla 497, Sucre, Bolivia

³ Departmento de Química Bio-Orgánica, Instituto de Química Orgánica General (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain

Molecules 2018, 23(2), 284; https://doi.org/10.3390/molecules23020284 - 30 Jan 2018

Cited by 64 | Viewed by 13446

Abstract

Resistance to aminoglycoside antibiotics has had a profound impact on clinical practice. Despite their powerful bactericidal activity, aminoglycosides were one of the first groups of antibiotics to meet the challenge of resistance. The most prevalent source of clinically relevant resistance against these therapeutics [...] Read more.

Resistance to aminoglycoside antibiotics has had a profound impact on clinical practice. Despite their powerful bactericidal activity, aminoglycosides were one of the first groups of antibiotics to meet the challenge of resistance. The most prevalent source of clinically relevant resistance against these therapeutics is conferred by the enzymatic modification of the antibiotic. Therefore, a deeper knowledge of the aminoglycoside-modifying enzymes and their interactions with the antibiotics and solvent is of paramount importance in order to facilitate the design of more effective and potent inhibitors and/or novel semisynthetic aminoglycosides that are not susceptible to modifying enzymes. Full article

(This article belongs to the Special Issue Recent Development on the New Applications of Aminoglycosides)

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25 pages, 2218 KiB

Open AccessReview

PTEN Inhibition in Human Disease Therapy

by Rafael Pulido^1,2

¹ Biomarkers in Cancer Unit, Biocruces Health Research Institute, 48903 Barakaldo, Spain

² IKERBASQUE, Basque Foundation for Science, 48013 Bilbao, Spain

Molecules 2018, 23(2), 285; https://doi.org/10.3390/molecules23020285 - 30 Jan 2018

Cited by 54 | Viewed by 7428

Abstract

The tumor suppressor PTEN is a major homeostatic regulator, by virtue of its lipid phosphatase activity against phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3], which downregulates the PI3K/AKT/mTOR prosurvival signaling, as well as by its protein phosphatase activity towards specific protein targets. PTEN catalytic activity is crucial [...] Read more.

The tumor suppressor PTEN is a major homeostatic regulator, by virtue of its lipid phosphatase activity against phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3], which downregulates the PI3K/AKT/mTOR prosurvival signaling, as well as by its protein phosphatase activity towards specific protein targets. PTEN catalytic activity is crucial to control cell growth under physiologic and pathologic situations, and it impacts not only in preventing tumor cell survival and proliferation, but also in restraining several cellular regeneration processes, such as those associated with nerve injury recovery, cardiac ischemia, or wound healing. In these conditions, inhibition of PTEN catalysis is being explored as a potentially beneficial therapeutic intervention. Here, an overview of human diseases and conditions in which PTEN inhibition could be beneficial is presented, together with an update on the current status of specific small molecule inhibitors of PTEN enzymatic activity, their use in experimental models, and their limitations as research or therapeutic drugs. Full article

(This article belongs to the Special Issue Protein-Tyrosine Phosphatase Inhibitors)

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17 pages, 466 KiB

Open AccessFeature PaperReview

Liposomes: Clinical Applications and Potential for Image-Guided Drug Delivery

by Narottam Lamichhane^1,*, Thirupandiyur S. Udayakumar², Warren D. D’Souza¹, Charles B. Simone II¹, Srinivasa R. Raghavan³, Jerimy Polf¹ and Javed Mahmood¹

¹ Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, USA

² Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, FL 33136, USA

³ Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, MD 20742, USA

Molecules 2018, 23(2), 288; https://doi.org/10.3390/molecules23020288 - 30 Jan 2018

Cited by 204 | Viewed by 11676

Abstract

Liposomes have been extensively studied and are used in the treatment of several diseases. Liposomes improve the therapeutic efficacy by enhancing drug absorption while avoiding or minimizing rapid degradation and side effects, prolonging the biological half-life and reducing toxicity. The unique feature of [...] Read more.

Liposomes have been extensively studied and are used in the treatment of several diseases. Liposomes improve the therapeutic efficacy by enhancing drug absorption while avoiding or minimizing rapid degradation and side effects, prolonging the biological half-life and reducing toxicity. The unique feature of liposomes is that they are biocompatible and biodegradable lipids, and are inert and non-immunogenic. Liposomes can compartmentalize and solubilize both hydrophilic and hydrophobic materials. All these properties of liposomes and their flexibility for surface modification to add targeting moieties make liposomes more attractive candidates for use as drug delivery vehicles. There are many novel liposomal formulations that are in various stages of development, to enhance therapeutic effectiveness of new and established drugs that are in preclinical and clinical trials. Recent developments in multimodality imaging to better diagnose disease and monitor treatments embarked on using liposomes as diagnostic tool. Conjugating liposomes with different labeling probes enables precise localization of these liposomal formulations using various modalities such as PET, SPECT, and MRI. In this review, we will briefly review the clinical applications of liposomal formulation and their potential imaging properties. Full article

(This article belongs to the Special Issue Liposomes as Drug Carriers)

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28 pages, 1386 KiB

Open AccessReview

Cell Penetrating Peptides as Molecular Carriers for Anti-Cancer Agents

by Antonella Borrelli^†, Anna Lucia Tornesello^†

, Maria Lina Tornesello

and Franco M. Buonaguro^*

¹ Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS Fondazione Pascale, 80131 Naples, Italy

^† These authors equally contributed to this work.

Molecules 2018, 23(2), 295; https://doi.org/10.3390/molecules23020295 - 31 Jan 2018

Cited by 208 | Viewed by 14762

Abstract

Cell membranes with their selective permeability play important functions in the tight control of molecular exchanges between the cytosol and the extracellular environment as the intracellular membranes do within the internal compartments. For this reason the plasma membranes often represent a challenging obstacle [...] Read more.

Cell membranes with their selective permeability play important functions in the tight control of molecular exchanges between the cytosol and the extracellular environment as the intracellular membranes do within the internal compartments. For this reason the plasma membranes often represent a challenging obstacle to the intracellular delivery of many anti-cancer molecules. The active transport of drugs through such barrier often requires specific carriers able to cross the lipid bilayer. Cell penetrating peptides (CPPs) are generally 5–30 amino acids long which, for their ability to cross cell membranes, are widely used to deliver proteins, plasmid DNA, RNA, oligonucleotides, liposomes and anti-cancer drugs inside the cells. In this review, we describe the several types of CPPs, the chemical modifications to improve their cellular uptake, the different mechanisms to cross cell membranes and their biological properties upon conjugation with specific molecules. Special emphasis has been given to those with promising application in cancer therapy. Full article

(This article belongs to the Special Issue Peptide Therapeutics)

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14 pages, 999 KiB

Open AccessReview

A Systematic Review of Antiamyloidogenic and Metal-Chelating Peptoids: Two Structural Motifs for the Treatment of Alzheimer’s Disease

by Sherri C. Young

Department of Chemistry, Muhlenberg College, 2400 Chew Street, Allentown, PA 18104, USA

Molecules 2018, 23(2), 296; https://doi.org/10.3390/molecules23020296 - 31 Jan 2018

Cited by 11 | Viewed by 5793

Abstract

Alzheimer’s disease (AD) is an incurable form of dementia affecting millions of people worldwide and costing billions of dollars in health care-related payments, making the discovery of a cure a top health, societal, and economic priority. Peptide-based drugs and immunotherapies targeting AD-associated beta-amyloid [...] Read more.

Alzheimer’s disease (AD) is an incurable form of dementia affecting millions of people worldwide and costing billions of dollars in health care-related payments, making the discovery of a cure a top health, societal, and economic priority. Peptide-based drugs and immunotherapies targeting AD-associated beta-amyloid (Aβ) aggregation have been extensively explored; however, their therapeutic potential is limited by unfavorable pharmacokinetic (PK) properties. Peptoids (N-substituted glycine oligomers) are a promising class of peptidomimetics with highly tunable secondary structures and enhanced stabilities and membrane permeabilities. In this review, the biological activities, structures, and physicochemical properties for several amyloid-targeting peptoids will be described. In addition, metal-chelating peptoids with the potential to treat AD will be discussed since there are connections between the dysregulation of certain metals and the amyloid pathway. Full article

(This article belongs to the Special Issue 25th Anniversary of the Amyloid Hypothesis and Alzheimer Disease)

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27 pages, 7006 KiB

Open AccessReview

Advances in the Development of PET Ligands Targeting Histone Deacetylases for the Assessment of Neurodegenerative Diseases

by Tetsuro Tago and Jun Toyohara^*

Research Team for Neuroimaging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan

Molecules 2018, 23(2), 300; https://doi.org/10.3390/molecules23020300 - 31 Jan 2018

Cited by 25 | Viewed by 5583

Abstract

Epigenetic alterations of gene expression have emerged as a key factor in several neurodegenerative diseases. In particular, inhibitors targeting histone deacetylases (HDACs), which are enzymes responsible for deacetylation of histones and other proteins, show therapeutic effects in animal neurodegenerative disease models. However, the [...] Read more.

Epigenetic alterations of gene expression have emerged as a key factor in several neurodegenerative diseases. In particular, inhibitors targeting histone deacetylases (HDACs), which are enzymes responsible for deacetylation of histones and other proteins, show therapeutic effects in animal neurodegenerative disease models. However, the details of the interaction between changes in HDAC levels in the brain and disease progression remain unknown. In this review, we focus on recent advances in development of radioligands for HDAC imaging in the brain with positron emission tomography (PET). We summarize the results of radiosynthesis and biological evaluation of the HDAC ligands to identify their successful results and challenges. Since 2006, several small molecules that are radiolabeled with a radioisotope such as carbon-11 or fluorine-18 have been developed and evaluated using various assays including in vitro HDAC binding assays and PET imaging in rodents and non-human primates. Although most compounds do not readily cross the blood-brain barrier, adamantane-conjugated radioligands tend to show good brain uptake. Until now, only one HDAC radioligand has been tested clinically in a brain PET study. Further PET imaging studies to clarify age-related and disease-related changes in HDACs in disease models and humans will increase our understanding of the roles of HDACs in neurodegenerative diseases. Full article

(This article belongs to the Special Issue Current Aspects of Radiopharmaceutical Chemistry)

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31 pages, 2072 KiB

Open AccessReview

Pineal Calcification, Melatonin Production, Aging, Associated Health Consequences and Rejuvenation of the Pineal Gland

by Dun Xian Tan^*, Bing Xu, Xinjia Zhou and Russel J. Reiter^*

Department of Cell Systems & Anatomy, UT Health San Antonio, San Antonio, TX 78229, USA

Molecules 2018, 23(2), 301; https://doi.org/10.3390/molecules23020301 - 31 Jan 2018

Cited by 134 | Viewed by 49290

Abstract

The pineal gland is a unique organ that synthesizes melatonin as the signaling molecule of natural photoperiodic environment and as a potent neuronal protective antioxidant. An intact and functional pineal gland is necessary for preserving optimal human health. Unfortunately, this gland has the [...] Read more.

The pineal gland is a unique organ that synthesizes melatonin as the signaling molecule of natural photoperiodic environment and as a potent neuronal protective antioxidant. An intact and functional pineal gland is necessary for preserving optimal human health. Unfortunately, this gland has the highest calcification rate among all organs and tissues of the human body. Pineal calcification jeopardizes melatonin’s synthetic capacity and is associated with a variety of neuronal diseases. In the current review, we summarized the potential mechanisms of how this process may occur under pathological conditions or during aging. We hypothesized that pineal calcification is an active process and resembles in some respects of bone formation. The mesenchymal stem cells and melatonin participate in this process. Finally, we suggest that preservation of pineal health can be achieved by retarding its premature calcification or even rejuvenating the calcified gland. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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51 pages, 6620 KiB

Open AccessFeature PaperReview

Marine Natural Peptides: Determination of Absolute Configuration Using Liquid Chromatography Methods and Evaluation of Bioactivities

by Ye’ Zaw Phyo^1,2,†

, João Ribeiro^3,†

, Carla Fernandes^2,3,*, Anake Kijjoa^1,2,*

and Madalena M. M. Pinto^2,3

¹ ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal

² Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), Edifício do Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n, 4050-208 Matosinhos, Portugal

³ Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia da Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal

^† These authors equally contributed to this work.

Molecules 2018, 23(2), 306; https://doi.org/10.3390/molecules23020306 - 31 Jan 2018

Cited by 26 | Viewed by 6355

Abstract

Over the last decades, many naturally occurring peptides have attracted the attention of medicinal chemists due to their promising applicability as pharmaceuticals or as models for drugs used in therapeutics. Marine peptides are chiral molecules comprising different amino acid residues. Therefore, it is [...] Read more.

Over the last decades, many naturally occurring peptides have attracted the attention of medicinal chemists due to their promising applicability as pharmaceuticals or as models for drugs used in therapeutics. Marine peptides are chiral molecules comprising different amino acid residues. Therefore, it is essential to establish the configuration of the stereogenic carbon of their amino acid constituents for a total characterization and further synthesis to obtain higher amount of the bioactive marine peptides or as a basis for structural modifications for more potent derivatives. Moreover, it is also a crucial issue taking into account the mechanisms of molecular recognition and the influence of molecular three-dimensionality in this process. In this review, a literature survey covering the report on the determination of absolute configuration of the amino acid residues of diverse marine peptides by chromatographic methodologies is presented. A brief summary of their biological activities was also included emphasizing to the most promising marine peptides. A case study describing an experience of our group was also included. Full article

(This article belongs to the Special Issue Chirality in Health and Environment: Recent developments)

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19 pages, 295 KiB

Open AccessReview

Bioactive Compounds in Functional Meat Products

by Ewelina Pogorzelska-Nowicka^1,*

, Atanas G. Atanasov^2,3

, Jarosław Horbańczuk²

and Agnieszka Wierzbicka¹

¹ Department of Technique and Food Development, Faculty of Human Nutrition and Consumer Sciences, Warsaw University of Life Sciences (WULS-SGGW), Warsaw, Nowoursynowska Street 159c, 02-776 Warsaw, Poland

² Institute of Genetics and Animal Breeding, Polish Academy of Sciences, 05-552 Jastrzębiec, Poland

³ Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria

Molecules 2018, 23(2), 307; https://doi.org/10.3390/molecules23020307 - 31 Jan 2018

Cited by 100 | Viewed by 9365

Abstract

Meat and meat products are a good source of bioactive compounds with positive effect on human health such as vitamins, minerals, peptides or fatty acids. Growing food consumer awareness and intensified global meat producers competition puts pressure on creating new healthier meat products. [...] Read more.

Meat and meat products are a good source of bioactive compounds with positive effect on human health such as vitamins, minerals, peptides or fatty acids. Growing food consumer awareness and intensified global meat producers competition puts pressure on creating new healthier meat products. In order to meet these expectations, producers use supplements with functional properties for animal diet and as direct additives for meat products. In the presented work seven groups of key functional constituents were chosen: (i) fatty acids; (ii) minerals; (iii) vitamins; (iv) plant antioxidants; (v) dietary fibers; (vi) probiotics and (vii) bioactive peptides. Each of them is discussed in term of their impact on human health as well as some quality attributes of the final products. Full article

21 pages, 665 KiB

Open AccessReview

Physico-Chemical Conversion of Lignocellulose: Inhibitor Effects and Detoxification Strategies: A Mini Review

by Daehwan Kim

Laboratory of Renewable Resources Engineering, Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA

Molecules 2018, 23(2), 309; https://doi.org/10.3390/molecules23020309 - 1 Feb 2018

Cited by 349 | Viewed by 11649

Abstract

A pretreatment of lignocellulosic biomass to produce biofuels, polymers, and other chemicals plays a vital role in the biochemical conversion process toward disrupting the closely associated structures of the cellulose-hemicellulose-lignin molecules. Various pretreatment steps alter the chemical/physical structure of lignocellulosic materials by solubilizing [...] Read more.

A pretreatment of lignocellulosic biomass to produce biofuels, polymers, and other chemicals plays a vital role in the biochemical conversion process toward disrupting the closely associated structures of the cellulose-hemicellulose-lignin molecules. Various pretreatment steps alter the chemical/physical structure of lignocellulosic materials by solubilizing hemicellulose and/or lignin, decreasing the particle sizes of substrate and the crystalline portions of cellulose, and increasing the surface area of biomass. These modifications enhance the hydrolysis of cellulose by increasing accessibilities of acids or enzymes onto the surface of cellulose. However, lignocellulose-derived byproducts, which can inhibit and/or deactivate enzyme and microbial biocatalysts, are formed, including furan derivatives, lignin-derived phenolics, and carboxylic acids. These generation of compounds during pretreatment with inhibitory effects can lead to negative effects on subsequent steps in sugar flat-form processes. A number of physico-chemical pretreatment methods such as steam explosion, ammonia fiber explosion (AFEX), and liquid hot water (LHW) have been suggested and developed for minimizing formation of inhibitory compounds and alleviating their effects on ethanol production processes. This work reviews the physico-chemical pretreatment methods used for various biomass sources, formation of lignocellulose-derived inhibitors, and their contributions to enzymatic hydrolysis and microbial activities. Furthermore, we provide an overview of the current strategies to alleviate inhibitory compounds present in the hydrolysates or slurries. Full article

(This article belongs to the Section Green Chemistry)

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26 pages, 4213 KiB

Open AccessReview

The Road from Host-Defense Peptides to a New Generation of Antimicrobial Drugs

by Alicia Boto^*, Jose Manuel Pérez de la Lastra

and Concepción C. González

Instituto de Productos Naturales y Agrobiología del CSIC, CSIC-Spanish Research Council, Avda. Astrofísico Fco. Sánchez, 3-38206 La Laguna, Tenerife, Spain

Molecules 2018, 23(2), 311; https://doi.org/10.3390/molecules23020311 - 1 Feb 2018

Cited by 102 | Viewed by 10020

Abstract

Host-defense peptides, also called antimicrobial peptides (AMPs), whose protective action has been used by animals for millions of years, fulfill many requirements of the pharmaceutical industry, such as: (1) broad spectrum of activity; (2) unlike classic antibiotics, they induce very little resistance; (3) [...] Read more.

Host-defense peptides, also called antimicrobial peptides (AMPs), whose protective action has been used by animals for millions of years, fulfill many requirements of the pharmaceutical industry, such as: (1) broad spectrum of activity; (2) unlike classic antibiotics, they induce very little resistance; (3) they act synergically with conventional antibiotics; (4) they neutralize endotoxins and are active in animal models. However, it is considered that many natural peptides are not suitable for drug development due to stability and biodisponibility problems, or high production costs. This review describes the efforts to overcome these problems and develop new antimicrobial drugs from these peptides or inspired by them. The discovery process of natural AMPs is discussed, as well as the development of synthetic analogs with improved pharmacological properties. The production of these compounds at acceptable costs, using different chemical and biotechnological methods, is also commented. Once these challenges are overcome, a new generation of versatile, potent and long-lasting antimicrobial drugs is expected. Full article

(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)

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33 pages, 672 KiB

Open AccessReview

Molecularly Imprinted Polymers as Extracting Media for the Chromatographic Determination of Antibiotics in Milk

by Dimitrios Bitas

and Victoria Samanidou^*

Laboratory of Analytical Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece

Molecules 2018, 23(2), 316; https://doi.org/10.3390/molecules23020316 - 2 Feb 2018

Cited by 57 | Viewed by 11468

Abstract

Milk-producing animals are typically kept stationary in overcrowded large-scale farms and in most cases under unsanitary conditions, which promotes the development of infections. In order to maintain sufficient health status among the herd or promote growth and increase production, farmers administer preventative antibiotic [...] Read more.

Milk-producing animals are typically kept stationary in overcrowded large-scale farms and in most cases under unsanitary conditions, which promotes the development of infections. In order to maintain sufficient health status among the herd or promote growth and increase production, farmers administer preventative antibiotic doses to the animals through their feed. However, many antibiotics used in cattle farms are intended for the treatment of bacterial infections in humans. This results in the development of antibiotic-resistant bacteria which pose a great risk for public health. Additionally, antibiotic residues are found in milk and dairy products, with potential toxic effects for the consumers. Hence the need of antibiotic residues monitoring in milk arises. Analytical methods were developed for the determination of antibiotics in milk, with key priority given to the analyte extraction and preconcentration step. Extraction can benefit from the production of molecularly imprinted polymers (MIPs) that can be applied as sorbents for the extraction of specific antibiotics. This review focuses on the principals of molecular imprinting technology and synthesis methods of MIPs, as well as the application of MIPs and MIPs composites for the chromatographic determination of various antibiotic categories in milk found in the recent literature. Full article

(This article belongs to the Special Issue Synthesis and Applications of Molecularly Imprinted Polymers)

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18 pages, 2430 KiB

Open AccessReview

Recent Advances in Detecting Mitochondrial DNA Heteroplasmic Variations

by Mengqin Duan, Jing Tu^*

and Zuhong Lu^*

State Key Lab of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China

Molecules 2018, 23(2), 323; https://doi.org/10.3390/molecules23020323 - 3 Feb 2018

Cited by 48 | Viewed by 9873

Abstract

The co-existence of wild-type and mutated mitochondrial DNA (mtDNA) molecules termed heteroplasmy becomes a research hot point of mitochondria. In this review, we listed several methods of mtDNA heteroplasmy research, including the enrichment of mtDNA and the way of calling heteroplasmic variations. At [...] Read more.

The co-existence of wild-type and mutated mitochondrial DNA (mtDNA) molecules termed heteroplasmy becomes a research hot point of mitochondria. In this review, we listed several methods of mtDNA heteroplasmy research, including the enrichment of mtDNA and the way of calling heteroplasmic variations. At the present, while calling the novel ultra-low level heteroplasmy, high-throughput sequencing method is dominant while the detection limit of recorded mutations is accurate to 0.01% using the other quantitative approaches. In the future, the studies of mtDNA heteroplasmy may pay more attention to the single-cell level and focus on the linkage of mutations. Full article

(This article belongs to the Special Issue Protein-DNA Interactions: From Biophysics to Genomics)

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20 pages, 1263 KiB

Open AccessReview

Cell Migration Related to MDR—Another Impediment to Effective Chemotherapy?

by Jakub Kryczka

and Joanna Boncela^*

Institute of Medical Biology, Polish Academy of Sciences, 106 Lodowa Str, 93-232 Lodz, Poland

Molecules 2018, 23(2), 331; https://doi.org/10.3390/molecules23020331 - 5 Feb 2018

Cited by 14 | Viewed by 4343

Abstract

Multidrug resistance, mediated by members of the ATP-binding cassette (ABC) proteins superfamily, has become one of the biggest obstacles in conquering tumour progression. If the chemotherapy outcome is considered successful, when the primary tumour volume is decreased or completely abolished, modulation of ABC [...] Read more.

Multidrug resistance, mediated by members of the ATP-binding cassette (ABC) proteins superfamily, has become one of the biggest obstacles in conquering tumour progression. If the chemotherapy outcome is considered successful, when the primary tumour volume is decreased or completely abolished, modulation of ABC proteins activity is one of the best methods to overcome drug resistance. However, if a positive outcome is represented by no metastasis or, at least, elongation of remission-free time, then the positive effect of ABC proteins inhibition should be compared with the several side effects it causes, which may inflict cancer progression and decrease overall patient health. Clinical trials conducted thus far have shown that the tested ABC modulators add limited or no benefits to cancer patients, as some of them are merely toxic and others induce unwanted drug–drug interactions. Moreover, the inhibition of certain ABC members has been recently indicated as potentially responsible for increased fibroblasts migration. A better understanding of the complex role of ABC proteins in relation to cancer progression may offer novel strategies in cancer therapy. Full article

(This article belongs to the Special Issue Counteracting Drug Resistant Mechanisms in Cancer)

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19 pages, 1243 KiB

Open AccessReview

Review of Current Cell-Penetrating Antibody Developments for HIV-1 Therapy

by Muhamad Alif Che Nordin¹ and Sin-Yeang Teow^2,*

¹ Kulliyyah of Medicine and Health Sciences (KMHS), Kolej Universiti INSANIAH, 09300 Kuala Ketil, Kedah, Malaysia

² Sunway Institute for Healthcare Development (SIHD), School of Healthcare and Medical Sciences (SHMS), Sunway University, Jalan Universiti, Bandar Sunway, 47500 Subang Jaya, Selangor Darul Ehsan, Malaysia

Molecules 2018, 23(2), 335; https://doi.org/10.3390/molecules23020335 - 6 Feb 2018

Cited by 8 | Viewed by 6070

Abstract

The discovery of highly active antiretroviral therapy (HAART) in 1996 has significantly reduced the global mortality and morbidity caused by the acquired immunodeficiency syndrome (AIDS). However, the therapeutic strategy of HAART that targets multiple viral proteins may render off-target toxicity and more importantly [...] Read more.

The discovery of highly active antiretroviral therapy (HAART) in 1996 has significantly reduced the global mortality and morbidity caused by the acquired immunodeficiency syndrome (AIDS). However, the therapeutic strategy of HAART that targets multiple viral proteins may render off-target toxicity and more importantly results in drug-resistant escape mutants. These have been the main challenges for HAART and refinement of this therapeutic strategy is urgently needed. Antibody-mediated treatments are emerging therapeutic modalities for various diseases. Most therapeutic antibodies have been approved by Food and Drug Administration (FDA) mainly for targeting cancers. Previous studies have also demonstrated the promising effect of therapeutic antibodies against HIV-1, but there are several limitations in this therapy, particularly when the viral targets are intracellular proteins. The conventional antibodies do not cross the cell membrane, hence, the pathogenic intracellular proteins cannot be targeted with this classical therapeutic approach. Over the years, the advancement of antibody engineering has permitted the therapeutic antibodies to comprehensively target both extra- and intra-cellular proteins in various infections and diseases. This review aims to update on the current progress in the development of antibody-based treatment against intracellular targets in HIV-1 infection. We also attempt to highlight the challenges and limitations in the development of antibody-based therapeutic modalities against HIV-1. Full article

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21 pages, 2217 KiB

Open AccessReview

Melatonin: A Molecule for Reducing Breast Cancer Risk

by Alicia González-González

, María Dolores Mediavilla and Emilio J. Sánchez-Barceló^*

Department of Physiology and Pharmacology, School of Medicina, University of Cantabria, 39011 Santander, Spain

Molecules 2018, 23(2), 336; https://doi.org/10.3390/molecules23020336 - 6 Feb 2018

Cited by 48 | Viewed by 11809

Abstract

The objective of this article is to review the basis supporting the usefulness of melatonin as an adjuvant therapy for breast cancer (BC) prevention in several groups of individuals at high risk for this disease. Melatonin, as a result of its antiestrogenic and [...] Read more.

The objective of this article is to review the basis supporting the usefulness of melatonin as an adjuvant therapy for breast cancer (BC) prevention in several groups of individuals at high risk for this disease. Melatonin, as a result of its antiestrogenic and antioxidant properties, as well as its ability to improve the efficacy and reduce the side effects of conventional antiestrogens, could safely be associated with the antiestrogenic drugs presently in use. In individuals at risk of BC due to night shift work, the light-induced inhibition of melatonin secretion, with the consequent loss of its antiestrogenic effects, would be countered by administering this neurohormone. BC risk from exposure to metalloestrogens, such as cadmium, could be treated with melatonin supplements to individuals at risk of BC due to exposure to this xenoestrogen. The BC risk related to obesity may be reduced by melatonin which decrease body fat mass, inhibits the enhanced aromatase expression in obese women, increases adiponectin secretion, counteracts the oncogenic effects of elevated concentrations of leptin; and decreases blood glucose levels and insulin resistance. Despite compelling experimental evidence of melatonin’s oncostatic actions being susceptible to lowering BC risk, there is still a paucity of clinical trials focused on this subject. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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21 pages, 1079 KiB

Open AccessReview

Interplay between P-Glycoprotein Expression and Resistance to Endoplasmic Reticulum Stressors

by Milan Hano¹, Lenka Tomášová², Mário Šereš¹, Lucia Pavlíková¹, Albert Breier^3,*

and Zdena Sulová^1,*

¹ Institute of Molecular Physiology and Genetics, Centre of Bioscience, Slovak Academy of Sciences, Dúbravska cesta 9, 84505 Bratislava, Slovakia

² Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Dúbravska cesta 9, 84505 Bratislava, Slovakia

³ Institute of Biochemistry and Microbiology, Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinského 9, 81237 Bratislava, Slovakia

Molecules 2018, 23(2), 337; https://doi.org/10.3390/molecules23020337 - 6 Feb 2018

Cited by 37 | Viewed by 6446

Abstract

Multidrug resistance (MDR) is a phenotype of cancer cells with reduced sensitivity to a wide range of unrelated drugs. P-glycoprotein (P-gp)—a drug efflux pump (ABCB1 member of the ABC transporter gene family)—is frequently observed to be a molecular cause of MDR. The drug-efflux [...] Read more.

Multidrug resistance (MDR) is a phenotype of cancer cells with reduced sensitivity to a wide range of unrelated drugs. P-glycoprotein (P-gp)—a drug efflux pump (ABCB1 member of the ABC transporter gene family)—is frequently observed to be a molecular cause of MDR. The drug-efflux activity of P-gp is considered as the underlying mechanism of drug resistance against P-gp substrates and results in failure of cancer chemotherapy. Several pathological impulses such as shortages of oxygen and glucose supply, alterations of calcium storage mechanisms and/or processes of protein N-glycosylation in the endoplasmic reticulum (ER) leads to ER stress (ERS), characterized by elevation of unfolded protein cell content and activation of the unfolded protein response (UPR). UPR is responsible for modification of protein folding pathways, removal of misfolded proteins by ER associated protein degradation (ERAD) and inhibition of proteosynthesis. However, sustained ERS may result in UPR-mediated cell death. Neoplastic cells could escape from the death pathway induced by ERS by switching UPR into pro survival mechanisms instead of apoptosis. Here, we aimed to present state of the art information about consequences of P-gp expression on mechanisms associated with ERS development and regulation of the ERAD system, particularly focused on advances in ERS-associated therapy of drug resistant malignancies. Full article

(This article belongs to the Special Issue Counteracting Drug Resistant Mechanisms in Cancer)

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21 pages, 6343 KiB

Open AccessReview

Chemical Constituents and Pharmacological Activity of Agarwood and Aquilaria Plants

by Shuai Wang^1,2,†

, Zhangxin Yu^3,4,†, Canhong Wang^3,4, Chongming Wu⁵, Peng Guo^5,* and Jianhe Wei^1,2,3,4,*

¹ Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China

² Ministry of Education & National Engineering Laboratory for Breeding of Endangered Medicinal Materials, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China

³ Conservation and Development of Southern Medicine, Hainan Branch of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Haikou 570311, China

⁴ Key Laboratory of State Administration of Traditional Chinese Medicine for Agarwood Sustainable Utilization, Hainan Branch of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Haikou 570311, China

⁵ Pharmacology and Toxicology Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 342; https://doi.org/10.3390/molecules23020342 - 7 Feb 2018

Cited by 108 | Viewed by 11648

Abstract

Agarwood, a highly precious non-timber fragrant wood of Aquilaria spp. (Thymelaeaceae), has been widely used in traditional medicine, religious rites, and cultural activities. Due to the inflated demanding and depleted natural resources, the yields of agarwood collected from the wild are shrinking, and [...] Read more.

Agarwood, a highly precious non-timber fragrant wood of Aquilaria spp. (Thymelaeaceae), has been widely used in traditional medicine, religious rites, and cultural activities. Due to the inflated demanding and depleted natural resources, the yields of agarwood collected from the wild are shrinking, and the price is constantly rising, which restricts agarwood scientific research and wide application. With the sustainable planting and management of agarwood applied, and especially the artificial-inducing methods being used in China and Southeast Asian countries, agarwood yields are increasing, and the price is becoming more reasonable. Under this condition, illuminating the scientific nature of traditional agarwood application and developing new products and drugs from agarwood have become vitally important. Recently, the phytochemical investigations have achieved fruitful results, and more than 300 compounds have been isolated, including numerous new compounds that might be the characteristic constituents with physiological action. However, no one has focused on the new compounds and presented a summary until now. Alongside phytochemical advances, bioactivity screening and pharmacological investigation have also made a certain progress. Therefore, this review discussed the new compounds isolated after 2010, and summarized the pharmacological progress on agarwood and Aquilaria plants. Full article

(This article belongs to the Special Issue Biological Activity of Secondary Metabolites)

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25 pages, 504 KiB

Open AccessReview

Practical Application of Aptamer-Based Biosensors in Detection of Low Molecular Weight Pollutants in Water Sources

by Wei Zhang

, Qing Xiu Liu, Zhi Hou Guo and Jun Sheng Lin^*

School of Medicine, Huaqiao University, Quanzhou 362021, Fujian, China

Molecules 2018, 23(2), 344; https://doi.org/10.3390/molecules23020344 - 7 Feb 2018

Cited by 68 | Viewed by 8539

Abstract

Water pollution has become one of the leading causes of human health problems. Low molecular weight pollutants, even at trace concentrations in water sources, have aroused global attention due to their toxicity after long-time exposure. There is an increased demand for appropriate methods [...] Read more.

Water pollution has become one of the leading causes of human health problems. Low molecular weight pollutants, even at trace concentrations in water sources, have aroused global attention due to their toxicity after long-time exposure. There is an increased demand for appropriate methods to detect these pollutants in aquatic systems. Aptamers, single-stranded DNA or RNA, have high affinity and specificity to each of their target molecule, similar to antigen-antibody interaction. Aptamers can be selected using a method called Systematic Evolution of Ligands by EXponential enrichment (SELEX). Recent years we have witnessed great progress in developing aptamer selection and aptamer-based sensors for low molecular weight pollutants in water sources, such as tap water, seawater, lake water, river water, as well as wastewater and its effluents. This review provides an overview of aptamer-based methods as a novel approach for detecting low molecular weight pollutants in water sources. Full article

(This article belongs to the Special Issue Nucleic Acid Aptamers)

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20 pages, 629 KiB

Open AccessFeature PaperReview

Biodegradable and Biocompatible Polyhydroxy-alkanoates (PHA): Auspicious Microbial Macromolecules for Pharmaceutical and Therapeutic Applications

by Martin Koller^1,2

¹ Office of Research Management and Service, c/o Institute of Chemistry, University of Graz, NAWI Graz, Heinrichstrasse 28/III, 8010 Graz, Austria

² Association for Resource Efficient and Sustainable Technologies—ARENA, Inffeldgasse 21b, 8010 Graz, Austria

Molecules 2018, 23(2), 362; https://doi.org/10.3390/molecules23020362 - 8 Feb 2018

Cited by 229 | Viewed by 13298

Abstract

Polyhydroxyalkanoates (PHA) are bio-based microbial biopolyesters; their stiffness, elasticity, crystallinity and degradability are tunable by the monomeric composition, selection of microbial production strain, substrates, process parameters during production, and post-synthetic processing; they display biological alternatives for diverse technomers of petrochemical origin. This, together [...] Read more.

Polyhydroxyalkanoates (PHA) are bio-based microbial biopolyesters; their stiffness, elasticity, crystallinity and degradability are tunable by the monomeric composition, selection of microbial production strain, substrates, process parameters during production, and post-synthetic processing; they display biological alternatives for diverse technomers of petrochemical origin. This, together with the fact that their monomeric and oligomeric in vivo degradation products do not exert any toxic or elsewhere negative effect to living cells or tissue of humans or animals, makes them highly stimulating for various applications in the medical field. This article provides an overview of PHA application in the therapeutic, surgical and tissue engineering area, and reviews strategies to produce PHA at purity levels high enough to be used in vivo. Tested applications of differently composed PHA and advanced follow-up products as carrier materials for controlled in vivo release of anti-cancer drugs or antibiotics, as scaffolds for tissue engineering, as guidance conduits for nerve repair or as enhanced sutures, implants or meshes are discussed from both a biotechnological and a material-scientific perspective. The article also describes the use of traditional processing techniques for production of PHA-based medical devices, such as melt-spinning, melt extrusion, or solvent evaporation, and emerging processing techniques like 3D-printing, computer-aided wet-spinning, laser perforation, and electrospinning. Full article

(This article belongs to the Special Issue Advances in Biodegradable Polymers)

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20 pages, 4316 KiB

Open AccessFeature PaperReview

Cancer Targeting and Drug Delivery Using Carbon-Based Quantum Dots and Nanotubes

by Joel Pardo¹, Zhili Peng^1,2,*

and Roger M. Leblanc^1,*

¹ Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, FL 33146, USA

² College of Pharmacy and Chemistry, Dali University, Dali 671000, Yunnan, China

Molecules 2018, 23(2), 378; https://doi.org/10.3390/molecules23020378 - 10 Feb 2018

Cited by 192 | Viewed by 13013

Abstract

Currently cancer treatment is in large part non-specific with respect to treatment. Medication is often harsh on patients, whereby they suffer several undesired side effects as a result. Carbon-based nanoparticles have attracted attention in recent years due to their ability to act as [...] Read more.

Currently cancer treatment is in large part non-specific with respect to treatment. Medication is often harsh on patients, whereby they suffer several undesired side effects as a result. Carbon-based nanoparticles have attracted attention in recent years due to their ability to act as a platform for the attachment of several drugs and/or ligands. Relatively simple models are often used in cancer research, wherein carbon nanoparticles are conjugated to a ligand that is specific to an overexpressed receptor for imaging and drug delivery in cancer treatment. These carbon nanoparticles confer unique properties to the imaging or delivery vehicle due to their nontoxic nature and their high fluorescence qualities. Chief among the ongoing research within carbon-based nanoparticles emerge carbon dots (C-dots) and carbon nanotubes (CNTs). In this review, the aforementioned carbon nanoparticles will be discussed in their use within doxorubicin and gemcitabine based drug delivery vehicles, as well as the ligand-mediated receptor specific targeted therapy. Further directions of research in current field are also discussed. Full article

(This article belongs to the Special Issue Targeted Drug Delivery and Nanocarriers)

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11 pages, 548 KiB

Open AccessReview

Anti-Cancer Activities of Diterpenoids Derived from Euphorbia fischeriana Steud

by Baiyu Jian¹, Hao Zhang², Cuicui Han³ and Jicheng Liu^2,*

¹ Graduate School of Heilongjiang University of Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin 150040, China

² Research Institute of Medicine and Pharmacy, Qiqihar Medical University, Qiqihar 161006, China

³ College of Pharmacy, Qiqihar Medical University, Qiqihar 161006, China

Molecules 2018, 23(2), 387; https://doi.org/10.3390/molecules23020387 - 11 Feb 2018

Cited by 53 | Viewed by 5837

Abstract

Euphorbia fischeriana Steud is an essential oriental folk medicine used for healing cancer, edema and tuberculosis. Recently, its anticancer activitity has attracted more attention. A volume of research has indicated that diterpenoids are the major anticancer active constituents from this medicinal herb. In [...] Read more.

Euphorbia fischeriana Steud is an essential oriental folk medicine used for healing cancer, edema and tuberculosis. Recently, its anticancer activitity has attracted more attention. A volume of research has indicated that diterpenoids are the major anticancer active constituents from this medicinal herb. In this review, we aimed to provide a summary of the promising anticancer diterpenoids from this plant; many diterpenoids mentioned in this article are newly discovered diterpenoids. According to the carbon skeleton and substituents, they can be classified into eight subtypes: ent-abietane, daphnane, tigliane, ingenane, ent-atisane, ent-rosane, ent-kaurane, and lathyrane. Futhermore, their key anticancer mechanisms and protein targets of these compounds will be discussed. These natural diterpenoids could provide a reservoir for drug discovery. Full article

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22 pages, 2660 KiB

Open AccessReview

Proteinaceous Regulators and Inhibitors of Protein Tyrosine Phosphatases

by Wiljan Hendriks^1,*

, Annika Bourgonje¹, William Leenders² and Rafael Pulido^3,4

¹ Department of Cell Biology, Radboud University Medical Center, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands

² Department of Biochemistry, Radboud University Medical Center, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands

³ Biomarkers in Cancer Unit, Biocruces Health Research Institute, 48903 Barakaldo, Spain

⁴ IKERBASQUE, Basque Foundation for Science, Bilbao, Spain

Molecules 2018, 23(2), 395; https://doi.org/10.3390/molecules23020395 - 12 Feb 2018

Cited by 21 | Viewed by 5515

Abstract

Proper control of the phosphotyrosine content in signal transduction proteins is essential for normal cell behavior and is lost in many pathologies. Attempts to normalize aberrant tyrosine phosphorylation levels in disease states currently involve either the application of small compounds that inhibit tyrosine [...] Read more.

Proper control of the phosphotyrosine content in signal transduction proteins is essential for normal cell behavior and is lost in many pathologies. Attempts to normalize aberrant tyrosine phosphorylation levels in disease states currently involve either the application of small compounds that inhibit tyrosine kinases (TKs) or the addition of growth factors or their mimetics to boost receptor-type TK activity. Therapies that target the TK enzymatic counterparts, the multi-enzyme family of protein tyrosine phosphatases (PTPs), are still lacking despite their undisputed involvement in human diseases. Efforts to pharmacologically modulate PTP activity have been frustrated by the conserved structure of the PTP catalytic core, providing a daunting problem with respect to target specificity. Over the years, however, many different protein interaction-based regulatory mechanisms that control PTP activity have been uncovered, providing alternative possibilities to control PTPs individually. Here, we review these regulatory principles, discuss existing biologics and proteinaceous compounds that affect PTP activity, and mention future opportunities to drug PTPs via these regulatory concepts. Full article

(This article belongs to the Special Issue Protein-Tyrosine Phosphatase Inhibitors)

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20 pages, 639 KiB

Open AccessReview

Mining and Development of Novel SSR Markers Using Next Generation Sequencing (NGS) Data in Plants

by Sima Taheri^1,*, Thohirah Lee Abdullah^1,*, Mohd Rafii Yusop^1,2

, Mohamed Musa Hanafi^2,3,4

, Mahbod Sahebi², Parisa Azizi² and Redmond Ramin Shamshiri⁵

¹ Department of Crop Science, Faculty of Agriculture, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

² Laboratory of Climate-Smart Food Crop Production, Institute of Tropical Agriculture and Food Security, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

³ Laboratory of Plantation Science and Technology, Institute of Plantation Studies, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

⁴ Department of Land Management, Faculty of Agriculture, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

⁵ Smart Farming Technology Research Center, Department of Biological and Agricultural Engineering, Faculty of Engineering, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia

Molecules 2018, 23(2), 399; https://doi.org/10.3390/molecules23020399 - 13 Feb 2018

Cited by 133 | Viewed by 14227

Abstract

Microsatellites, or simple sequence repeats (SSRs), are one of the most informative and multi-purpose genetic markers exploited in plant functional genomics. However, the discovery of SSRs and development using traditional methods are laborious, time-consuming, and costly. Recently, the availability of high-throughput sequencing technologies [...] Read more.

Microsatellites, or simple sequence repeats (SSRs), are one of the most informative and multi-purpose genetic markers exploited in plant functional genomics. However, the discovery of SSRs and development using traditional methods are laborious, time-consuming, and costly. Recently, the availability of high-throughput sequencing technologies has enabled researchers to identify a substantial number of microsatellites at less cost and effort than traditional approaches. Illumina is a noteworthy transcriptome sequencing technology that is currently used in SSR marker development. Although 454 pyrosequencing datasets can be used for SSR development, this type of sequencing is no longer supported. This review aims to present an overview of the next generation sequencing, with a focus on the efficient use of de novo transcriptome sequencing (RNA-Seq) and related tools for mining and development of microsatellites in plants. Full article

(This article belongs to the Section Molecular Diversity)

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23 pages, 5315 KiB

Open AccessReview

Small Molecules: Therapeutic Application in Neuropsychiatric and Neurodegenerative Disorders

by Stefania Schiavone^* and Luigia Trabace

Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli, 20, 71122 Foggia, Italy

Molecules 2018, 23(2), 411; https://doi.org/10.3390/molecules23020411 - 13 Feb 2018

Cited by 18 | Viewed by 4540

Abstract

In recent years, an increasing number of studies have been published, focusing on the potential therapeutic use of small catalytic agents with strong biological properties. So far, most of these works have only regarded specific clinical fields, such as oncology, infectivology and general [...] Read more.

In recent years, an increasing number of studies have been published, focusing on the potential therapeutic use of small catalytic agents with strong biological properties. So far, most of these works have only regarded specific clinical fields, such as oncology, infectivology and general pathology, in particular with respect to the treatment of significant inflammatory processes. However, interesting data on possible therapeutic applications of small molecules for the treatment of neuropsychiatric and neurodegenerative illnesses are emerging, especially with respect to the possibility to modulate the cellular redox state. Indeed, a crucial role of redox dysregulation in the pathogenesis of these disorders has been widely demonstrated by both pre-clinical and clinical studies, being the reduction of the total amount of free radicals a promising novel therapeutic approach for these diseases. In this review, we focused our interest on studies published during the last ten years reporting therapeutic potential of small molecules for the treatment of neuropsychiatric and neurodegenerative disorders, also based on the biological efficiency of these compounds in detecting intracellular disturbances induced by increased production of reactive oxygen species. Full article

(This article belongs to the Section Bioorganic Chemistry)

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9 pages, 718 KiB

Open AccessReview

Antibacterial Peptides in Dermatology–Strategies for Evaluation of Allergic Potential

by Milena Deptuła^1,†

, Anna Wardowska^2,†, Maria Dzierżyńska³

, Sylwia Rodziewicz-Motowidło³

and Michał Pikuła^2,*

¹ Department of Embryology, Medical University of Gdańsk, 80-211 Gdansk, Poland

² Department of Clinical Immunology and Transplantology, Medical University of Gdańsk, 80-211 Gdansk, Poland

³ Department of Biomedical Chemistry, Faculty of Chemistry, University of Gdańsk, 80-308 Gdansk, Poland

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 414; https://doi.org/10.3390/molecules23020414 - 14 Feb 2018

Cited by 26 | Viewed by 7520

Abstract

During recent decades, the market for peptide-based drugs, including antimicrobial peptides, has vastly extended and evolved. These drugs can be useful in treatment of various types of disorders, e.g., cancer, autoimmune diseases, infections, and non-healing wounds. Although peptides are less immunogenic than other [...] Read more.

During recent decades, the market for peptide-based drugs, including antimicrobial peptides, has vastly extended and evolved. These drugs can be useful in treatment of various types of disorders, e.g., cancer, autoimmune diseases, infections, and non-healing wounds. Although peptides are less immunogenic than other biologic therapeutics, they can still induce immune responses and cause allergies. It is important to evaluate the immunogenic and allergic potential of peptides before they are forwarded to the expensive stages of clinical trials. The process of the evaluation of immunogenicity and cytotoxicity is complicated, as in vitro models and bioinformatics tools cannot fully simulate situations in the clinic. Nevertheless, several potentially promising tests for the preclinical evaluation of peptide drugs have been implemented (e.g., cytotoxicity assays, the basophil activation test, and lymphocyte activation assays). In this review, we focus on strategies for evaluation of the allergic potential of peptide-based therapeutics. Full article

(This article belongs to the Special Issue Antimicrobial Peptides and Peptidomimetics)

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20 pages, 7842 KiB

Open AccessReview

AIEgen-Based Fluorescent Nanomaterials: Fabrication and Biological Applications

by Hui Gao¹, Xin Zhao²

and Sijie Chen^1,*

¹ Ming Wai Lau Centre for Reparative Medicine, Karolinska Institutet, Hong Kong, China

² Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong, China

Molecules 2018, 23(2), 419; https://doi.org/10.3390/molecules23020419 - 14 Feb 2018

Cited by 39 | Viewed by 8647

Abstract

In recent years, luminogens with the feature of aggregation-induced emission (AIEgen) have emerged as advanced luminescent materials for fluorescent nanomaterial preparation. AIEgen-based nanomaterials show enhanced fluorescence efficiency and superior photostability, which thusly offer unique advantages in biological applications. In this review, we will [...] Read more.

In recent years, luminogens with the feature of aggregation-induced emission (AIEgen) have emerged as advanced luminescent materials for fluorescent nanomaterial preparation. AIEgen-based nanomaterials show enhanced fluorescence efficiency and superior photostability, which thusly offer unique advantages in biological applications. In this review, we will summarize the fabrication methods of AIEgen-based nanomaterials and their applications in in vitro/in vivo imaging, cell tracing, photodynamic therapy and drug delivery, focusing on the recent progress. Full article

(This article belongs to the Special Issue Aggregation-Induced Emission: Commemorative Issue in Honor of Professor Ben Zhong Tang’s Research Achievements on the Occasion of His 60th Birthday)

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17 pages, 1871 KiB

Open AccessFeature PaperReview

Taming the Notch Transcriptional Regulator for Cancer Therapy

by Luca Tamagnone^1,3,*

, Serena Zacchigna^2,4 and Michael Rehman^4,*

¹ Laboratory of Cancer Cell Biology, Candiolo Cancer Institute-FPO, IRCCS, Str. Prov. 142, 10060 Candiolo, TO, Italy

² Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy

³ Department of Oncology, University of Torino, c/o IRCCS, S.P. 142, 10060 Candiolo, TO, Italy

⁴ Cardiovascular Biology Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), 34149 Trieste, Italy

Molecules 2018, 23(2), 431; https://doi.org/10.3390/molecules23020431 - 15 Feb 2018

Cited by 40 | Viewed by 6997

Abstract

Notch signaling is a highly conserved pathway in all metazoans, which is deeply involved in the regulation of cell fate and differentiation, proliferation and migration during development. Research in the last decades has shown that the various components of the Notch signaling cascade [...] Read more.

Notch signaling is a highly conserved pathway in all metazoans, which is deeply involved in the regulation of cell fate and differentiation, proliferation and migration during development. Research in the last decades has shown that the various components of the Notch signaling cascade are either upregulated or activated in human cancers. Therefore, its downregulation stands as a promising and powerful strategy for cancer therapy. Here, we discuss the recent advances in the development of small molecule inhibitors, blocking antibodies and oligonucleotides that hinder Notch activity, and their outcome in clinical trials. Although Notch was initially identified as an oncogene, later studies showed that it can also act as a tumor suppressor in certain contexts. Further complexity is added by the existence of numerous Notch family members, which exert different activities and can be differentially targeted by inhibitors, potentially accounting for contradictory data on their therapeutic efficacy. Notably, recent evidence supports the rationale for combinatorial treatments including Notch inhibitors, which appear to be more effective than single agents in fighting cancer. Full article

(This article belongs to the Special Issue Transcription Factors as Therapeutic Targets)

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17 pages, 726 KiB

Open AccessReview

Food-Grade Encapsulation Systems for (−)-Epigallocatechin Gallate

by Meng Shi¹, Yun-Long Shi¹, Xu-Min Li¹

, Rui Yang¹, Zhuo-Yu Cai¹, Qing-Sheng Li¹, Shi-Cheng Ma², Jian-Hui Ye¹, Jian-Liang Lu¹, Yue-Rong Liang^1,*

and Xin-Qiang Zheng^1,*

¹ Tea Research Institute, Zhejiang University, Hangzhou 310058, China

² Liupao Tea Academy, Wuzhou 543003, China

Molecules 2018, 23(2), 445; https://doi.org/10.3390/molecules23020445 - 17 Feb 2018

Cited by 41 | Viewed by 5981

Abstract

(−)-Epigallocatechin gallate (EGCG) has attracted significant research interest due to its health-promoting effects such as antioxidation, anti-inflammation and anti-cancer activities. However, its instability and poor bioavailability have largely limited its efficacy and application. Food-grade materials such as proteins, carbohydrates and lipids show biodegradability, [...] Read more.

(−)-Epigallocatechin gallate (EGCG) has attracted significant research interest due to its health-promoting effects such as antioxidation, anti-inflammation and anti-cancer activities. However, its instability and poor bioavailability have largely limited its efficacy and application. Food-grade materials such as proteins, carbohydrates and lipids show biodegradability, biocompatibility and biofunctionality properties. Food-grade encapsulation systems are usually used to improve the bioavailability of EGCG. In the present paper, we provide an overview of materials and techniques used in encapsulating EGCG, in which the adsorption mechanisms of food-grade systems during in vitro digestion are reviewed. Moreover, the potential challenges and future work using food-grade encapsulates for delivering EGCG are also discussed. Full article

(This article belongs to the Special Issue Catechin in Human Health and Disease)

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7 pages, 492 KiB

Open AccessReview

Melatonin Regulates the Synthesis of Steroid Hormones on Male Reproduction: A Review

by Kun Yu^1,2,†, Shou-Long Deng^1,†, Tie-Cheng Sun¹, Yuan-Yuan Li¹ and Yi-Xun Liu^1,*

¹ State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China

² National Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China

^† These authors contributed equally to this work.

Molecules 2018, 23(2), 447; https://doi.org/10.3390/molecules23020447 - 17 Feb 2018

Cited by 76 | Viewed by 14809

Abstract

Melatonin is a ubiquitous molecule and exhibits different effects in long-day and short-day breeding animals. Testosterone, the main resource of androgens in the testis, is produced by Leydig cells but regulated mainly by cytokine secreted by Sertoli cells. Melatonin acts as a local [...] Read more.

Melatonin is a ubiquitous molecule and exhibits different effects in long-day and short-day breeding animals. Testosterone, the main resource of androgens in the testis, is produced by Leydig cells but regulated mainly by cytokine secreted by Sertoli cells. Melatonin acts as a local modulator of the endocrine activity in Leydig cells. In Sertoli cells, melatonin influences cellular proliferation and energy metabolism and, consequently, can regulate steroidogenesis. These suggest melatonin as a key player in the regulation of steroidogenesis. However, the melatonin-induced regulation of steroid hormones may differ among species, and the literature data indicate that melatonin has important effects on steroidogenesis and male reproduction. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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14 pages, 3851 KiB

Open AccessReview

Precision Aliphatic Polyesters via Segmer Assembly Polymerization

by Fu-Rong Zeng, Yang Liang and Zi-Long Li^*

Department of Chemistry, College of Science, Huazhong Agricultural University, Wuhan 430070, Hubei, China

Molecules 2018, 23(2), 452; https://doi.org/10.3390/molecules23020452 - 18 Feb 2018

Cited by 10 | Viewed by 5904

Abstract

Precise structure-property relation of a biodegradable polymer (e.g., aliphatic polyester) is anticipated only if monomer units and chiral centers are arranged in a defined primary sequence as a biomacromolecule. An emerging synthetic methodology, namely segmer assembly polymerization (SAP), is introduced in this paper [...] Read more.

Precise structure-property relation of a biodegradable polymer (e.g., aliphatic polyester) is anticipated only if monomer units and chiral centers are arranged in a defined primary sequence as a biomacromolecule. An emerging synthetic methodology, namely segmer assembly polymerization (SAP), is introduced in this paper to reveal the latest progress in polyester synthesis. Almost any periodic polyester envisioned can be synthesized via SAP using a programed linear or cyclic monomer. In this context, the macroscopic properties of a biodegradable polymer are fundamentally determined by microstructural information through a bottom-up approach. It can be highlighted that SAP ideally combines the precision of organic synthesis and the high efficiency of a polymerization reaction. Previously reported strategies including nucleophilic displacement, polyesterification, cross-metathesis polymerization (CMP), ring-opening polymerization (ROP), ring-opening metathesis polymerization (ROMP) and entropy-driven ring-opening metathesis polymerization (ED-ROMP) are critically reviewed in this paper to shed light on precision synthesis of aliphatic polyesters via SAP. Emerging yet challenging, SAP is a paradigm which reflects the convergence of organic and polymer chemistries and is also an efficient pathway to microstructural control. The current status, future challenges and promising trends in this realm are analyzed and discussed in this overview of the state-of-the-art. Full article

(This article belongs to the Special Issue Advances in Biodegradable Polymers)

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21 pages, 8166 KiB

Open AccessFeature PaperReview

Radical Polymerization of Alkyl 2-Cyanoacrylates

by Cormac Duffy^1,2, Per B. Zetterlund³ and Fawaz Aldabbagh^2,4,*

¹ Henkel Ireland Operations & Research Limited, Whitestown, Dublin 24, Ireland

² School of Chemistry, National University of Ireland Galway, University Road, Galway H91 TK33, Ireland

³ Centre for Advanced Macromolecular Design (CAMD), School of Chemical Engineering, The University of New South Wales, Sydney, NSW 2052, Australia

⁴ Present address: Department of Pharmacy, School of Life Sciences, Pharmacy & Chemistry, Kingston University, Penrhyn Road, Kingston upon Thames KT1 2EE, UK

Molecules 2018, 23(2), 465; https://doi.org/10.3390/molecules23020465 - 20 Feb 2018

Cited by 44 | Viewed by 11288

Abstract

Cyanoacrylates (CAs) are well-known fast-setting adhesives, which are sold as liquids in the presence of stabilizers. Rapid anionic polymerization on exposure to surface moisture is responsible for instant adhesion. The more difficult, but synthetically more useful radical polymerization is only possible under acidic [...] Read more.

Cyanoacrylates (CAs) are well-known fast-setting adhesives, which are sold as liquids in the presence of stabilizers. Rapid anionic polymerization on exposure to surface moisture is responsible for instant adhesion. The more difficult, but synthetically more useful radical polymerization is only possible under acidic conditions. Recommendations on the handling of CAs and the resulting polymers are provided herein. In this review article, after a general description of monomer and polymer properties, radical homo- and copolymerization studies are described, along with an overview of nanoparticle preparations. A summary of our recently reported radical polymerization of CAs, using reversible addition-fragmentation chain transfer (RAFT) polymerization, is provided. Full article

(This article belongs to the Special Issue Radical Chemistry)

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16 pages, 2519 KiB

Open AccessReview

Therapeutic Potential of Oridonin and Its Analogs: From Anticancer and Antiinflammation to Neuroprotection

by Jimin Xu¹

, Eric A. Wold¹

, Ye Ding¹, Qiang Shen²

and Jia Zhou^1,*

¹ Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA

² Department of Clinical Cancer Prevention, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

Molecules 2018, 23(2), 474; https://doi.org/10.3390/molecules23020474 - 22 Feb 2018

Cited by 100 | Viewed by 6909

Abstract

Oridonin, a diterpenoid natural product commonly used in East Asian herbal medicine, is garnering increased attention in the biomedical community due to its extensive biological activities that include antitumor, anti-inflammatory, antimicrobial, hepatic fibrosis prevention, and neurological effects. Over the past decade, significant progress [...] Read more.

Oridonin, a diterpenoid natural product commonly used in East Asian herbal medicine, is garnering increased attention in the biomedical community due to its extensive biological activities that include antitumor, anti-inflammatory, antimicrobial, hepatic fibrosis prevention, and neurological effects. Over the past decade, significant progress has been made in structure activity relationship and mechanism of action studies of oridonin for the treatment of cancer and other diseases. This review provides a brief summary on oridonin and its analogs in cancer drug discovery and antiinflammation and highlights its emerging therapeutic potential in neuroprotection applications. Full article

(This article belongs to the Special Issue Neuroprotective Agents)

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11 pages, 760 KiB

Open AccessReview

Sulphated Flavonoids: Biosynthesis, Structures, and Biological Activities

by Yanna C. F. Teles¹

, Maria Sallett R. Souza² and Maria De Fátima Vanderlei de Souza^2,3,*

¹ Department of Chemistry and Physics, Agrarian Sciences Center, Universidade Federal da Paraíba, Areia 58397-000, PB, Brazil

² Post graduation Program in Bioactive Natural and Synthetic Products, Health Sciences Center, Universidade Federal da Paraíba, João Pessoa 58051-900, PB, Brazil

³ Post graduation in Development and Technological Innovation in Medicines, Health Sciences Center, Universidade Federal da Paraíba, João Pessoa 58051-900, PB, Brazil

Molecules 2018, 23(2), 480; https://doi.org/10.3390/molecules23020480 - 23 Feb 2018

Cited by 107 | Viewed by 8551

Abstract

The great diversity of enzymatic reactions in plant secondary metabolism allows the continuous discovery of new natural compounds and derivatives. Flavonoids, for example, can be found as aglycone or as several sorts of glycosylated, acetylated, methylated, and sulphated derivatives. This review focuses on [...] Read more.

The great diversity of enzymatic reactions in plant secondary metabolism allows the continuous discovery of new natural compounds and derivatives. Flavonoids, for example, can be found as aglycone or as several sorts of glycosylated, acetylated, methylated, and sulphated derivatives. This review focuses on sulphated flavonoids, an uncommon group of flavonoid derivatives found in some plant families. This work presents a compilation of sulphated flavonoids and their natural sources reported in the literature. Biosynthetic aspects and biological activities have also been reviewed, showing that these particular kinds of natural compounds play an interesting role in plant metabolism, as well as being potential candidates for the development of new drugs. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

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18 pages, 3775 KiB

Open AccessFeature PaperReview

Enantiomeric Mixtures in Natural Product Chemistry: Separation and Absolute Configuration Assignment

by Andrea N. L. Batista¹

, Fernando M. dos Santos¹, João M. Batista^1,2,* and Quezia B. Cass^1,*

¹ Department of Chemistry, Federal University of São Carlos—UFSCar, Rod. Washington Luis s/n, km 235, São Carlos, SP 13565-905, Brazil

² Institute of Science and Technology, Federal University of São Paulo—UNIFESP, R. Talim 330, São José dos Campos, SP 12231-280, Brazil

Molecules 2018, 23(2), 492; https://doi.org/10.3390/molecules23020492 - 23 Feb 2018

Cited by 52 | Viewed by 9476

Abstract

Chiral natural product molecules are generally assumed to be biosynthesized in an enantiomerically pure or enriched fashion. Nevertheless, a significant amount of racemates or enantiomerically enriched mixtures has been reported from natural sources. This number is estimated to be even larger since the [...] Read more.

Chiral natural product molecules are generally assumed to be biosynthesized in an enantiomerically pure or enriched fashion. Nevertheless, a significant amount of racemates or enantiomerically enriched mixtures has been reported from natural sources. This number is estimated to be even larger since the enantiomeric purity of secondary metabolites is rarely checked in the natural product isolation pipeline. This latter fact may have drastic effects on the evaluation of the biological activity of chiral natural products. A second bottleneck is the determination of their absolute configurations. Despite the widespread use of optical rotation and electronic circular dichroism, most of the stereochemical assignments are based on empirical correlations with similar compounds reported in the literature. As an alternative, the combination of vibrational circular dichroism and quantum chemical calculations has emerged as a powerful and reliable tool for both conformational and configurational analysis of natural products, even for those lacking UV-Vis chromophores. In this review, we aim to provide the reader with a critical overview of the occurrence of enantiomeric mixtures of secondary metabolites in nature as well the best practices for their detection, enantioselective separation using liquid chromatography, and determination of absolute configuration by means of vibrational circular dichroism and density functional theory calculations. Full article

(This article belongs to the Special Issue Chirality in Health and Environment: Recent developments)

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19 pages, 1793 KiB

Open AccessReview

Natural Alkaloids and Heterocycles as G-Quadruplex Ligands and Potential Anticancer Agents

by Tong Che, Yu-Qing Wang, Zhou-Li Huang, Jia-Heng Tan, Zhi-Shu Huang and Shuo-Bin Chen^*

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China

Molecules 2018, 23(2), 493; https://doi.org/10.3390/molecules23020493 - 23 Feb 2018

Cited by 44 | Viewed by 6654

Abstract

G-quadruplexes are four-stranded nucleic acid secondary structures that are formed in guanine-rich sequences. G-quadruplexes are widely distributed in functional regions of the human genome and transcriptome, such as human telomeres, oncogene promoter regions, replication initiation sites, and untranslated regions. Many G-quadruplex-forming sequences are [...] Read more.

G-quadruplexes are four-stranded nucleic acid secondary structures that are formed in guanine-rich sequences. G-quadruplexes are widely distributed in functional regions of the human genome and transcriptome, such as human telomeres, oncogene promoter regions, replication initiation sites, and untranslated regions. Many G-quadruplex-forming sequences are found to be associated with cancer, and thus, these non-canonical nucleic acid structures are considered to be attractive molecular targets for cancer therapeutics with novel mechanisms of action. In this mini review, we summarize recent advances made by our lab in the study of G-quadruplex-targeted natural alkaloids and their derivatives toward the development of potential anticancer agents. Full article

(This article belongs to the Special Issue G-Quadruplex Ligands and Cancer)

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25 pages, 3895 KiB

Open AccessReview

Mitochondria: Central Organelles for Melatonin′s Antioxidant and Anti-Aging Actions

by Russel J. Reiter^1,*, Dun Xian Tan¹, Sergio Rosales-Corral², Annia Galano³

, Xin Jia Zhou¹ and Bing Xu¹

¹ Department of Cellular and Structural Biology UT Health San Antonio, San Antonio, SD 78229, USA

² Centro de Investigacion Biomedica de Occidente, Instituo Mexicana del Seguro Social, Guadalajara 44346, Mexico

³ Departamento de Quimica, Universidad Autonoma Metropolitana-Iztapatapa, Mexico D.F. 09340, Mexico

Molecules 2018, 23(2), 509; https://doi.org/10.3390/molecules23020509 - 24 Feb 2018

Cited by 282 | Viewed by 24487

Abstract

Melatonin, along with its metabolites, have long been known to significantly reduce the oxidative stress burden of aging cells or cells exposed to toxins. Oxidative damage is a result of free radicals produced in cells, especially in mitochondria. When measured, melatonin, a potent [...] Read more.

Melatonin, along with its metabolites, have long been known to significantly reduce the oxidative stress burden of aging cells or cells exposed to toxins. Oxidative damage is a result of free radicals produced in cells, especially in mitochondria. When measured, melatonin, a potent antioxidant, was found to be in higher concentrations in mitochondria than in other organelles or subcellular locations. Recent evidence indicates that mitochondrial membranes possess transporters that aid in the rapid uptake of melatonin by these organelles against a gradient. Moreover, we predicted several years ago that, because of their origin from melatonin-producing bacteria, mitochondria likely also synthesize melatonin. Data accumulated within the last year supports this prediction. A high content of melatonin in mitochondria would be fortuitous, since these organelles produce an abundance of free radicals. Thus, melatonin is optimally positioned to scavenge the radicals and reduce the degree of oxidative damage. In light of the “free radical theory of aging”, including all of its iterations, high melatonin levels in mitochondria would be expected to protect against age-related organismal decline. Also, there are many age-associated diseases that have, as a contributing factor, free radical damage. These multiple diseases may likely be deferred in their onset or progression if mitochondrial levels of melatonin can be maintained into advanced age. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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