Molecules

Editorial

Jump to: Research, Review, Other

2 pages, 137 KiB

Open AccessEditorial

Special Issue “Membrane Catalysis”

by Raffaele Molinari

Department of Environmental and Chemical Engineering, Università della Calabria, 87036 Rende (CS), Italy

Molecules 2016, 21(7), 851; https://doi.org/10.3390/molecules21070851 - 28 Jun 2016

Cited by 1 | Viewed by 4658

Abstract

Membrane technology is recognized as a scientiﬁc sector of multidisciplinary interest.[...] Full article

(This article belongs to the Special Issue Membrane Catalysis)

3 pages, 339 KiB

Open AccessEditorial

Foreword: Pacific Fragments

by Daniel A. Erlanson

Carmot Therapeutics Inc., 409 Illinois Street, San Francisco, CA 94158, USA

Molecules 2016, 21(7), 926; https://doi.org/10.3390/molecules21070926 - 16 Jul 2016

Viewed by 4101

Abstract

Pacific, which is derived from the Latin pac, means peaceful. [...] Full article

(This article belongs to the Special Issue Developments in Fragment-Based Lead Discovery)

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Research

Jump to: Editorial, Review, Other

8 pages, 1215 KiB

Open AccessArticle

Synthesis and Evaluation of Novel α-Aminoamides Containing an Indole Moiety for the Treatment of Neuropathic Pain

by Haotian Li, Shiyong Fan, Jingchao Cheng, Ping Zhang, Bohua Zhong^* and Weiguo Shi^*

Beijing Institute of Pharmacology & Toxicology, 27 Tai-Ping Road, Beijing 100850, China

Molecules 2016, 21(7), 793; https://doi.org/10.3390/molecules21070793 - 23 Jun 2016

Cited by 6 | Viewed by 5889

Abstract

The α-aminoamide family of sodium ion channel blockers have exhibited analgesic effects on neuropathic pain. Here, a series of novel α-aminoamides containing an indole ring were designed and synthesized. These compounds were evaluated in mice using a formalin test and they exhibited significant [...] Read more.

The α-aminoamide family of sodium ion channel blockers have exhibited analgesic effects on neuropathic pain. Here, a series of novel α-aminoamides containing an indole ring were designed and synthesized. These compounds were evaluated in mice using a formalin test and they exhibited significant anti-allodynia activities. However, the analgesic mechanism of these compounds remains unclear; a subset of the synthesized compounds can only moderately inhibit the sodium ion channel, Nav1.7, in a whole-cell patch clamp assay. Overall, these results suggest that introduction of an indole moiety to α-aminoamide derivatives can significantly improve their bioactivity and further study is warranted. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 3662 KiB

Open AccessArticle

Spectroscopic and Kinetic Characterization of Peroxidase-Like π-Cation Radical Pinch-Porphyrin-Iron(III) Reaction Intermediate Models of Peroxidase Enzymes

by Samuel Hernández Anzaldo¹

, Uriel Arroyo Abad¹, Armando León García¹, Daniel Ramírez Rosales²

, Rafael Zamorano Ulloa² and Yasmi Reyes Ortega^1,*

¹ Centro de Química Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla. Edificio 103H, Ciudad Universitaria, Col. Jardines de San Manuel, Puebla, Pue. 72570, Mexico

² Instituto Politécnico Nacional, ESFM, Ave. Instituto Politécnico Nacional S/N, Edif. 9 U.P. Zacatenco, Col. San Pedro Zacatenco, México City 07738, Mexico

Molecules 2016, 21(7), 804; https://doi.org/10.3390/molecules21070804 - 27 Jun 2016

Cited by 6 | Viewed by 7197

Abstract

The spectroscopic and kinetic characterization of two intermediates from the H₂O₂ oxidation of three dimethyl ester [(proto), (meso), (deuteroporphyrinato) (picdien)]Fe(III) complexes ([FePPPic], [FeMPPic] and [FeDPPic], respectively) pinch-porphyrin peroxidase enzyme models, with s = 5/2 and 3/2 Fe(III) quantum mixed spin [...] Read more.

The spectroscopic and kinetic characterization of two intermediates from the H₂O₂ oxidation of three dimethyl ester [(proto), (meso), (deuteroporphyrinato) (picdien)]Fe(III) complexes ([FePPPic], [FeMPPic] and [FeDPPic], respectively) pinch-porphyrin peroxidase enzyme models, with s = 5/2 and 3/2 Fe(III) quantum mixed spin (qms) ground states is described herein. The kinetic study by UV/Vis at λ_max = 465 nm showed two different types of kinetics during the oxidation process in the guaiacol test for peroxidases (1–3 + guaiacol + H₂O₂ → oxidation guaiacol products). The first intermediate was observed during the first 24 s of the reaction. When the reaction conditions were changed to higher concentration of pinch-porphyrins and hydrogen peroxide only one type of kinetics was observed. Next, the reaction was performed only between pinch-porphyrins-Fe(III) and H₂O₂, resulting in only two types of kinetics that were developed during the first 0–4 s. After this time a self-oxidation process was observed. Our hypotheses state that the formation of the π-cation radicals, reaction intermediates of the pinch-porphyrin-Fe(III) family with the ligand picdien [N,N’-bis-pyridin-2-ylmethyl-propane-1,3-diamine], occurred with unique kinetics that are different from the overall process and was involved in the oxidation pathway. UV-Vis, ¹H-NMR and ESR spectra confirmed the formation of such intermediates. The results in this paper highlight the link between different spectroscopic techniques that positively depict the kinetic traits of artificial compounds with enzyme-like activity. Full article

(This article belongs to the Special Issue Biomolecules Modification)

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14 pages, 2075 KiB

Open AccessArticle

Extraction of Flavonoids from the Flowers of Abelmoschus manihot (L.) Medic by Modified Supercritical CO₂ Extraction and Determination of Antioxidant and Anti-Adipogenic Activity

by Jingjing Li^1,2, Juan Zhang^1,* and Min Wang^1,*

¹ School of Life Science and Technology, China Pharmaceutical University, #24 Tong Jia Xiang, Nanjing 210009, China

² Department of Pharmaceutical Engineering, Zhejiang Pharmaceutical College, #888 Yin Xian Avenue Eastern Section, Ningbo 315000, China

Molecules 2016, 21(7), 810; https://doi.org/10.3390/molecules21070810 - 25 Jun 2016

Cited by 31 | Viewed by 8073

Abstract

Abelmoschus manihot (L.) Medic has been used for many years in Chinese traditional medicine. In this study, supercritical CO₂ plus a modifier was utilized to extract flavonoids from the flowers of Abelmoschus manihot (L.) Medic. The effects of temperature (40 °C–60 °C), [...] Read more.

Abelmoschus manihot (L.) Medic has been used for many years in Chinese traditional medicine. In this study, supercritical CO₂ plus a modifier was utilized to extract flavonoids from the flowers of Abelmoschus manihot (L.) Medic. The effects of temperature (40 °C–60 °C), pressure (10–30 MPa) and different concentrations of ethanol as modifier (60%–90%, ethanol:water, v/v) on major flavonol content and the antioxidant activity of the extracts were studied by response surface methodology (RSM) using a Box-Behnken design. The flavonol content was calculated as the sum of the concentrations of seven major flavonoids, namely rutin, hyperin, isoquercetin, hibifolin, myricetin, quercetin-3′-O-glucoside and quercetin, which were simultaneously determined by a HPLC method. The antioxidant activity was evaluated by a 2,2-diphenyl-1-picrylhydarzyl (DPPH) free radical-scavenging assay. The results showed that three factors and their interactions could be well fitted to second-order polynomial models (p < 0.05). At the optimal extraction conditions for flavonol content (20 MPa, 52 °C, and 85% ethanol content), the yield of flavonoids was 41.96 mg/g and the IC₅₀ value was 0.288 mg/mL, respectively, suggesting the extract has high antioxidant activity. Furthermore, the anti-adipogenic activity of the extract on the 3T3-L1 cell line was investigated. The results indicated that it can downregulate PPARγ and C/EBPα expression at mRNA. In summary, in this study, we have established a cost-effective method for the extraction of flavonoids from the flowers of Abelmoschus manihot (L.) Medic using supercritical fluid extraction and the extracts exhibited potent antioxidant and anti-adipogenic effects, suggesting a possible therapeutic approach for the prevention and treatment of obesity. Full article

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10 pages, 903 KiB

Open AccessArticle

On Topological Indices of Certain Families of Nanostar Dendrimers

by Mohamad Nazri Husin¹, Roslan Hasni^1,*, Nabeel Ezzulddin Arif² and Muhammad Imran³

¹ School of Informatics and Applied Mathematics, University Malaysia Terengganu, Kuala Terengganu, Terengganu 21030, Malaysia

² Department of Mathematics, College of Computer Sciences and Mathematics, Tikrit University, Tikrit 34001, Iraq

³ Department of Mathematics, School of Natural Sciences, National University of Sciences and Technology, Sector H-12, Islamabad 44000, Pakistan

Molecules 2016, 21(7), 821; https://doi.org/10.3390/molecules21070821 - 24 Jun 2016

Cited by 43 | Viewed by 7044

Abstract

A topological index of graph G is a numerical parameter related to G which characterizes its molecular topology and is usually graph invariant. In the field of quantitative structure-activity (QSAR)/quantitative structure-activity structure-property (QSPR) research, theoretical properties of the chemical compounds and their molecular [...] Read more.

A topological index of graph G is a numerical parameter related to G which characterizes its molecular topology and is usually graph invariant. In the field of quantitative structure-activity (QSAR)/quantitative structure-activity structure-property (QSPR) research, theoretical properties of the chemical compounds and their molecular topological indices such as the Randić connectivity index, atom-bond connectivity (ABC) index and geometric-arithmetic (GA) index are used to predict the bioactivity of different chemical compounds. A dendrimer is an artificially manufactured or synthesized molecule built up from the branched units called monomers. In this paper, the fourth version of ABC index and the fifth version of GA index of certain families of nanostar dendrimers are investigated. We derive the analytical closed formulas for these families of nanostar dendrimers. The obtained results can be of use in molecular data mining, particularly in researching the uniqueness of tested (hyper-branched) molecular graphs. Full article

(This article belongs to the Special Issue Functional Dendrimers)

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22 pages, 3958 KiB

Open AccessArticle

Computational Evaluation of Nucleotide Insertion Opposite Expanded and Widened DNA by the Translesion Synthesis Polymerase Dpo4

by Laura Albrecht^†, Katie A. Wilson^† and Stacey D. Wetmore^*

¹ Department of Chemistry and Biochemistry, University of Lethbridge, 4401 University Drive West, Lethbridge Alberta, AB T1K 3M4, Canada

^† These authors contributed equally to this work.

Molecules 2016, 21(7), 822; https://doi.org/10.3390/molecules21070822 - 23 Jun 2016

Cited by 2 | Viewed by 7526

Abstract

Expanded (x) and widened (y) deoxyribose nucleic acids (DNA) have an extra benzene ring incorporated either horizontally (xDNA) or vertically (yDNA) between a natural pyrimidine base and the deoxyribose, or between the 5- and 6-membered rings of a natural purine. Far-reaching applications for [...] Read more.

Expanded (x) and widened (y) deoxyribose nucleic acids (DNA) have an extra benzene ring incorporated either horizontally (xDNA) or vertically (yDNA) between a natural pyrimidine base and the deoxyribose, or between the 5- and 6-membered rings of a natural purine. Far-reaching applications for (x,y)DNA include nucleic acid probes and extending the natural genetic code. Since modified nucleobases must encode information that can be passed to the next generation in order to be a useful extension of the genetic code, the ability of translesion (bypass) polymerases to replicate modified bases is an active area of research. The common model bypass polymerase DNA polymerase IV (Dpo4) has been previously shown to successfully replicate and extend past a single modified nucleobase on a template DNA strand. In the current study, molecular dynamics (MD) simulations are used to evaluate the accommodation of expanded/widened nucleobases in the Dpo4 active site, providing the first structural information on the replication of (x,y)DNA. Our results indicate that the Dpo4 catalytic (palm) domain is not significantly impacted by the (x,y)DNA bases. Instead, the template strand is displaced to accommodate the increased C1’–C1’ base-pair distance. The structural insights unveiled in the present work not only increase our fundamental understanding of Dpo4 replication, but also reveal the process by which Dpo4 replicates (x,y)DNA, and thereby will contribute to the optimization of high fidelity and efficient polymerases for the replication of modified nucleobases. Full article

(This article belongs to the Special Issue Computational Design: A New Approach to Drug and Molecular Discovery)

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21 pages, 17125 KiB

Open AccessArticle

Identification of the Structural Features of Guanine Derivatives as MGMT Inhibitors Using 3D-QSAR Modeling Combined with Molecular Docking

by Guohui Sun^†

, Tengjiao Fan^†, Na Zhang, Ting Ren, Lijiao Zhao^*

and Rugang Zhong

¹ Beijing Key Laboratory of Environmental & Viral Oncology, College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China

^† These authors contributed equally to this work.

Molecules 2016, 21(7), 823; https://doi.org/10.3390/molecules21070823 - 23 Jun 2016

Cited by 22 | Viewed by 6475

Abstract

DNA repair enzyme O⁶-methylguanine-DNA methyltransferase (MGMT), which plays an important role in inducing drug resistance against alkylating agents that modify the O⁶ position of guanine in DNA, is an attractive target for anti-tumor chemotherapy. A series of MGMT inhibitors have [...] Read more.

DNA repair enzyme O⁶-methylguanine-DNA methyltransferase (MGMT), which plays an important role in inducing drug resistance against alkylating agents that modify the O⁶ position of guanine in DNA, is an attractive target for anti-tumor chemotherapy. A series of MGMT inhibitors have been synthesized over the past decades to improve the chemotherapeutic effects of O⁶-alkylating agents. In the present study, we performed a three-dimensional quantitative structure activity relationship (3D-QSAR) study on 97 guanine derivatives as MGMT inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. Three different alignment methods (ligand-based, DFT optimization-based and docking-based alignment) were employed to develop reliable 3D-QSAR models. Statistical parameters derived from the models using the above three alignment methods showed that the ligand-based CoMFA (Q_cv² = 0.672 and R_ncv² = 0.997) and CoMSIA (Q_cv² = 0.703 and R_ncv² = 0.946) models were better than the other two alignment methods-based CoMFA and CoMSIA models. The two ligand-based models were further confirmed by an external test-set validation and a Y-randomization examination. The ligand-based CoMFA model (Q_ext² = 0.691, R_pred² = 0.738 and slope k = 0.91) was observed with acceptable external test-set validation values rather than the CoMSIA model (Q_ext² = 0.307, R_pred² = 0.4 and slope k = 0.719). Docking studies were carried out to predict the binding modes of the inhibitors with MGMT. The results indicated that the obtained binding interactions were consistent with the 3D contour maps. Overall, the combined results of the 3D-QSAR and the docking obtained in this study provide an insight into the understanding of the interactions between guanine derivatives and MGMT protein, which will assist in designing novel MGMT inhibitors with desired activity. Full article

(This article belongs to the Special Issue Computational Design: A New Approach to Drug and Molecular Discovery)

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17 pages, 4458 KiB

Open AccessArticle

Activating and Attenuating the Amicoumacin Antibiotics

by Hyun Bong Park^1,2

, Corey E. Perez^1,2

, Elena Kim Perry^2,3 and Jason M. Crawford^1,2,4,*

¹ Department of Chemistry, Yale University, New Haven, CT 06520, USA

² Chemical Biology Institute, Yale University, West Haven, CT 06516, USA

³ Department of Ecology & Evolutionary Biology, Yale University, New Haven, CT 06520, USA

⁴ Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06536, USA

Molecules 2016, 21(7), 824; https://doi.org/10.3390/molecules21070824 - 24 Jun 2016

Cited by 44 | Viewed by 11088

Abstract

The amicoumacins belong to a class of dihydroisocoumarin natural products and display antibacterial, antifungal, anticancer, and anti-inflammatory activities. Amicoumacins are the pro-drug activation products of a bacterial nonribosomal peptide-polyketide hybrid biosynthetic pathway and have been isolated from Gram-positive Bacillus and Nocardia species. Here, [...] Read more.

The amicoumacins belong to a class of dihydroisocoumarin natural products and display antibacterial, antifungal, anticancer, and anti-inflammatory activities. Amicoumacins are the pro-drug activation products of a bacterial nonribosomal peptide-polyketide hybrid biosynthetic pathway and have been isolated from Gram-positive Bacillus and Nocardia species. Here, we report the stimulation of a “cryptic” amicoumacin pathway in the entomopathogenic Gram-negative bacterium Xenorhabdus bovienii, a strain not previously known to produce amicoumacins. X. bovienii participates in a multi-lateral symbiosis where it is pathogenic to insects and mutualistic to its Steinernema nematode host. Waxmoth larvae are common prey of the X. bovienii-Steinernema pair. Employing a medium designed to mimic the amino acid content of the waxmoth circulatory fluid led to the detection and characterization of amicoumacins in X. bovienii. The chemical structures of the amicoumacins were supported by 2D-NMR, HR-ESI-QTOF-MS, tandem MS, and polarimeter spectral data. A comparative gene cluster analysis of the identified X. bovienii amicoumacin pathway to that of the Bacillus subtilis amicoumacin pathway and the structurally-related Xenorhabdus nematophila xenocoumacin pathway is presented. The X. bovienii pathway encodes an acetyltransferase not found in the other reported pathways, which leads to a series of N-acetyl-amicoumacins that lack antibacterial activity. N-acetylation of amicoumacin was validated through in vitro protein biochemical studies, and the impact of N-acylation on amicoumacin’s mode of action was examined through ribosomal structural analyses. Full article

(This article belongs to the Special Issue Biosynthesis of Natural Products)

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14 pages, 1006 KiB

Open AccessArticle

Novel (E)-β-Farnesene Analogues Containing 2-Nitroiminohexahydro-1,3,5-triazine: Synthesis and Biological Activity Evaluation

by Yaoguo Qin¹, Jingpeng Zhang¹, Dunlun Song², Hongxia Duan¹, Wenhao Li¹ and Xinling Yang^1,*

¹ Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China

² Department of Entomology, College of Plant Protection, China Agricultural University, Beijing 100193, China

Molecules 2016, 21(7), 825; https://doi.org/10.3390/molecules21070825 - 24 Jun 2016

Cited by 20 | Viewed by 6814

Abstract

In order to discover novel eco-friendly compounds with good activity for aphid control, (E)-β-farnesene (EβF), the main component of the aphid alarm pheromone, was chosen as the lead compound. By introducing a 2-nitroimino-hexahydro-1,3,5-triazine moiety (abbreviated NHT) to replace the unstable conjugated [...] Read more.

In order to discover novel eco-friendly compounds with good activity for aphid control, (E)-β-farnesene (EβF), the main component of the aphid alarm pheromone, was chosen as the lead compound. By introducing a 2-nitroimino-hexahydro-1,3,5-triazine moiety (abbreviated NHT) to replace the unstable conjugated double bond system of EβF, a series of novel EβF analogues containing the NHT moiety were synthesized via the reaction of substituted NHT rings with (E)-1-chloro-3,7-dimethylocta-2,6-diene. All the compounds were characterized by ¹H-NMR, ¹³C-NMR, IR, and high resolution mass spectroscopy (HRMS). The bioassay results showed that all the analogues displayed different repellent and aphicidal activities against green peach aphid (Myzus persicae). Particularly, the analogue 4r exhibited obvious repellent activity (repellent proportion: 78.43%) and similar aphicidal activity against M. persicae (mortality: 82.05%) as the commercial compound pymetrozine (80.07%). A preliminary structure-activity relationship (SAR) study was also performed, which offered valuable clues for the design of further new EβF analogues. Full article

(This article belongs to the Special Issue Drug Design and Discovery: Principles and Applications)

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11 pages, 6782 KiB

Open AccessArticle

Dual Behavior of Iodine Species in Condensation of Anilines and Vinyl Ethers Affording 2-Methylquinolines

by Song Thi Le¹, Chisa Yasuoka², Haruyasu Asahara^2,3,*

and Nagatoshi Nishiwaki^2,3,*

¹ Faculty of Applied Sciences, Ton Duc Thang University, 19 Nguyen Huu Tho Street, Tan Phong Ward, District 7, Ho Chi Minh City 700000, Vietnam

² School of Environmental Science and Technology, Kochi University of Technology, Tosayamada, Kami, Kochi 782-8502, Japan

³ Research Center for Material Science and Engineering, Kochi University of Technology, Tosayamada, Kami, Kochi 782-8502, Japan

Molecules 2016, 21(7), 827; https://doi.org/10.3390/molecules21070827 - 25 Jun 2016

Cited by 7 | Viewed by 8184

Abstract

A metal-free, mild and efficient method for the synthesis of 2-methylquinolines was successfully developed by condensation of anilines with vinyl ethers in the presence of catalytic amount of iodine. Modification of both pyridine and benzene moieties was easily achieved by changing only the [...] Read more.

A metal-free, mild and efficient method for the synthesis of 2-methylquinolines was successfully developed by condensation of anilines with vinyl ethers in the presence of catalytic amount of iodine. Modification of both pyridine and benzene moieties was easily achieved by changing only the vinyl ether and aniline. In this reaction, the iodine species was revealed to show dual behavior; molecular iodine serves as an oxidant, while its reduced form, hydrogen iodide, activates the vinyl ether. The redox reaction between these iodine species enables the use of a catalytic amount of iodine in this synthetic method. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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16 pages, 5516 KiB

Open AccessArticle

Synthesis, Fungicidal Activity and Mode of Action of 4-Phenyl-6-trifluoromethyl-2-aminopyrimidines against Botrytis cinerea

by Chunhui Liu¹, Zining Cui^2,*, Xiaojing Yan³, Zhiqiu Qi¹, Mingshan Ji¹ and Xinghai Li^1,*

¹ Department of Pesticide Science, Plant Protection College, Shenyang Agricultural University, Shenyang 110866, Liaoning, China

² State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Integrative Microbiology Research Centre, Guangdong Province Key Laboratory of Microbial Signals and Disease Control, South China Agricultural University, Guangzhou 510642, China

³ Key Laboratory of Integrated Pest Management in Crops, Ministry of Agriculture, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China

Molecules 2016, 21(7), 828; https://doi.org/10.3390/molecules21070828 - 24 Jun 2016

Cited by 20 | Viewed by 7669

Abstract

Anilinopyrimidines are the main chemical agents for management of Botrytis cinerea. However, the drug resistance in fungi against this kind of compounds is very serious. To explore new potential fungicides against B. cinerea, a series of 4-phenyl-6-trifluoromethyl-2-amino-pyrimidine compounds (compounds III-1 to [...] Read more.

Anilinopyrimidines are the main chemical agents for management of Botrytis cinerea. However, the drug resistance in fungi against this kind of compounds is very serious. To explore new potential fungicides against B. cinerea, a series of 4-phenyl-6-trifluoromethyl-2-amino-pyrimidine compounds (compounds III-1 to III-22) were synthesized, and their structures were confirmed by ¹H-NMR, IR and MS. Most of these compounds possessed excellent fungicidal activity. The compounds III-3 and III-13 showed higher fungicidal activity than the positive control pyrimethanil on fructose gelatin agar (FGA), and compound III-3 on potato dextrose agar (PDA) indicated high activity compared to the positive control cyprodinil. In vivo greenhouse results indicated that the activity of compounds III-3, III-8, and III-11 was significantly higher than that of the fungicide pyrimethanil. Scanning electron micrography (SEM) and transmission electron micrography (TEM) were applied to illustrate the mechanism of title compounds against B. cinerea. The title compounds, especially those containing a fluorine atom at the ortho-position on the benzene ring, could maintain the antifungal activity against B. cinerea, but their mechanism of action is different from that of cyprodinil. The present study lays a good foundation for us to find more efficient reagents against B. cinerea. Full article

(This article belongs to the Section Organic Chemistry)

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14 pages, 4005 KiB

Open AccessArticle

Location and Effects of an Antitumoral Catechin on the Structural Properties of Phosphatidylethanolamine Membranes

by Francisco Casado¹, José A. Teruel¹, Santiago Casado²

, Antonio Ortiz¹, José N. Rodríguez-López¹ and Francisco J. Aranda^1,*

¹ Departamento de Bioquímica y Biología Molecular-A, Universidad de Murcia, Campus de Espinardo, Murcia E-30100, Spain

² IMDEA-Nanoscience, Campus de Cantoblanco, Madrid E-28049, Spain

Molecules 2016, 21(7), 829; https://doi.org/10.3390/molecules21070829 - 24 Jun 2016

Cited by 6 | Viewed by 6200

Abstract

Green tea catechins exhibit high diversity of biological effects including antioncogenic properties, and there is enormous interest in their potential use in the treatment of a number of pathologies. It is recognized that the mechanism underlying the activity of catechins relay in part [...] Read more.

Green tea catechins exhibit high diversity of biological effects including antioncogenic properties, and there is enormous interest in their potential use in the treatment of a number of pathologies. It is recognized that the mechanism underlying the activity of catechins relay in part in processes related to the membrane, and many studies revealed that the ability of catechins to interact with lipids plays a probably necessary role in their mechanism of action. We present in this work the characterization of the interaction between an antitumoral synthetically modified catechin (3-O-(3,4,5-trimethoxybenzoyl)-(−)-catechin, TMCG) and dimiristoylphosphatidyl-ethanolamine (DMPE) membranes using an array of biophysical techniques which include differential scanning calorimetry, X-ray diffraction, infrared spectroscopy, atomic force microscopy, and molecular dynamics simulations. We found that TMCG incorporate into DMPE bilayers perturbing the thermotropic transition from the gel to the fluid state forming enriched domains which separated into different gel phases. TMCG does not influence the overall bilayer assembly of phosphatidylethanolamine systems but it manages to influence the interfacial region of the membrane and slightly decrease the interlamellar repeat distance of the bilayer. TMCG seems to be located in the interior of the phosphatidylethanolamine bilayer with the methoxy groups being in the deepest position and some portion of the molecule interacting with the water interface. We believe that the reported interactions are significant not only from the point of view of the known antitumoral effect of TMCG, but also might contribute to understanding the basic molecular mechanism of the biological effects of the catechins found at the membrane level. Full article

(This article belongs to the Special Issue Catechins and Human Health: Current State of the Science)

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15 pages, 471 KiB

Open AccessArticle

Chemical Profile, Antioxidant and Antibacterial Activities of Achillea moschata Wulfen, an Endemic Species from the Alps

by Sara Vitalini^1,*, Moira Madeo², Aldo Tava³

, Marcello Iriti¹

, Lisa Vallone⁴, Pinarosa Avato⁵, Clementina Elvezia Cocuzza², Paolo Simonetti⁶ and Maria Pia Argentieri⁵

¹ Dipartimento di Scienze Agrarie ed Ambientali, Università degli Studi di Milano, via G. Celoria 2, 20133 Milano, Italy

² Dipartimento di Medicina e Chirurgia, Università degli Studi di Milano-Bicocca, Via Cadore 48, 20900 Monza, MB, Italy

³ Consiglio per la Ricerca in Agricoltura e l’Analisi dell’Economia Agraria—Centro di Ricerca per le Produzioni Foraggere e Lattiero Casearie (CREA-FLC), viale Piacenza 29, 26900 Lodi, Italy

⁴ Dipartimento di Scienze Veterinarie per la Salute, la Produzione Animale e la Sicurezza Alimentare Università degli Studi di Milano, via Grasselli 7, 20137 Milano, Italy

⁵ Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari “Aldo Moro”, via Orabona 4, 70125 Bari, Italy

⁶ Dipartimento di Scienze per gli Alimenti, la Nutrizione e l’Ambiente, Università degli Studi di Milano, via G. Celoria 2, 20133 Milano, Italy

Molecules 2016, 21(7), 830; https://doi.org/10.3390/molecules21070830 - 25 Jun 2016

Cited by 34 | Viewed by 7116

Abstract

Aerial parts of Achillea moschata Wulfen (Asteraceae) growing wild in the Italian Rhaetian Alps were investigated to describe, for the first time, their phenolic content, as well as to characterize the essential oil. Inspection of the metabolic profile combining HPLC-DAD and ESI-MS/MS data [...] Read more.

Aerial parts of Achillea moschata Wulfen (Asteraceae) growing wild in the Italian Rhaetian Alps were investigated to describe, for the first time, their phenolic content, as well as to characterize the essential oil. Inspection of the metabolic profile combining HPLC-DAD and ESI-MS/MS data showed that the methanol extract contained glycosylated flavonoids with luteolin and apigenin as the main aglycones. Among them, the major compound was 7-O-glucosyl apigenin. Caffeoyl derivates were other phenolics identified. The essential oil obtained by steam distillation and investigated by GC/FID and GC/MS showed camphor, 1,8-cineole, and bornylacetate as the main constituents. The antioxidant capacity of three different extracts with increasing polarity and of the essential oil was evaluated by employing ABTS·+ and DPPH· radical scavenging assays. The methanolic extract was the only significantly effective sample against both synthetic radicals. All samples were also tested against Gram-positive (Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus) and Gram-negative (Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa) bacterial species using the disk diffusion assay. The non-polar extracts (dichloromethane and petroleum ether) and the essential oil possessed a broad spectrum of antimicrobial activity expressed according to inhibition zone diameter (8–24 mm). Full article

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

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12 pages, 2621 KiB

Open AccessArticle

A Metagenomic Advance for the Cloning and Characterization of a Cellulase from Red Rice Crop Residues

by Carlos Meneses^1,*

, Bruna Silva², Betsy Medeiros³, Rodrigo Serrato⁴

and David Johnston-Monje⁵

¹ Departament of Biology and Graduate Program in Agricultural Sciences, State University of Paraíba–UEPB, Campina Grande–PB 58429-500, Brazil

² Graduate Program in Agricultural Sciences, State University of Paraíba–UEPB, Campina Grande–PB 58429-500, Brazil

³ Departament of Biology, State University of Paraíba–UEPB, Campina Grande–PB 58429-500, Brazil

⁴ Department of Biochemistry and Molecular Biology, Federal University of Paraná–UFPR, Curitiba–PR 81.531-980, Brazil

⁵ Indigo Agriculture, Boston, MA 02129, USA

Molecules 2016, 21(7), 831; https://doi.org/10.3390/molecules21070831 - 25 Jun 2016

Cited by 27 | Viewed by 6437

Abstract

Many naturally-occurring cellulolytic microorganisms are not readily cultivable, demanding a culture-independent approach in order to study their cellulolytic genes. Metagenomics involves the isolation of DNA from environmental sources and can be used to identify enzymes with biotechnological potential from uncultured microbes. In this [...] Read more.

Many naturally-occurring cellulolytic microorganisms are not readily cultivable, demanding a culture-independent approach in order to study their cellulolytic genes. Metagenomics involves the isolation of DNA from environmental sources and can be used to identify enzymes with biotechnological potential from uncultured microbes. In this study, a gene encoding an endoglucanase was cloned from red rice crop residues using a metagenomic strategy. The amino acid identity between this gene and its closest published counterparts is lower than 70%. The endoglucanase was named EglaRR01 and was biochemically characterized. This recombinant protein showed activity on carboxymethylcellulose, indicating that EglaRR01 is an endoactive lytic enzyme. The enzymatic activity was optimal at a pH of 6.8 and at a temperature of 30 °C. Ethanol production from this recombinant enzyme was also analyzed on EglaRR01 crop residues, and resulted in conversion of cellulose from red rice into simple sugars which were further fermented by Saccharomyces cerevisiae to produce ethanol after seven days. Ethanol yield in this study was approximately 8 g/L. The gene found herein shows strong potential for use in ethanol production from cellulosic biomass (second generation ethanol). Full article

(This article belongs to the Section Molecular Diversity)

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13 pages, 2893 KiB

Open AccessArticle

Extraction Optimization of Polyphenols from Waste Kiwi Fruit Seeds (Actinidia chinensis Planch.) and Evaluation of Its Antioxidant and Anti-Inflammatory Properties

by Jianjun Deng¹, Qingqing Liu¹, Chao Zhang², Wei Cao¹, Daidi Fan^1,* and Haixia Yang^2,*

¹ Shaanxi Key Laboratory of Degradable Biomedical Materials, Department of Food Science and Engineering, College of Chemical Engineering, Northwest University, Xi’an 710069, China

² Department of Nutrition and Food Safety, School of Public Health, Xi’an Jiao Tong University, Xi’an 710061, China

Molecules 2016, 21(7), 832; https://doi.org/10.3390/molecules21070832 - 25 Jun 2016

Cited by 53 | Viewed by 11465

Abstract

Kiwi fruit (Actinidia chinensis Planch.) seeds, present as a by-product in the food and pharmaceutical industries, remain underutilized. In this study the extraction conditions for the maximum recovery of total phenolic content (TPC) with high DPPH scavenging capacities (DPPHsc) were analyzed for [...] Read more.

Kiwi fruit (Actinidia chinensis Planch.) seeds, present as a by-product in the food and pharmaceutical industries, remain underutilized. In this study the extraction conditions for the maximum recovery of total phenolic content (TPC) with high DPPH scavenging capacities (DPPHsc) were analyzed for kiwi fruit seed polyphenols (KSP) by response surface methodology. The optimal conditions for the highest yield of TPC (53.73 mg GAE/g DW) with 63.25% DPPHsc was found by using an extraction time of 79.65 min with an eluent containing 59.45% acetone at 38.35 °C and a 1:11.52 (w/v) solid/liquid ratio. Compared with butyl hydroxy toluene (BHT), a synthetic antioxidant, the extracted KSP showed higher DPPHsc and ferric reducing antioxidant power, but was less efficient than grape seed polyphenols extracted under the same optimum conditions. We also showed that the extracted KSP exhibited strong anti-inflammatory activities by suppressing the secretion of pro-inflammatory cytokines like interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α) in lipopolysaccharides (LPS)-induced RAW 264.7 cells. High performance liquid chromatography-electrochemical detector (HPLC-ECD) analysis of the extracted KSP under optimized conditions revealed that the extract was mainly composed of five polyphenolic compounds. Our work showed the development of an optimal extraction process of the KSP, which presented excellent antioxidant and anti-inflammatory activities, indicating that kiwi fruit seeds may further be utilized as a potential source of natural biological active compounds. Full article

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22 pages, 1989 KiB

Open AccessArticle

Analysis of Odorants in Marking Fluid of Siberian Tiger (Panthera tigris altaica) Using Simultaneous Sensory and Chemical Analysis with Headspace Solid-Phase Microextraction and Multidimensional Gas Chromatography-Mass Spectrometry-Olfactometry

by Simone B. Soso^1,2,† and Jacek A. Koziel^1,2,*,†

¹ Environmental Science Interdepartmental Graduate Program, Iowa State University, 1201 Sukup Hall, Ames, IA 50011, USA

² Department of Agricultural and Biosystems Engineering, Iowa State University, 4350 Elings Hall, Ames, IA 50011, USA

^† These authors contributed equally to this work.

Molecules 2016, 21(7), 834; https://doi.org/10.3390/molecules21070834 - 25 Jun 2016

Cited by 22 | Viewed by 9324

Abstract

Scent-marking is the most effective method of communication in the presence or absence of a signaler. These complex mixtures result in a multifaceted interaction triggered by the sense of smell. The objective was to identify volatile organic compound (VOC) composition and odors emitted [...] Read more.

Scent-marking is the most effective method of communication in the presence or absence of a signaler. These complex mixtures result in a multifaceted interaction triggered by the sense of smell. The objective was to identify volatile organic compound (VOC) composition and odors emitted by total marking fluid (MF) associated with Siberian tigers (Panthera tigris altaica). Siberian tiger, an endangered species, was chosen because its MF had never been analyzed. Solid phase microextraction (SPME) for headspace volatile collection combined with multidimensional gas chromatography-mass spectrometry-olfactometry for simultaneous chemical and sensory analyses were used. Thirty-two VOCs emitted from MF were identified. 2-acetyl-1-pyrroline, the sole previously identified compound responsible for the “characteristic” odor of P. tigris MF, was identified along with two additional compounds confirmed with standards (urea, furfural) and four tentatively identified compounds (3-methylbutanamine, (R)-3-methylcyclopentanone, propanedioic acid, and 3-hydroxybutanal) as being responsible for the characteristic aroma of Siberian tiger MF. Simultaneous chemical and sensory analyses improved characterization of scent-markings and identified compounds not previously reported in MF of other tiger species. This research will assist animal ecologists, behaviorists, and zookeepers in understanding how scents from specific MF compounds impact tiger and wildlife communication and improve management practices related to animal behavior. Simultaneous chemical and sensory analyses is applicable to unlocking scent-marking information for other species. Full article

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

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15 pages, 1156 KiB

Open AccessArticle

Chemical Synthesis of Deoxynivalenol-3-β-d-[¹³C₆]-glucoside and Application in Stable Isotope Dilution Assays

by Katharina Habler¹, Oliver Frank² and Michael Rychlik^1,*

¹ Analytical Food Chemistry, Technische Universität München, Alte Akademie 10, D-85354 Freising, Germany

² Food Chemistry and Molecular Sensory Science, Technische Universität München, Lise-Meitner-Straße 34, D-85354 Freising, Germany

Molecules 2016, 21(7), 838; https://doi.org/10.3390/molecules21070838 - 27 Jun 2016

Cited by 13 | Viewed by 6872

Abstract

Modified mycotoxins have been gaining importance in recent years and present a certain challenge in LC-MS/MS analysis. Due to the previous lack of a labeled isotopologue of the modified mycotoxin deoxynivalenol-3-glucoside, in our study we synthesized the first ¹³C-labeled internal standard. Therefore, [...] Read more.

Modified mycotoxins have been gaining importance in recent years and present a certain challenge in LC-MS/MS analysis. Due to the previous lack of a labeled isotopologue of the modified mycotoxin deoxynivalenol-3-glucoside, in our study we synthesized the first ¹³C-labeled internal standard. Therefore, we used the Königs-Knorr method to synthesize deoxynivalenol-3-β-d-[¹³C₆]-glucoside originated from unlabeled deoxynivalenol and [¹³C₆]-labeled glucose. Using the synthesized isotopically-labeled standard deoxynivalenol-3-β-d-[¹³C₆]-glucoside and the purchased labeled standard [¹³C₁₅]-deoxynivalenol, a stable isotope dilution LC-MS/MS method was firstly developed for deoxynivalenol-3-glucoside and deoxynivalenol in beer. The preparation and purification of beer samples was based on a solid phase extraction. The validation data of the newly developed method gave satisfying results. Intra- and interday precision studies revealed relative standard deviations below 0.5% and 7%, respectively. The recoveries ranged for both analytes between 97% and 112%. The stable isotope dilution assay was applied to various beer samples from four different countries. In summary, deoxynivalenol-3-glucoside and deoxynivalenol mostly appeared together in varying molar ratios but were quantified in rather low contents in the investigated beers. Full article

(This article belongs to the Special Issue Natural Toxins)

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17 pages, 2499 KiB

Open AccessArticle

Artonin E and Structural Analogs from Artocarpus Species Abrogates Estrogen Receptor Signaling in Breast Cancer

by Imaobong Etti^1,2,*

, Rasedee Abdullah^3,*, Najihah Mohd Hashim⁴, Arifah Kadir⁵, Ahmad Bustamam Abdul⁶, Christopher Etti⁷, Ibrahim Malami⁶

, Peter Waziri⁶ and Chee Wun How⁸

¹ Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang 43400, Malaysia

² Department of Pharmacology and Toxicology, University of Uyo, Uyo 520271, Nigeria

³ Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, University Putra Malaysia, Serdang 43400, Malaysia

⁴ Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia

⁵ Department of Veterinary Preclinical Science, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang 43400, Malaysia

⁶ MAKNA-Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Malaysia

⁷ Department of Agricultural and Food Engineering, University of Uyo, Uyo 520271, Nigeria

⁸ Laboratory of Vaccine and Immunotherapeutics, Institute of Bioscience, University Putra Malaysia, Serdang 43400, Malaysia

Molecules 2016, 21(7), 839; https://doi.org/10.3390/molecules21070839 - 29 Jun 2016

Cited by 26 | Viewed by 6286

Abstract

The increasing rate of mortality ensued from breast cancer has encouraged research into safer and efficient therapy. The human Estrogen receptor α has been implicated in the majority of reported breast cancer cases. Molecular docking employing Glide, Schrodinger suite 2015, was used to [...] Read more.

The increasing rate of mortality ensued from breast cancer has encouraged research into safer and efficient therapy. The human Estrogen receptor α has been implicated in the majority of reported breast cancer cases. Molecular docking employing Glide, Schrodinger suite 2015, was used to study the binding affinities of small molecules from the Artocarpus species after their drug-like properties were ascertained. The structure of the ligand-binding domain of human Estrogen receptor α was retrieved from Protein Data Bank while the structures of compounds were collected from PubChem database. The binding interactions of the studied compounds were reported as well as their glide scores. The best glide scored ligand, was Artonin E with a score of −12.72 Kcal when compared to other studied phytomolecules and it evoked growth inhibition of an estrogen receptor positive breast cancer cells in submicromolar concentration (3.8–6.9 µM) in comparison to a reference standard Tamoxifen (18.9–24.1 µM) within the tested time point (24–72 h). The studied ligands, which had good interactions with the target receptor, were also drug-like when compared with 95% of orally available drugs with the exception of Artoelastin, whose predicted physicochemical properties rendered it less drug-like. The in silico physicochemical properties, docking interactions and growth inhibition of the best glide scorer are indications of the anti-breast cancer relevance of the studied molecules. Full article

(This article belongs to the Section Natural Products Chemistry)

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11 pages, 1277 KiB

Open AccessArticle

Integrated Analysis of the Wood Oil from Xanthocyparis vietnamensis Farjon & Hiep. by Chromatographic and Spectroscopic Techniques

by Ophélie Bazzali¹, Tran Huy Thai², Tran Minh Hoi², Nguyen Sinh Khang², Nguyen Thi Hien², Joseph Casanova¹, Ange Bighelli¹ and Félix Tomi^1,*

¹ Université de Corse-CNRS, UMR 6134 SPE, Equipe Chimie et Biomasse, Route des Sanguinaires, 20000 Ajaccio, France

² Institute of Ecology and Biological Resources, Vietnam Academy of Science and Technology, Cau Giay, Hanoi 10000, Vietnam

Molecules 2016, 21(7), 840; https://doi.org/10.3390/molecules21070840 - 27 Jun 2016

Cited by 22 | Viewed by 6443

Abstract

In order to get better knowledge about the volatiles produced by Xanthocyparis vietnamensis, a species recently discovered in Vietnam, its wood oil has been analyzed by a combination of chromatographic (GC, CC) and spectroscopic (GC-MS, ¹³C-NMR) techniques. Forty components that accounted for [...] Read more.

In order to get better knowledge about the volatiles produced by Xanthocyparis vietnamensis, a species recently discovered in Vietnam, its wood oil has been analyzed by a combination of chromatographic (GC, CC) and spectroscopic (GC-MS, ¹³C-NMR) techniques. Forty components that accounted for 87.9% of the oil composition have been identified. The composition is dominated by nootkatene (20.7%), 11,12,13-tri-nor-eremophil-1(10)-en-7-one (17.2%), γ-eudesmol (5.1%), nootkatone (4.7%), valencene (3.5%) and 13-nor-eremophil-1(10)-en-11-one (2.6%). The structure of two new compounds—10-epi-nor-γ-eudesmen-11-one and 12-hydroxy-isodihydroagarofuran—has been elucidated, while 11,12,13-tri-nor-eremophil-1(10)-en-7-ol is reported as a natural product for the first time. The composition of X. vietnamensis wood oil varied drastically from those of leaf oils, dominated by hedycaryol (34.4%), phyllocladene (37.8%) or by pimara-6(14)-15-diene (19.4%). Full article

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

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16 pages, 5203 KiB

Open AccessArticle

Synthesis and Evaluation of Ciprofloxacin-Nitroxide Conjugates as Anti-Biofilm Agents

by Anthony D. Verderosa¹, Sarah C. Mansour², César De la Fuente-Núñez^3,4,5,6, Robert E. W. Hancock² and Kathryn E. Fairfull-Smith^1,*

¹ ARC Centre of Excellence for Free Radical Chemistry and Biotechnology, Faculty of Science and Engineering, Queensland University of Technology, Queensland 4001, Australia

² Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada

³ Synthetic Biology Group, MIT Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

⁴ Research Laboratory of Electronics, Department of Biological Engineering, Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge 02139, MA, USA

⁵ Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA

⁶ Harvard Biophysics Program, Harvard University, Boston, MA 02115, USA

Molecules 2016, 21(7), 841; https://doi.org/10.3390/molecules21070841 - 27 Jun 2016

Cited by 32 | Viewed by 9476

Abstract

As bacterial biofilms are often refractory to conventional antimicrobials, the need for alternative and/or novel strategies for the treatment of biofilm related infections has become of paramount importance. Herein, we report the synthesis of novel hybrid molecules comprised of two different hindered nitroxides [...] Read more.

As bacterial biofilms are often refractory to conventional antimicrobials, the need for alternative and/or novel strategies for the treatment of biofilm related infections has become of paramount importance. Herein, we report the synthesis of novel hybrid molecules comprised of two different hindered nitroxides linked to the piperazinyl secondary amine of ciprofloxacin via a tertiary amine linker achieved utilising reductive amination. The corresponding methoxyamine derivatives were prepared alongside their radical-containing counterparts as controls. Subsequent biological evaluation of the hybrid compounds on preformed P. aeruginosa flow cell biofilms divulged significant dispersal and eradication abilities for ciprofloxacin-nitroxide hybrid compound 10 (up to 95% eradication of mature biofilms at 40 μM). Importantly, these hybrids represent the first dual-action antimicrobial-nitroxide agents, which harness the dispersal properties of the nitroxide moiety to circumvent the well-known resistance of biofilms to treatment with antimicrobial agents. Full article

(This article belongs to the Special Issue Free Radicals in Organic Synthesis)

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12 pages, 1017 KiB

Open AccessCommunication

A One-Pot Tandem Strategy in Catalytic Asymmetric Vinylogous Aldol Reaction of Homoallylic Alcohols

by Xufeng Hou¹, Zhenzhong Jing², Xiangbin Bai² and Zhiyong Jiang^1,2,*

¹ School of Chemistry and Chemical Engineering, Xuchang University, Xuchang 461000, China

² Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University, Jinming Campus, Kaifeng 475004, Henan, China

Molecules 2016, 21(7), 842; https://doi.org/10.3390/molecules21070842 - 27 Jun 2016

Cited by 6 | Viewed by 5838

Abstract

Reported is a rationally-designed one-pot sequential strategy that allows homoallylic alcohols to be employed in a catalytic, asymmetric, direct vinylogous aldol reaction with a series of activated acyclic ketones, including trifluoromethyl ketones, γ-ketoesters, and α-keto phosphonates, in high yields (up to 95%) with [...] Read more.

Reported is a rationally-designed one-pot sequential strategy that allows homoallylic alcohols to be employed in a catalytic, asymmetric, direct vinylogous aldol reaction with a series of activated acyclic ketones, including trifluoromethyl ketones, γ-ketoesters, and α-keto phosphonates, in high yields (up to 95%) with excellent regio- and enantio-selectivity (up to 99% ee). This modular combination, including Jones oxidation and asymmetric organocatalysis, has satisfactory compatibility and reliability even at a 20 mmol scale, albeit without intermediary purification. Full article

(This article belongs to the Special Issue Cascade Catalysis)

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16 pages, 8681 KiB

Open AccessArticle

Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells—Characterization of a New in Vivo Model

by Sonja Stojković¹, Ana Podolski-Renić¹, Jelena Dinić¹

, Željko Pavković¹, Jose M. Ayuso^2,3,4, Luis J. Fernández^2,3,4

, Ignacio Ochoa^2,3,4

, Victor M. Pérez-García⁵

, Vesna Pešić¹ and Milica Pešić^1,*

¹ Department of Neurobiology, Institute for Biological Research “Siniša Stanković”, University of Belgrade, Despota Stefana 142, Belgrade 11060, Serbia

² Group of Structural Mechanics and Materials Modeling (GEMM), Centro Investigacion Biomedica en Red. Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Aragon 50018, Spain

³ Aragón Institute of Engineering Research (I3A), University of Zaragoza, Zaragoza, Aragon 50018, Spain

⁴ Aragon Institute of Biomedical Research, Instituto de Salud Carlos III, Madrid, Madrid 28029, Spain

⁵ Departamento de Matemáticas, E.T.S.I. Industriales and Instituto de Matemática Aplicada a la Ciencia y la Ingeniería (IMACI), Universidad de Castilla-La Mancha, Ciudad Real 13071, Spain

Molecules 2016, 21(7), 843; https://doi.org/10.3390/molecules21070843 - 27 Jun 2016

Cited by 10 | Viewed by 6897

Abstract

Chemoresistance and invasion properties are severe limitations to efficient glioma therapy. Therefore, development of glioma in vivo models that more accurately resemble the situation observed in patients emerges. Previously, we established RC6 rat glioma cell line resistant to DNA damaging agents including antiglioma [...] Read more.

Chemoresistance and invasion properties are severe limitations to efficient glioma therapy. Therefore, development of glioma in vivo models that more accurately resemble the situation observed in patients emerges. Previously, we established RC6 rat glioma cell line resistant to DNA damaging agents including antiglioma approved therapies such as 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and temozolomide (TMZ). Herein, we evaluated the invasiveness of RC6 cells in vitro and in a new orthotopic animal model. For comparison, we used C6 cells from which RC6 cells originated. Differences in cell growth properties were assessed by real-time cell analyzer. Cells’ invasive potential in vitro was studied in fluorescently labeled gelatin and by formation of multicellular spheroids in hydrogel. For animal studies, fluorescently labeled cells were inoculated into adult male Wistar rat brains. Consecutive coronal and sagittal brain sections were analyzed 10 and 25 days post-inoculation, while rats’ behavior was recorded during three days in the open field test starting from 25th day post-inoculation. We demonstrated that development of chemoresistance induced invasive phenotype of RC6 cells with significant behavioral impediments implying usefulness of orthotopic RC6 glioma allograft in preclinical studies for the examination of new approaches to counteract both chemoresistance and invasion of glioma cells. Full article

(This article belongs to the Special Issue New Approaches to Counteract Drug Resistance in Cancer)

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15 pages, 4610 KiB

Open AccessArticle

Relevance of the Pharmacokinetic and Pharmacodynamic Profiles of Puerariae lobatae Radix to Aggregation of Multi-Component Molecules in Aqueous Decoctions

by Bili Su^1,2,†, Yongjun Kan^1,†, Jianwei Xie², Juan Hu^1,2,*

and Wensheng Pang^2,*

¹ The Institute of Drug Research, Fujian Academy of Traditional Chinese Medicine, Fuzhou 350003, China

² The College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China

^† These authors contributed equally to this work.

Molecules 2016, 21(7), 845; https://doi.org/10.3390/molecules21070845 - 28 Jun 2016

Cited by 16 | Viewed by 5589

Abstract

The complexity of traditional Chinese medicines (TCMs) is related to their multi-component system. TCM aqueous decoction is a common clinical oral formulation. Between molecules in solution, there exist intermolecular strong interactions to form chemical bonds or weak non-bonding interactions such as hydrogen bonds [...] Read more.

The complexity of traditional Chinese medicines (TCMs) is related to their multi-component system. TCM aqueous decoction is a common clinical oral formulation. Between molecules in solution, there exist intermolecular strong interactions to form chemical bonds or weak non-bonding interactions such as hydrogen bonds and Van der Waals forces, which hold molecules together to form “molecular aggregates”. Taking the TCM Puerariae lobatae Radix (Gegen) as an example, we explored four Gegen decoctions of different concentration of 0.019, 0.038, 0.075, and 0.30 g/mL, named G-1, G-2, G-3, and G-4. In order of molecular aggregate size (diameter) the four kinds of solution were ranked G-1 < G-2 < G-3 < G-4 by Flow Cell 200S IPAC image analysis. A rabbit vertebrobasilar artery insufficiency (VBI) model was set up and they were given Gegen decoction (GGD) at a clinical dosage of 0.82 g/kg (achieved by adjusting the gastric perfusion volume depending on the concentration). The HPLC fingerprint of rabbit plasma showed that the chemical component absorption into blood in order of peak area values was G-1 < G-2 > G-3 > G-4. Puerarin and daidzin are the major constituents of Gegen, and the pharmacokinetics of G-1 and G-2 puerarin conformed with the two compartment open model, while for G-3 and G-4, they conformed to a one compartment open model. For all four GGDs the pharmacokinetics of daidzin complied with a one compartment open model. FQ-PCR assays of rabbits’ vertebrobasilar arterial tissue were performed to determine the pharmacodynamic profiles of the four GGDs. GGD markedly lowered the level of AT₁R mRNA, while the AT₂R mRNA level was increased significantly vs. the VBI model, and G-2 was the most effective. In theory the dosage was equal to the blood drug concentration and should be consistent; however, the formation of molecular aggregates affects drug absorption and metabolism, and therefore influences drugs’ effects. Our data provided references for the rational use of Chinese medicines in the clinic, such as the best oral preparation and decoction concentration. Full article

(This article belongs to the Section Medicinal Chemistry)

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23 pages, 9188 KiB

Open AccessArticle

An NMR-Guided Screening Method for Selective Fragment Docking and Synthesis of a Warhead Inhibitor

by Ram B. Khattri^1,†

, Daniel L. Morris^1,†, Caroline M. Davis¹, Stephanie M. Bilinovich², Andrew J. Caras¹, Matthew J. Panzner¹, Michael A. Debord¹ and Thomas C. Leeper^1,*

¹ Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA

² Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA

^† These authors contributed equally to this work.

Molecules 2016, 21(7), 846; https://doi.org/10.3390/molecules21070846 - 16 Jul 2016

Cited by 7 | Viewed by 8848

Abstract

Selective hits for the glutaredoxin ortholog of Brucella melitensis are determined using STD NMR and verified by trNOE and ¹⁵N-HSQC titration. The most promising hit, RK207, was docked into the target molecule using a scoring function to compare simulated poses to experimental [...] Read more.

Selective hits for the glutaredoxin ortholog of Brucella melitensis are determined using STD NMR and verified by trNOE and ¹⁵N-HSQC titration. The most promising hit, RK207, was docked into the target molecule using a scoring function to compare simulated poses to experimental data. After elucidating possible poses, the hit was further optimized into the lead compound by extension with an electrophilic acrylamide warhead. We believe that focusing on selectivity in this early stage of drug discovery will limit cross-reactivity that might occur with the human ortholog as the lead compound is optimized. Kinetics studies revealed that lead compound 5 modified with an ester group results in higher reactivity than an acrylamide control; however, after modification this compound shows little selectivity for bacterial protein versus the human ortholog. In contrast, hydrolysis of compound 5 to the acid form results in a decrease in the activity of the compound. Together these results suggest that more optimization is warranted for this simple chemical scaffold, and opens the door for discovery of drugs targeted against glutaredoxin proteins—a heretofore untapped reservoir for antibiotic agents. Full article

(This article belongs to the Special Issue Developments in Fragment-Based Lead Discovery)

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18 pages, 1686 KiB

Open AccessArticle

Rational Design and Synthesis of New, High Efficiency, Multipotent Schiff Base-1,2,4-triazole Antioxidants Bearing Butylated Hydroxytoluene Moieties

by Wageeh A Yehye^1,*

, Noorsaadah Abdul Rahman^2,3, Omar Saad⁴, Azhar Ariffin², Sharifah Bee Abd Hamid¹, Abeer A. Alhadi^2,3, Farkaad A. Kadir⁵, Marzieh Yaeghoobi^2,3 and Abdulsalam A. Matlob⁶

¹ Nanotechnology & Catalysis Research Centre (NANOCAT), University of Malaya, Block 3A, Institute of Postgraduate Studies Building, Kuala Lumpur 50603, Malaysia

² Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia

³ Drug Design and Development Research Group, Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia

⁴ Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia

⁵ Division of Human Biology, School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia

⁶ Department of Environmental Technology, College of Environment, Mosul University, Mosul 41001, Iraq

Molecules 2016, 21(7), 847; https://doi.org/10.3390/molecules21070847 - 28 Jun 2016

Cited by 34 | Viewed by 10452

Abstract

A new series of multipotent antioxidants (MPAOs), namely Schiff base-1,2,4-triazoles attached to the oxygen-derived free radical scavenging moiety butylated hydroxytoluene (BHT) were designed and subsequently synthesized. The structure-activity relationship (SAR) of the designed antioxidants was established alongside the prediction of activity spectra for [...] Read more.

A new series of multipotent antioxidants (MPAOs), namely Schiff base-1,2,4-triazoles attached to the oxygen-derived free radical scavenging moiety butylated hydroxytoluene (BHT) were designed and subsequently synthesized. The structure-activity relationship (SAR) of the designed antioxidants was established alongside the prediction of activity spectra for substances (PASS). The antioxidant activities of the synthesized compounds 4–10 were tested by the DPPH bioassay. The synthesized compounds 4–10 inhibited stable DPPH free radicals at a level that is 10⁻⁴ M more than the well-known standard antioxidant BHT. Compounds 8–10 with para-substituents were less active than compounds 4 and 5 with trimethoxy substituents compared to those with a second BHT moiety (compounds 6 and 7). With an IC₅₀ of 46.13 ± 0.31 µM, compound 6 exhibited the most promising in vitro inhibition at 89%. Therefore, novel MPAOs containing active triazole rings, thioethers, Schiff bases, and BHT moieties are suggested as potential antioxidants for inhibiting oxidative stress processes and scavenging free radicals, hence, this combination of functions is anticipated to play a vital role in repairing cellular damage, preventing various human diseases and in medical therapeutic applications. Full article

(This article belongs to the Special Issue Free Radicals in Organic Synthesis)

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14 pages, 4434 KiB

Open AccessArticle

Ultrasonic Synthesis, Molecular Structure and Mechanistic Study of 1,3-Dipolar Cycloaddition Reaction of 1-Alkynylpyridinium-3-olate and Acetylene Derivatives

by Asmaa Aboelnaga^1,2, Mohamed Hagar^1,4,*

and Saied M. Soliman^3,4

¹ Department of Chemistry, Faculty of Science, Taibah University, Yanbu branch, Yanbu 00000, Saudi Arabia

² Department of Chemistry, Faculty of Women for Arts, Science and Education, Ain Shams University, Heliopolis, Cairo 11757, Egypt

³ Department of Chemistry, College of Science & Arts, King Abdulaziz University, P.O. Box 344, Rabigh 21911, Saudi Arabia

⁴ Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 21321, Egypt

Molecules 2016, 21(7), 848; https://doi.org/10.3390/molecules21070848 - 29 Jun 2016

Cited by 30 | Viewed by 5970

Abstract

Regioselectively, ethyl propiolate reacted with 1-(propergyl)-pyridinium-3-olate to give two regioisomers; ethyl 4-oxo-8-(prop-2-ynyl)-8-aza-bicyclo(3.2.1)octa-2,6-diene-6-carboxylate 4, ethyl 2-oxo-8-(prop-2-ynyl)-8-aza-bicyclo(3.2.1)octa-3,6-diene-6-carboxylate 5 as well as ethyl 2,6-dihydro-6-(prop-2-ynyl)furo(2,3-c)pyridine-3-carboxylate 6. The obtained compounds were identified by their spectral (IR, mass and NMR) data. Moreover, DFT quantum chemical calculations were [...] Read more.

Regioselectively, ethyl propiolate reacted with 1-(propergyl)-pyridinium-3-olate to give two regioisomers; ethyl 4-oxo-8-(prop-2-ynyl)-8-aza-bicyclo(3.2.1)octa-2,6-diene-6-carboxylate 4, ethyl 2-oxo-8-(prop-2-ynyl)-8-aza-bicyclo(3.2.1)octa-3,6-diene-6-carboxylate 5 as well as ethyl 2,6-dihydro-6-(prop-2-ynyl)furo(2,3-c)pyridine-3-carboxylate 6. The obtained compounds were identified by their spectral (IR, mass and NMR) data. Moreover, DFT quantum chemical calculations were used to study the mechanism of the cycloaddition reaction. The regioselectivity was explained using transition state calculations, where the calculations agreed with the formation of products 4 and 5 in almost the same ratio. The reaction was also extended for diphenylaceylene as dipolarophile to give only two products instead of three. Full article

(This article belongs to the Special Issue Pericyclic Reactions)

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14 pages, 6394 KiB

Open AccessArticle

Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX) and Sirtuin1 (SIRT1)

by Ming-Hung Lin^1,2, Yi-Hui Lee¹, Hsiao-Ling Cheng¹, Huei-Yu Chen¹, Fong-Han Jhuang¹ and Pin Ju Chueh^1,3,4,5,*

¹ Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan

² Tainan Municipal An-Nan Hospital, China Medical University, Tainan 70965, Taiwan

³ Graduate Institute of Basic Medicine, China Medical University, Taichung 40402, Taiwan

⁴ Department of Medical Research, China Medical University Hospital, Taichung 40402, Taiwan

⁵ Department of Biotechnology, Asia University, Taichung 41354, Taiwan

Molecules 2016, 21(7), 849; https://doi.org/10.3390/molecules21070849 - 28 Jun 2016

Cited by 51 | Viewed by 8124

Abstract

Bladder cancer is one of the most frequent cancers among males, and its poor survival rate reflects problems with aggressiveness and chemo-resistance. Recent interest has focused on the use of chemopreventatives (nontoxic natural agents that may suppress cancer progression) to induce targeted apoptosis [...] Read more.

Bladder cancer is one of the most frequent cancers among males, and its poor survival rate reflects problems with aggressiveness and chemo-resistance. Recent interest has focused on the use of chemopreventatives (nontoxic natural agents that may suppress cancer progression) to induce targeted apoptosis for cancer therapy. Capsaicin, which has anti-cancer properties, is one such agent. It is known to preferentially inhibit a tumor-associated NADH oxidase (tNOX) that is preferentially expressed in cancer/transformed cells. Here, we set out to elucidate the correlation between tNOX expression and the inhibitory effects of capsaicin in human bladder cancer cells. We showed that capsaicin downregulates tNOX expression and decreases bladder cancer cell growth by enhancing apoptosis. Moreover, capsaicin was found to reduce the expression levels of several proteins involved in cell cycle progression, in association with increases in the cell doubling time and enhanced cell cycle arrest. Capsaicin was also shown to inhibit the activation of ERK, thereby reducing the phosphorylation of paxillin and FAK, which leads to decreased cell migration. Finally, our results indicate that RNA interference-mediated tNOX depletion enhances spontaneous apoptosis, prolongs cell cycle progression, and reduces cell migration and the epithelial-mesenchymal transition. We also observed a downregulation of sirtuin 1 (SIRT1) in these tNOX-knockdown cells, a deacetylase that is important in multiple cellular functions. Taken together, our results indicate that capsaicin inhibits the growth of bladder cancer cells by inhibiting tNOX and SIRT1 and thereby reducing proliferation, attenuating migration, and prolonging cell cycle progression. Full article

(This article belongs to the Special Issue Capsaicin)

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13 pages, 1420 KiB

Open AccessArticle

Quality Evaluation of Scrophulariae Radix Processed by Different ‘Sweating’ Methods Based on Simultaneous Determination of Multiple Bioactive Constituents Combined with Grey Relational Analysis

by Shengnan Wang¹, Yujiao Hua¹, Li Xu², Lisi Zou¹, Xunhong Liu^1,*, Yiyuan Luo¹, Juanxiu Liu¹ and Ying Yan¹

¹ College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China

² Yangzhou Institute for Drug Control, Yangzhou 225100, China

Molecules 2016, 21(7), 850; https://doi.org/10.3390/molecules21070850 - 28 Jun 2016

Cited by 27 | Viewed by 5366

Abstract

Scrophulariae Radix is one of the most popular traditional Chinese medicines (TCMs), which needs to be processed by ‘sweating’ methods. Primary processing of Scrophulariae Radix is an important link which closely relates to the quality of products in this TCM. To facilitate selection [...] Read more.

Scrophulariae Radix is one of the most popular traditional Chinese medicines (TCMs), which needs to be processed by ‘sweating’ methods. Primary processing of Scrophulariae Radix is an important link which closely relates to the quality of products in this TCM. To facilitate selection of the suitable ‘sweating’ processing method for Scrophulariae Radix, in this study the quality of Scrophulariae Radix processed by different ‘sweating’ methods was evaluated based on simultaneous determination of multiple bioactive constituents combined with grey relational analysis. The contents of iridoid glycosides, phenylpropanoid glycosides, and organic acids in Scrophulariae Radix processed by different ‘sweating’ methods were simultaneously determined using ultra high performance liquid chromatography coupled with triple quadrupole-linear ion trap mass spectrometry (UPLC-QTRAP-MS/MS). Furthermore, grey relational analysis (GRA) was performed to evaluate the ‘sweating’ processed samples according to the contents of twelve constituents. All of the results demonstrated that the quality of Scrophulariae Radix processed by oven drying at 35 °C and ‘sweating’ for three days was better. The developed method was useful for the overall assessment on quality of Scrophulariae Radix, and this study may provide the foundation and support for ‘sweating’ processing of Scrophulariae Radix in normalization and standardization. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 5530 KiB

Open AccessArticle

The Effects and Mechanisms of Periplaneta americana Extract Reversal of Multi-Drug Resistance in BEL-7402/5-FU Cells

by Falu Yuan^1,†

, Junyong Liu^1,†, Tingting Qiao¹, Ting Li¹, Qi Shen²

and Fang Peng^1,3,*

¹ College of Pharmacy and Chemistry, Dali University, Dali 671000, Yunnan, China

² College of Pharmacy, Shanghai Jiaotong University, Shanghai 200240, China

³ Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R & D, Dali University, Dali 671000, Yunnan, China

^† These authors contributed equally to this study.

Molecules 2016, 21(7), 852; https://doi.org/10.3390/molecules21070852 - 28 Jun 2016

Cited by 14 | Viewed by 6735

Abstract

The present study reports the reversing effects of extracts from P. americana on multidrug resistance of BEL-7402/5-FU cells, as well as a preliminary investigation on their mechanism of action. A methylthiazolyl tetrazolium (MTT) method was applied to determine the multidrug resistance of BEL-7402/5-FU, [...] Read more.

The present study reports the reversing effects of extracts from P. americana on multidrug resistance of BEL-7402/5-FU cells, as well as a preliminary investigation on their mechanism of action. A methylthiazolyl tetrazolium (MTT) method was applied to determine the multidrug resistance of BEL-7402/5-FU, while an intracellular drug accumulation assay was used to evaluate the effects of a column chromatography extract (PACC) and defatted extract (PADF) from P. americana on reversing multi-drug resistance. BEL-7402/5-FU reflected high resistance to 5-FU; PACC and PADF could promote drug accumulation in BEL-7402/5-FU cells, among which PADF was more effective than PACC. Moreover, results from the immunocytochemical method showed that PACC and PADF could downregulate the expression of drug resistance-associated proteins (P-gp, MRP, LRP); PACC and PADF had no effects on the expression of multidrug resistance-associated enzymes (GST-π), but PACC could increase the expression of multidrug resistance-associated enzymes (PKC). Results of real-time fluorescence quantitative PCR revealed that PACC and PADF were able to markedly inhibit the expression of multidrug resistance-associated genes (MDR1, LRP and MRP1); PACC presented a significant impact on the gene expression of multidrug resistance-associated enzymes, which increased the gene expression of GST-π and PKC. However, PADF had little impact on the expression of multidrug resistance-associated enzymes. These results demonstrated that PACC and PADF extracted from P. americana could effectively reverse MDR in BEL-7402/5-FU cells, whose mechanism was to inhibit the expression of P-gp, MRP, and LRP, and that PADF was more effective in the reversal of MDR than did PACC. In addition, some of extracts from P. americana altered (sometimes increasing) the expression of multidrug resistance-associated enzymes. Full article

(This article belongs to the Special Issue New Approaches to Counteract Drug Resistance in Cancer)

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18 pages, 1332 KiB

Open AccessArticle

In Silico Mining for Antimalarial Structure-Activity Knowledge and Discovery of Novel Antimalarial Curcuminoids

by Birgit Viira^1,2,3, Thibault Gendron², Don Antoine Lanfranchi², Sandrine Cojean⁴, Dragos Horvath^3,*

, Gilles Marcou³, Alexandre Varnek³, Louis Maes⁵, Uko Maran¹, Philippe M. Loiseau⁴ and Elisabeth Davioud-Charvet^2,*

¹ Institute of Chemistry, University of Tartu, 50411 Tartu, Estonia

² Bioorganic and Medicinal Chemistry Team, UMR 7509 CNRS-Université de Strasbourg, European School of Chemistry, Polymers and Materials (ECPM), 25, rue Becquerel, Strasbourg F-67087, France

³ Laboratoire de Chemoinformatique, UMR7140 CNRS-Université de Strasbourg, 1 rue Blaise Pascal, Strasbourg F-67000, France

⁴ Antiparasitic Chemotherapy, Faculty of Pharmacy, BioCIS, UMR 8076 CNRS-Université Paris-Sud, Rue Jean-Baptiste Clément, Chatenay-Malabry F-92290, France

⁵ Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1, Antwerp B-2610, Belgium

Molecules 2016, 21(7), 853; https://doi.org/10.3390/molecules21070853 - 29 Jun 2016

Cited by 21 | Viewed by 8844

Abstract

Malaria is a parasitic tropical disease that kills around 600,000 patients every year. The emergence of resistant Plasmodium falciparum parasites to artemisinin-based combination therapies (ACTs) represents a significant public health threat, indicating the urgent need for new effective compounds to reverse ACT resistance [...] Read more.

Malaria is a parasitic tropical disease that kills around 600,000 patients every year. The emergence of resistant Plasmodium falciparum parasites to artemisinin-based combination therapies (ACTs) represents a significant public health threat, indicating the urgent need for new effective compounds to reverse ACT resistance and cure the disease. For this, extensive curation and homogenization of experimental anti-Plasmodium screening data from both in-house and ChEMBL sources were conducted. As a result, a coherent strategy was established that allowed compiling coherent training sets that associate compound structures to the respective antimalarial activity measurements. Seventeen of these training sets led to the successful generation of classification models discriminating whether a compound has a significant probability to be active under the specific conditions of the antimalarial test associated with each set. These models were used in consensus prediction of the most likely active from a series of curcuminoids available in-house. Positive predictions together with a few predicted as inactive were then submitted to experimental in vitro antimalarial testing. A large majority from predicted compounds showed antimalarial activity, but not those predicted as inactive, thus experimentally validating the in silico screening approach. The herein proposed consensus machine learning approach showed its potential to reduce the cost and duration of antimalarial drug discovery. Full article

(This article belongs to the Special Issue COST CM1307: Targeted Chemotherapy towards Diseases Caused by Endoparasites—Proceedings in Medicinal and Natural Product Chemistry)

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7 pages, 713 KiB

Open AccessArticle

Dyeing of Polyester with Disperse Dyes: Part 2. Synthesis and Dyeing Characteristics of Some Azo Disperse Dyes for Polyester Fabrics

by Alya M. Al-Etaibi^1,*, Huda S. Alnassar² and Morsy Ahmed El-Apasery³

¹ Natural Science Department, College of Health Science, Public Authority for Applied Education and Training, Fayha 72853, Kuwait

² Department of Laboratories Technology, College of Technological Studies, Public Authority for Applied Education and Training, Fayha 70654, Kuwait

³ Dyeing, Printing and Textile Auxiliaries Department, Textile Research Division, National Research Centre, 33 El Buhouth St., Dokki, Cairo 12311, Egypt

Molecules 2016, 21(7), 855; https://doi.org/10.3390/molecules21070855 - 29 Jun 2016

Cited by 48 | Viewed by 9888

Abstract

The goal of this study was to utilize carrier for accelerating the rate of dyeing not only to enhance dyeing of polyester fabrics dyed with disperse dyes 3a,b, but also to save energy. Both the color strength expressed as dye [...] Read more.

The goal of this study was to utilize carrier for accelerating the rate of dyeing not only to enhance dyeing of polyester fabrics dyed with disperse dyes 3a,b, but also to save energy. Both the color strength expressed as dye uptake and the fastness properties of the dyed fabrics were evaluated. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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9 pages, 1929 KiB

Open AccessArticle

Study of the Activity and Possible Mechanism of Action of a Reversible Inhibitor of Recombinant Human KAT-2: A Promising Lead in Neurodegenerative and Cognitive Disorders

by Alireza Nematollahi^1,*, Guanchen Sun¹, Gayan S. Jayawickrama¹, Jane R. Hanrahan² and W. Bret Church^1,*

¹ Group in Biomolecular Structure and Informatics, Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia

² Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia

Molecules 2016, 21(7), 856; https://doi.org/10.3390/molecules21070856 - 29 Jun 2016

Cited by 18 | Viewed by 6606

Abstract

Abnormal levels of kynurenic acid (KYNA) in the human brain are believed to be connected to several central nervous system (CNS) diseases, therefore compounds which affect the production of this crucial metabolite are of interest in CNS drug development. The majority of KYNA [...] Read more.

Abnormal levels of kynurenic acid (KYNA) in the human brain are believed to be connected to several central nervous system (CNS) diseases, therefore compounds which affect the production of this crucial metabolite are of interest in CNS drug development. The majority of KYNA production is accounted for by kynurenine aminotransferase-2 (KAT-2) in the mammalian brain; hence this enzyme is one of the most interesting targets with which to modulate KYNA levels. Recently developed human KAT-2 inhibitors with high potencies are known to irreversibly bind to the enzyme cofactor, pyridoxal-5′-phosphate (PLP), which may lead to severe side effects due to the abundance of PLP-dependent enzymes. In this study, we report a reversible and competitive inhibitor of KAT-2. Its inhibitory activities were examined using HPLC and surface plasmon resonance (SPR) and compare favorably with other recently reported KAT-2 inhibitors. Our inhibitor, NS-1502, demonstrates suitable inhibitory activity, almost 10 times more potent than the known reversible KAT-2, (S)-ESBA. Full article

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12 pages, 1611 KiB

Open AccessArticle

Molecular Dynamics Simulations to Investigate the Binding Mode of the Natural Product Liphagal with Phosphoinositide 3-Kinase α

by Yanjuan Gao, Ying Ma, Guangde Yang and Yiping Li^*

School of Pharmacy, Xi’an Jiaotong University, No. 76 Yanta West Road, Xi’an 710061, China

Molecules 2016, 21(7), 857; https://doi.org/10.3390/molecules21070857 - 29 Jun 2016

Cited by 9 | Viewed by 5860

Abstract

Phosphatidylinositol 3-kinase α (PI3Kα) is an attractive target for anticancer drug design. Liphagal, isolated from the marine sponge Aka coralliphaga, possesses the special “liphagane” meroterpenoid carbon skeleton and has been demonstrated as a PI3Kα inhibitor. Molecular docking and molecular dynamics simulations were [...] Read more.

Phosphatidylinositol 3-kinase α (PI3Kα) is an attractive target for anticancer drug design. Liphagal, isolated from the marine sponge Aka coralliphaga, possesses the special “liphagane” meroterpenoid carbon skeleton and has been demonstrated as a PI3Kα inhibitor. Molecular docking and molecular dynamics simulations were performed to explore the dynamic behaviors of PI3Kα binding with liphagal, and free energy calculations and energy decomposition analysis were carried out by use of molecular mechanics/Poisson-Boltzmann (generalized Born) surface area (MM/PB(GB)SA) methods. The results reveal that the heteroatom rich aromatic D-ring of liphagal extends towards the polar region of the binding site, and the D-ring 15-hydroxyl and 16-hydroxyl form three hydrogen bonds with Asp810 and Tyr836. The cyclohexyl A-ring projects up into the upper pocket of the lipophilic region, and the hydrophobic/van der Waals interactions with the residues Met772, Trp780, Ile800, Ile848, Val850, Met922, Phe930, Ile932 could be the key interactions for the affinity of liphagal to PI3Kα. Thus, a new strategy for the rational design of more potent analogs of liphagal against PI3Kα is provided. Our proposed PI3Kα/liphagal binding mode would be beneficial for the discovery of new active analogs of liphagal against PI3Kα. Full article

(This article belongs to the Special Issue Kinase Inhibitor Chemistry)

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16 pages, 3112 KiB

Open AccessArticle

Alendronate-Loaded Modified Drug Delivery Lipid Particles Intended for Improved Oral and Topical Administration

by Lacramioara Ochiuz^1,*

, Cristian Grigoras², Marcel Popa³, Iulian Stoleriu⁴

, Corneliu Munteanu⁵, Daniel Timofte^6,7

, Lenuta Profire⁸ and Anca Giorgiana Grigoras²

¹ Department of Pharmaceutical Technology, Faculty of Pharmacy, Grigore T. Popa University of Medicine and Pharmacy of Iasi, Universitatii Street, 16, Iasi 700115, Romania

² Petru Poni Institute of Macromolecular Chemistry, Aleea, Grigore Ghica Voda, 41A, Iasi 700487, Romania

³ Department of Natural and Synthetic Polymers, Gheorghe Asachi Technical University of Iasi, Romania, Prof. Dr. Docent Dimitrie Mangeron Avenue, 73, Iasi 700050, Romania

⁴ Faculty of Mathematics, Alexandru I. Cuza University, 11 Bvd. Carol I, Iasi 700506, Romania

⁵ Faculty of Mechanical Engineering, Gheorghe Asachi Technical University of Iasi, Romania, Prof. Dr. Docent Dimitrie Mangeron Avenue, 73, Iasi 700050, Romania

⁶ Faculty of Medicine, Grigore T.Popa University of Medicine and Pharmacy Iasi, 16 Universitatii Street, Iasi 700115, Romania

⁷ Surgery Department, Sf. Spiridon Hospital, 1 Piata Independentei, Iasi 700111, Romania

⁸ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Grigore T. Popa University of Medicine and Pharmacy of Iasi, Universitatii Street, 16, Iasi 700115, Romania

Molecules 2016, 21(7), 858; https://doi.org/10.3390/molecules21070858 - 29 Jun 2016

Cited by 30 | Viewed by 7298

Abstract

The present paper focuses on solid lipid particles (SLPs), described in the literature as the most effective lipid drug delivery systems that have been introduced in the last decades, as they actually combine the advantages of polymeric particles, hydrophilic/lipophilic emulsions and liposomes. In [...] Read more.

The present paper focuses on solid lipid particles (SLPs), described in the literature as the most effective lipid drug delivery systems that have been introduced in the last decades, as they actually combine the advantages of polymeric particles, hydrophilic/lipophilic emulsions and liposomes. In the current study, we present our most recent advances in the preparation of alendronate (AL)-loaded SLPs prepared by hot homogenization and ultrasonication using various ratios of a self-emulsifying lipidic mixture of Compritol 888, Gelucire 44/14, and Cremophor A 25. The prepared AL-loaded SLPs were investigated for their physicochemical, morphological and structural characteristics by dynamic light scattering, differential scanning calorimetry, thermogravimetric and powder X-ray diffraction analysis, infrared spectroscopy, optical and scanning electron microscopy. Entrapment efficacy and actual drug content were assessed by a validated HPLC method. In vitro dissolution tests performed in simulated gastro-intestinal fluids and phosphate buffer solution pH 7.4 revealed a prolonged release of AL of 70 h. Additionally, release kinetics analysis showed that both in simulated gastrointestinal fluids and in phosphate buffer solution, AL is released from SLPs based on equal ratios of lipid excipients following zero-order kinetics, which characterizes prolonged-release drug systems. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 1037 KiB

Open AccessArticle

A Macrosphelide as the Unexpected Product of a Pleurotus ostreatus Strain-Mediated Biotransformation of Halolactones Containing the gem-Dimethylcyclohexane Ring. Part 1

by Katarzyna Wińska^1,*, Wanda Mączka¹, Małgorzata Grabarczyk¹, Kenji Sugimoto², Yuji Matsuya², Antoni Szumny¹

and Mirosław Anioł¹

¹ Department of Chemistry, Wroclaw University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland

² Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, 930-0194 Toyama, Japan

Molecules 2016, 21(7), 859; https://doi.org/10.3390/molecules21070859 - 30 Jun 2016

Cited by 3 | Viewed by 4194

Abstract

The aim of the study was to obtain new compounds during biotransformation of two halocompounds, the δ-bromo and δ-iodo-γ-bicyclolactones 1 and 2. Unexpectedly Pleurotus ostreatus produced together with the hydroxylactone, 2-hydroxy-4,4-dimethyl-9-oxabicyclo[4.3.0]nonane-8-one (3), its own metabolite (3S,9S,15 [...] Read more.

The aim of the study was to obtain new compounds during biotransformation of two halocompounds, the δ-bromo and δ-iodo-γ-bicyclolactones 1 and 2. Unexpectedly Pleurotus ostreatus produced together with the hydroxylactone, 2-hydroxy-4,4-dimethyl-9-oxabicyclo[4.3.0]nonane-8-one (3), its own metabolite (3S,9S,15S)-(6E,12E)-3,9,15-trimethyl-4,10,16-trioxacyclohexa-deca-6,12-diene-1,5,8,11,14-pentaone (4). The method presented here, in which this macrosphelide 4 was obtained by biotransformation, has not been previously described in the literature. To the best of our knowledge, this compound has been prepared only by chemical synthesis to date. This is the first report on the possibility of the biosynthesis of this compound by the Pleurotus ostreatus strain. The conditions and factors, like temperature, salts, organic solvents, affecting the production of this macrosphelide by Pleurotus ostreatus strain were examined. The highest yield of macroshphelide production was noticed for halolactones, as well with iodide, bromide, iron and copper (2+) ions as inductors. Full article

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16 pages, 890 KiB

Open AccessArticle

Synthesis and Antimicrobial Activity of 1,2-Benzothiazine Derivatives

by Chandani Patel¹, Jatinder P. Bassin^1,*

, Mark Scott¹, Jenna Flye², Ann P. Hunter², Lee Martin³

and Madhu Goyal^1,*

¹ School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK

² EPSRC UK National Mass Spectrometry Facility, Institute of Mass Spectrometry, Swansea University Medical School, Swansea SA2 8PP, UK

³ School of Science and Technology, Nottingham Trent University, Clifton Lane, Clifton, Nottingham NG11 8NS, UK

Molecules 2016, 21(7), 861; https://doi.org/10.3390/molecules21070861 - 30 Jun 2016

Cited by 44 | Viewed by 7731

Abstract

A number of 1,2-benzothiazines have been synthesized in a three-step process. Nine chalcones 1–9 bearing methyl, fluoro, chloro and bromo substituents were chlorosulfonated with chlorosulfonic acid to generate the chalcone sulfonyl chlorides 10–18. These were converted to the [...] Read more.

A number of 1,2-benzothiazines have been synthesized in a three-step process. Nine chalcones 1–9 bearing methyl, fluoro, chloro and bromo substituents were chlorosulfonated with chlorosulfonic acid to generate the chalcone sulfonyl chlorides 10–18. These were converted to the dibromo compounds 19–27 through reaction with bromine in glacial acetic acid. Compounds 19–27 were reacted with ammonia, methylamine, ethylamine, aniline and benzylamine to generate a library of 45 1,2-benzothiazines 28–72. Compounds 28–72 were evaluated for their antimicrobial activity using broth microdilution techniques against two Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) and two Gram-negative bacteria (Proteus vulgaris and Salmonella typhimurium). The results demonstrated that none of the compounds showed any activity against Gram-negative bacteria P. vulgaris and S. typhimurium; however, compounds 31, 33, 38, 43, 45, 50, 53, 55, 58, 60, 63 and 68 showed activity against Gram-positive bacteria Bacillus subtilis and Staphylococcous aureus. The range of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) was 25–600 µg/mL, though some of the MIC and MBC concentrations were high, indicating weak activity. Structure activity relationship studies revealed that the compounds with a hydrogen atom or an ethyl group on the nitrogen of the thiazine ring exerted antibacterial activity against Gram-positive bacteria. The results also showed that the compounds where the benzene ring of the benzoyl moiety contained a methyl group or a chlorine or bromine atom in the para position showed higher antimicrobial activity. Similar influences were identified where either a bromine or chlorine atom was in the meta position. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 3041 KiB

Open AccessArticle

Pingyangmycin and Bleomycin Share the Same Cytotoxicity Pathway

by Yanli He^1,2,†, Ying Lan^1,†, Yong Liu¹, Haibo Yu³, Zhangrun Han¹, Xiulian Li¹ and Lijuan Zhang^1,2,*

¹ School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China

² Institute of Cerebrovascular Diseases, Affiliated Hospital of Qingdao University, Qingdao 266003, China

³ College of Animal Science and Technology, Northwest A&F University, Xianyang 712100, China

^† These authors contributed equally to this work.

Molecules 2016, 21(7), 862; https://doi.org/10.3390/molecules21070862 - 30 Jun 2016

Cited by 27 | Viewed by 8354

Abstract

Pingyangmycin is an anticancer drug known as bleomycin A5 (A5), discovered in the Pingyang County of Zhejiang Province of China. Bleomycin (BLM) is a mixture of mainly two compounds (A2 and B2), which is on the World Health Organization’s list of essential medicines. [...] Read more.

Pingyangmycin is an anticancer drug known as bleomycin A5 (A5), discovered in the Pingyang County of Zhejiang Province of China. Bleomycin (BLM) is a mixture of mainly two compounds (A2 and B2), which is on the World Health Organization’s list of essential medicines. Both BLM and A5 are hydrophilic molecules that depend on transporters or endocytosis receptors to get inside of cells. Once inside, the anticancer activities rely on their abilities to produce DNA breaks, thus leading to cell death. Interestingly, the half maximal inhibitory concentration (IC₅₀) of BLMs in different cancer cell lines varies from nM to μM ranges. Different cellular uptake, DNA repair rate, and/or increased drug detoxification might be some of the reasons; however, the molecules and signaling pathways responsible for these processes are largely unknown. In the current study, we purified the A2 and B2 from the BLM and tested the cytotoxicities and the molecular mechanisms of each individual compound or in combination with six different cell lines, including a Chinese hamster ovary (CHO) cell line defective in glycosaminoglycan biosynthesis. Our data suggested that glycosaminoglycans might be involved in the cellular uptake of BLMs. Moreover, both BLM and A5 shared similar signaling pathways and are involved in cell cycle and apoptosis in different cancer cell lines. Full article

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12 pages, 406 KiB

Open AccessArticle

Phenolic Profiles and Antioxidant Activity of Lotus Root Varieties

by Yang Yi^1,2, Jie Sun¹, Jun Xie¹, Ting Min^1,2, Li-Mei Wang^2,3 and Hong-Xun Wang^1,2,*

¹ College of Food Science & Engineering, Wuhan Polytechnic University, Wuhan 430023, China

² Hubei Engineering Research Center for Fresh Food, Wuhan 430023, China

³ College of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan 430023, China

Molecules 2016, 21(7), 863; https://doi.org/10.3390/molecules21070863 - 30 Jun 2016

Cited by 57 | Viewed by 8096

Abstract

Lotus root attracts increasing attention mainly because of its phenolic compounds known as natural antioxidants. Its thirteen varieties were systematically analyzed on the content, distribution, composition and antioxidant activity of phenolic compounds for a better understanding of this aquatic vegetable. The respective mean [...] Read more.

Lotus root attracts increasing attention mainly because of its phenolic compounds known as natural antioxidants. Its thirteen varieties were systematically analyzed on the content, distribution, composition and antioxidant activity of phenolic compounds for a better understanding of this aquatic vegetable. The respective mean contents of total phenolics in their flesh, peel and nodes were 1.81, 4.30 and 7.35 mg gallic acid equivalents (GAE)/g fresh weight (FW), and those of total flavonoids were 3.35, 7.69 and 15.58 mg rutin equivalents/g FW. The phenolic composition determined by a high-performance liquid chromatography method varied significantly among varieties and parts. The phenolics of flesh were mainly composed of gallocatechin and catechin; those of peel and node were mainly composed of gallocatechin, gallic acid, catechin and epicatechin. The antioxidant activities of phenolic extracts in increasing order were flesh, peel and node; their mean concentrations for 50% inhibition of 2,2-diphenyl-1-picrylhydrazyl radical were 46.00, 26.43 and 21.72 µg GAE/mL, and their mean values representing ferric reducing antioxidant power were 75.91, 87.66 and 100.43 µg Trolox equivalents/100 µg GAE, respectively. “Zoumayang”, “Baheou”, “No. 5 elian” and “Guixi Fuou” were the hierarchically clustered varieties with relatively higher phenolic content and stronger antioxidant activity as compared with the others. Especially, their nodes and peels are promising sources of antioxidants for human nutrition. Full article

(This article belongs to the Section Natural Products Chemistry)

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21 pages, 2340 KiB

Open AccessArticle

Pyridine and p-Nitrophenyl Oxime Esters with Possible Photochemotherapeutic Activity: Synthesis, DNA Photocleavage and DNA Binding Studies

by Milena Pasolli^1,†, Konstantinos Dafnopoulos^1,2,†, Nicolaos-Panagiotis Andreou¹, Panagiotis S. Gritzapis¹, Maria Koffa³, Alexandros E. Koumbis⁴, George Psomas²

and Konstantina C. Fylaktakidou^1,*

¹ Laboratory of Organic, Bioorganic and Natural Product Chemistry, Molecular Biology and Genetics Department, Democritus University of Thrace, University Campus, Dragana, GR-68100 Alexandroupolis, Greece

² Laboratory of Inorganic Chemistry, Chemistry Department, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece

³ Laboratory of Cellular Biology and Cell Cycle, Molecular Biology and Genetics Department, Democritus University of Thrace, University Campus, Dragana, GR-68100 Alexandroupolis, Greece

⁴ Laboratory of Organic Chemistry, Chemistry Department, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece

^† These authors contributed equally to this work.

Molecules 2016, 21(7), 864; https://doi.org/10.3390/molecules21070864 - 30 Jun 2016

Cited by 19 | Viewed by 8441

Abstract

Compared to standard treatments for various diseases, photochemotherapy and photo-dynamic therapy are less invasive approaches, in which DNA photocleavers represent promising tools for novel “on demand” chemotherapeutics. A series of p-nitrobenzoyl and p-pyridoyl ester conjugated aldoximes, amidoximes and ethanone oximes were [...] Read more.

Compared to standard treatments for various diseases, photochemotherapy and photo-dynamic therapy are less invasive approaches, in which DNA photocleavers represent promising tools for novel “on demand” chemotherapeutics. A series of p-nitrobenzoyl and p-pyridoyl ester conjugated aldoximes, amidoximes and ethanone oximes were subjected to UV irradiation at 312 nm with supercoiled circular plasmid DNA. The compounds which possessed appropriate properties were additionally subjected to UVA irradiation at 365 nm. The ability of most of the compounds to photocleave DNA was high at 312 nm, whereas higher concentrations were required at 365 nm as a result of their lower UV absorption. The affinity of selected compounds to calf-thymus (CT) DNA was studied by UV spectroscopy, viscosity experiments and competitive studies with ethidium bromide (EB) revealing that all compounds interacted with CT DNA. The fluorescence emission spectra of the pre-treated EB-DNA exhibited a moderate to significant quenching in the presence of the compounds indicating the binding of the compounds to CT DNA via intercalation as concluded also by DNA-viscosity experiments. For the oxime esters the DNA photocleavage and affinity studies aimed to clarify the role of the oxime nature (aldoxime, ketoxime, amidoxime) and the role of the pyridine and p-nitrophenyl moieties both as oxime substituents and ester conjugates. 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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13 pages, 1805 KiB

Open AccessArticle

Study of the UV Light Conversion of Feruloyl Amides from Portulaca oleracea and Their Inhibitory Effect on IL-6-Induced STAT3 Activation

by Joo Tae Hwang¹, Yesol Kim¹, Hyun-Jae Jang¹

, Hyun-Mee Oh¹, Chi-Hwan Lim², Seung Woong Lee^1,*

and Mun-Chual Rho^1,*

¹ Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology, 181 Ipsin-gil, Jeongeup-si, Jeonbuk 56212, Korea

² College of Agriculture and Life Sciences, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 300-764, Korea

Molecules 2016, 21(7), 865; https://doi.org/10.3390/molecules21070865 - 30 Jun 2016

Cited by 35 | Viewed by 6786

Abstract

Two new feruloyl amides, N-cis-hibiscusamide (5) and (7′S)-N-cis-feruloylnormetanephrine (9), and eight known feruloyl amides were isolated from Portulaca oleracea L. and the geometric conversion of the ten isolated feruloyl amides [...] Read more.

Two new feruloyl amides, N-cis-hibiscusamide (5) and (7′S)-N-cis-feruloylnormetanephrine (9), and eight known feruloyl amides were isolated from Portulaca oleracea L. and the geometric conversion of the ten isolated feruloyl amides by UV light was verified. The structures of the feruloyl amides were determined based on spectroscopic data and comparison with literature data. The NMR data revealed that the structures of the isolated compounds showed cis/trans-isomerization under normal laboratory light conditions. Therefore, cis and trans-isomers of feruloyl amides were evaluated for their convertibility and stability by UV light of a wavelength of 254 nm. After 96 h of UV light exposure, 23.2%–35.0% of the cis and trans-isomers were converted to trans-isomers. Long-term stability tests did not show any significant changes. Among all compounds and conversion mixtures collected, compound 6 exhibited the strongest inhibition of IL-6-induced STAT3 activation in Hep3B cells, with an IC₅₀ value of 0.2 μM. This study is the first verification of the conversion rates and an equilibrium ratio of feruloyl amides. These results indicate that this natural material might provide useful information for the treatment of various diseases involving IL-6 and STAT3. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 2495 KiB

Open AccessArticle

Photochemistry of 1,4-Dihydropyridine Derivatives: Diradical Formation, Delocalization and Trapping as a Route to Novel Tricyclic and Tetracyclic Nitrogen Heterocyclic Ring Systems

by Nader A. Al-Jalal^*, Yehia A. Ibrahim, Nouria A. Al-Awadi, Maher R. Ibrahim and Osama M. Sayed

Department of Chemistry, Faculty of Science, Kuwait University, P.O. Box 5969, Safat 13060, Kuwait

Molecules 2016, 21(7), 866; https://doi.org/10.3390/molecules21070866 - 30 Jun 2016

Cited by 6 | Viewed by 5996

Abstract

Irradiation of an acetonitrile solution of 4-aryl-3,5-dibenzoyl-1,4-dihydropyridine derivatives 1a–c and maleimides 2a–c using medium pressure Hg-arc lamp (λ > 290) nm afforded three different cycloadducts 4, 5, 6 in addition to the oxidation products 3. These [...] Read more.

Irradiation of an acetonitrile solution of 4-aryl-3,5-dibenzoyl-1,4-dihydropyridine derivatives 1a–c and maleimides 2a–c using medium pressure Hg-arc lamp (λ > 290) nm afforded three different cycloadducts 4, 5, 6 in addition to the oxidation products 3. These results indicate that compounds 1a–c undergoes intermolecular cycloaddition reaction through three biradical intermediates and behave photochemically different than those reported previously for the analogous 3,5-diacetyl and 3,5-dicarboxylic acid derivatives. The present work also offers simple access to novel tricyclic and tetracyclic nitrogen heterocyclic ring systems of potential biological and synthetic applications. The structure of the photoproducts was established spectroscopically and by single crystal X-ray crystallography. Full article

(This article belongs to the Special Issue Photoactive Molecules)

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14 pages, 1597 KiB

Open AccessArticle

Assessing and Broadening Genetic Diversity of Elymus sibiricus Germplasm for the Improvement of Seed Shattering

by Zongyu Zhang, Junchao Zhang, Xuhong Zhao, Wengang Xie^* and Yanrong Wang^*

The State Key Laboratory of Grassland Agro-ecosystems, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730020, China

Molecules 2016, 21(7), 869; https://doi.org/10.3390/molecules21070869 - 1 Jul 2016

Cited by 12 | Viewed by 5712

Abstract

Siberian wild rye (Elymus sibiricus L.) is an important native grass in the Qinghai-Tibet Plateau of China. It is difficult to grow for commercial seed production, since seed shattering causes yield losses during harvest. Assessing the genetic diversity and relationships among germplasm [...] Read more.

Siberian wild rye (Elymus sibiricus L.) is an important native grass in the Qinghai-Tibet Plateau of China. It is difficult to grow for commercial seed production, since seed shattering causes yield losses during harvest. Assessing the genetic diversity and relationships among germplasm from its primary distribution area contributes to evaluating the potential for its utilization as a gene pool to improve the desired agronomic traits. In the study, 40 EST-SSR primers were used to assess the genetic diversity and population structure of 36 E. sibiricus accessions with variation of seed shattering. A total of 380 bands were generated, with an average of 9.5 bands per primer. The polymorphic information content (PIC) ranged from 0.23 to 0.50. The percentage of polymorphic bands (P) for the species was 87.11%, suggesting a high degree of genetic diversity. Based on population structure analysis, four groups were formed, similar to results of principal coordinate analysis (PCoA). The molecular variance analysis (AMOVA) revealed the majority of genetic variation occurred within geographical regions (83.40%). Two genotypes from Y1005 and ZhN06 were used to generate seven F₁ hybrids. The molecular and morphological diversity analysis of F₁ population revealed rich genetic variation and high level of seed shattering variation in F₁ population, resulting in significant improvement of the genetic base and desired agronomic traits. Full article

(This article belongs to the Section Molecular Diversity)

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18 pages, 6153 KiB

Open AccessFeature PaperArticle

Multivariate Chemical Image Fusion of Vibrational Spectroscopic Imaging Modalities

by Aoife A. Gowen^*

and Ronan M. Dorrepaal

UCD School of Biosystems and Food Engineering, College of Engineering and Architecture, University College Dublin, Belfield, Dublin 4, Ireland

Molecules 2016, 21(7), 870; https://doi.org/10.3390/molecules21070870 - 2 Jul 2016

Cited by 18 | Viewed by 5449

Abstract

Chemical image fusion refers to the combination of chemical images from different modalities for improved characterisation of a sample. Challenges associated with existing approaches include: difficulties with imaging the same sample area or having identical pixels across microscopic modalities, lack of prior knowledge [...] Read more.

Chemical image fusion refers to the combination of chemical images from different modalities for improved characterisation of a sample. Challenges associated with existing approaches include: difficulties with imaging the same sample area or having identical pixels across microscopic modalities, lack of prior knowledge of sample composition and lack of knowledge regarding correlation between modalities for a given sample. In addition, the multivariate structure of chemical images is often overlooked when fusion is carried out. We address these challenges by proposing a framework for multivariate chemical image fusion of vibrational spectroscopic imaging modalities, demonstrating the approach for image registration, fusion and resolution enhancement of chemical images obtained with IR and Raman microscopy. Full article

(This article belongs to the Special Issue Vibrational Spectroscopic Imaging and Mapping)

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10 pages, 2789 KiB

Open AccessArticle

Carlina acaulis Exhibits Antioxidant Activity and Counteracts Aβ Toxicity in Caenorhabditis elegans

by Pille Link^1,*

, Kevin Roth^1,2, Frank Sporer¹ and Michael Wink^1,*

¹ Institute of Pharmacy and Molecular Biology, Heidelberg University, Heidelberg 69120, Germany

² Jacqui Wood Cancer Centre, Division of Cancer Research, School of Medicine, University of Dundee, Dundee, Scotland DD1 9SY, UK

Molecules 2016, 21(7), 871; https://doi.org/10.3390/molecules21070871 - 2 Jul 2016

Cited by 31 | Viewed by 7575

Abstract

Carlina acaulis is a medicinal plant that has shown antioxidant activity in in vitro studies, but to date no corresponding in vivo data is available. Therefore, in the present study the antioxidant activity and its impact in counteracting Aβ toxicity were studied in [...] Read more.

Carlina acaulis is a medicinal plant that has shown antioxidant activity in in vitro studies, but to date no corresponding in vivo data is available. Therefore, in the present study the antioxidant activity and its impact in counteracting Aβ toxicity were studied in the Caenorhabditis elegans model. A dichloromethane extract of the roots of C. acaulis was prepared and characterised via gas-liquid-chromatography/mass-spectrometry (GLC-MS). The in vitro antioxidant activity was confirmed via 2,2-diphenyl-1-picrylhydracyl assay. The extract was further separated by thin layer chromatography into two fractions, one of which was a fraction of the dichloromethane extract of C. acaulis containing mostly Carlina oxide (CarOx). Different strains of C. elegans were employed to study the expression of hsp-16.2p::GFP as a marker for oxidative stress, delocalisation of the transcription factor DAF-16 as a possible mechanism of antioxidant activity, the effect of the drug under lethal oxidative stress, and the effect against beta-amyloid (Aβ) toxicity in a paralysis assay. The C. acaulis extract and CarOx showed high antioxidant activity (stress reduction by 47% and 64%, respectively) in C. elegans and could activate the transcription factor DAF-16 which directs the expression of anti-stress genes. In paralysis assay, only the total extract was significantly active, delaying paralysis by 1.6 h. In conclusion, in vivo antioxidant activity was shown for C. acaulis for the first time in the C. elegans model. The active antioxidant compound is Carlina oxide. This activity, however, is not sufficient to counteract Aβ toxicity. Other mechanisms and possibly other active compounds are involved in this effect. Full article

(This article belongs to the Collection Bioactive Compounds)

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14 pages, 4307 KiB

Open AccessArticle

18α-Glycyrrhetinic Acid Induces Apoptosis of HL-60 Human Leukemia Cells through Caspases- and Mitochondria-Dependent Signaling Pathways

by Yi-Chang Huang¹, Chao-Lin Kuo², Kung-Wen Lu³, Jen-Jyh Lin⁴, Jiun-Long Yang², Rick Sai-Chuen Wu^5,6, Ping-Ping Wu^7,*,† and Jing-Gung Chung^1,8,*,†

¹ Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan

² Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan

³ College of Chinese Medicine, School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung 404, Taiwan

⁴ Division of Cardiology, China Medical University Hospital, Taichung 404, Taiwan

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

⁶ Department of Medicine, China Medical University, Taichung 404, Taiwan

⁷ School of Pharmacy, China Medical University, Taichung 404, Taiwan

⁸ Department of Biotechnology, Asia University, Taichung 413, Taiwan

^† These authors contributed equally to this work.

Molecules 2016, 21(7), 872; https://doi.org/10.3390/molecules21070872 - 1 Jul 2016

Cited by 34 | Viewed by 8561

Abstract

In this study we investigate the molecular mechanisms of caspases and mitochondria in the extrinsic and intrinsic signal apoptosis pathways in human leukemia HL-60 cells after in vitro exposure to 18α-glycyrrhetinic acid (18α-GA). Cells were exposed to 18α-GA at various concentrations for various [...] Read more.

In this study we investigate the molecular mechanisms of caspases and mitochondria in the extrinsic and intrinsic signal apoptosis pathways in human leukemia HL-60 cells after in vitro exposure to 18α-glycyrrhetinic acid (18α-GA). Cells were exposed to 18α-GA at various concentrations for various time periods and were harvested for flow cytometry total viable cell and apoptotic cell death measurements. Cells treated with 18α-GA significantly inhibited cell proliferation and induced cell apoptosis in a dose-dependent manner, with an IC₅₀ value of 100 μM at 48 h. The cell growth inhibition resulted in induction of apoptosis and decreased the mitochondria membrane potential (ΔΨ_m) and increased caspase-8, -9 and -3 activities. Furthermore, cytochrome c and AIF were released from mitochondria, as shown by western blotting and confirmed by confocal laser microscopy. Western blotting showed that 18α-GA increased the levels of pro-apoptotic proteins such as Bax and Bid and decreased the anti-apoptotic proteins such as Bcl-2 and Bcl-xl, furthermore, results also showed that 18α-GA increased Fas and Fas-L which are associated with surface death receptor in HL-60 cells. Based on those observations, the present study supports the hypothesis that 18α-GA-induced apoptosis in HL-60 cells involves the activation of the both extrinsic and intrinsic apoptotic pathways. Full article

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12 pages, 2458 KiB

Open AccessArticle

Controlled Release of Nor-β-lapachone by PLGA Microparticles: A Strategy for Improving Cytotoxicity against Prostate Cancer Cells

by Marcilia P. Costa^1,2, Anderson C. S. Feitosa¹, Fátima C. E. Oliveira¹, Bruno C. Cavalcanti¹, Eufrânio N. Da Silva³, Gleiston G. Dias³, Francisco A. M. Sales⁴, Bruno L. Sousa⁴, Ito L. Barroso-Neto⁵, Cláudia Pessoa^1,6, Ewerton W. S. Caetano^7,*, Stefano Di Fiore⁸, Rainer Fischer^8,9, Luiz O. Ladeira¹⁰ and Valder N. Freire⁵

¹ Department of Physiology and Pharmacology, Federal University of Ceará, 60430-270 Fortaleza, CE, Brazil

² Department of Pharmacy, Federal University of Piauí, 64049-550 Teresina, PI, Brazil

³ Department of Chemistry, Federal University of Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil

⁴ Department of Physics, Federal University of Ceará, 60455-760 Fortaleza, CE, Brazil

⁵ Department of Analytical Chemistry and Physical Chemistry, Federal University of Ceará, 60455-760 Fortaleza, CE, Brazil

⁶ Oswaldo Cruz Foundation (Fiocruz), 60180-900 Fortaleza, CE, Brazil

⁷ Department of Secondary School and Teachers College, Federal Institute of Ceará, 60040-531 Fortaleza, CE, Brazil

⁸ Fraunhofer Institute for Molecular Biology and Applied Ecology IME, 52074, Aachen, Germany

⁹ Institute for Molecular Biotechnology, RWTH Aachen University, 52074 Aachen, Germany

¹⁰ Department of Physics, Federal University of Minas Gerais, 31340-550 Belo Horizonte, MG, Brazil

Molecules 2016, 21(7), 873; https://doi.org/10.3390/molecules21070873 - 2 Jul 2016

Cited by 22 | Viewed by 7508

Abstract

Prostate cancer is one of the most common malignant tumors in males and it has become a major worldwide public health problem. This study characterizes the encapsulation of Nor-β-lapachone (NβL) in poly(d,l-lactide-co-glycolide) (PLGA) microcapsules and evaluates the cytotoxicity of [...] Read more.

Prostate cancer is one of the most common malignant tumors in males and it has become a major worldwide public health problem. This study characterizes the encapsulation of Nor-β-lapachone (NβL) in poly(d,l-lactide-co-glycolide) (PLGA) microcapsules and evaluates the cytotoxicity of the resulting drug-loaded system against metastatic prostate cancer cells. The microcapsules presented appropriate morphological features and the presence of drug molecules in the microcapsules was confirmed by different methods. Spherical microcapsules with a size range of 1.03 ± 0.46 μm were produced with an encapsulation efficiency of approximately 19%. Classical molecular dynamics calculations provided an estimate of the typical adsorption energies of NβL on PLGA. Finally, the cytotoxic activity of NβL against PC3M human prostate cancer cells was demonstrated to be significantly enhanced when delivered by PLGA microcapsules in comparison with the free drug. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 1719 KiB

Open AccessArticle

Enhancement of Exposure and Reduction of Elimination for Paeoniflorin or Albiflorin via Co-Administration with Total Peony Glucosides and Hypoxic Pharmacokinetics Comparison

by Weizhe Xu^1,†, Yan Zhao^1,†, Yi Qin¹, Beikang Ge¹, Wenwen Gong¹, Yingting Wu², Xiaorong Li^1,3, Yuming Zhao^1,3, Pingxiang Xu^1,3 and Ming Xue^1,3,*

¹ Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China

² Core Facilities Center, Capital Medical University, Beijing 100069, China

³ Beijing Laboratory for Biomedical Detection Technology and Instrument, Beijing 100069, China

^† These authors contributed equally to this work.

Molecules 2016, 21(7), 874; https://doi.org/10.3390/molecules21070874 - 1 Jul 2016

Cited by 20 | Viewed by 6444

Abstract

There is evidence suggesting that herbal extracts demonstrate greater bioactivities than their isolated constituents at an equivalent dose. This phenomenon could be attributed to the absence of interacting substances present in the extracts. By measuring the pharmacokinetic parameters of paeoniflorin (PF) and albiflorin [...] Read more.

There is evidence suggesting that herbal extracts demonstrate greater bioactivities than their isolated constituents at an equivalent dose. This phenomenon could be attributed to the absence of interacting substances present in the extracts. By measuring the pharmacokinetic parameters of paeoniflorin (PF) and albiflorin (AF) after being orally administered to rats in isolated form, in combination with each other and within total peony glucosides (TPG), respectively, the current study aimed to identify positive pharmacokinetic interactions between components of peony radix extracts. Moreover, the pharmacokinetic profiles of PF and AF under normoxia and hypoxia were also investigated and compared. In order to achieve these goals, a highly sensitive and reproducible ultra-peformance liquid chromatography–mass spectrometry (UPLC-MS) method was developed and validated for simultaneously quantitation of PF and AF in rat plasma. This study found that compared with that of single component (PF/AF), the exposure of PF in rat plasma after combination administration or TPG administration was significantly increased, meanwhile the elimination of PF/AF was remarkably reduced. It was also noticed that AUC and C_max of PF in hypoxia rats were significantly decreased compared with that of normaxia rats, suggesting that there was a decreased exposure of PF in rats under hypoxia. The current study, for the first time, revealed the pharmacokinetic interactions between PF/AF and other constitutes in TGP and the pharmacokinetic profiles of PF and AF under hypoxia. In view of the current findings, it could be supposed that the clinical performance of total peony glucosides would be better than that of single constitute (PF/AF). The outcomes of this animal study are expected to serve as a basis for development of clinical guidelines on total peony glucosides usage. Full article

(This article belongs to the Collection Bioactive Compounds)

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15 pages, 2682 KiB

Open AccessArticle

Design and Stereochemical Research (DFT, ECD and Crystal Structure) of Novel Bedaquiline Analogs as Potent Antituberculosis Agents

by Yiding Geng¹, Linwei Li¹, Chengjun Wu¹, Yumeng Chi¹, Zhen Li¹, Wei Xu^2,* and Tiemin Sun^1,*

¹ Key Laboratory of Structure-Based Drug Design and Discovery, Shenyang Pharmaceutical University, Ministry of Education, Shenyang 110016, China

² School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China

Molecules 2016, 21(7), 875; https://doi.org/10.3390/molecules21070875 - 4 Jul 2016

Cited by 7 | Viewed by 6150

Abstract

A series of bedaquiline analogs containing H-bond donors were designed as anti-Mycobacterium tuberculosis drugs. A pair of diastereoisomers (R/S- and S/S-isomers) was selected from these designed compounds for synthetic and stereochemical research. The title compounds were synthesized from chiral [...] Read more.

A series of bedaquiline analogs containing H-bond donors were designed as anti-Mycobacterium tuberculosis drugs. A pair of diastereoisomers (R/S- and S/S-isomers) was selected from these designed compounds for synthetic and stereochemical research. The title compounds were synthesized from chiral precursors for the first time and the absolute configurations (ACs) were determined by electronic circular dichroism (ECD) with quantum chemical calculations. Moreover, a single crystal of the S/S compound was obtained for X-ray diffraction analysis, and the crystal structure showed high consistency with the geometry, confirming the reliability of ACs obtained by ECD analyses and theoretical simulation. Furthermore, the effect of stereochemistry on the anti-tuberculosis activity was investigated. The MICs of the R/S- and S/S-isomers against Mycobacterium phlei 1180 are 9.6 and 32.1 μg·mL⁻¹, respectively. Finally, molecular docking was carried out to evaluate the inhibitory nature and binding mode differences between diastereoisomers. Full article

(This article belongs to the Section Medicinal Chemistry)

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14 pages, 4853 KiB

Open AccessArticle

Design, Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Selective PI3Kβ Inhibitors

by Shuang Cao^1,2,†, Ruiyuan Cao^1,†, Xialing Liu², Xiang Luo² and Wu Zhong^1,*

¹ Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China

² Hubei Key Laboratory of Novel Chemical Reactor and Green Chemical Technology, Wuhan Institute of Technology, Wuhan 430073, Hubei, China

^† These authors contributed equally to this work.

Molecules 2016, 21(7), 876; https://doi.org/10.3390/molecules21070876 - 2 Jul 2016

Cited by 24 | Viewed by 7159

Abstract

A novel series of PI3Kβ (Phosphatidylinositol-3-kinases beta subunit) inhibitors with the structure of benzothiazole scaffold have been designed and synthesized. All the compounds have been evaluated for inhibitory activities against PI3Kα, β, γ, δ and mTOR (Mammalian target of rapamycin). Two superior compounds [...] Read more.

A novel series of PI3Kβ (Phosphatidylinositol-3-kinases beta subunit) inhibitors with the structure of benzothiazole scaffold have been designed and synthesized. All the compounds have been evaluated for inhibitory activities against PI3Kα, β, γ, δ and mTOR (Mammalian target of rapamycin). Two superior compounds have been further evaluated for the IC₅₀ values against PI3Ks/mTOR. The most promising compound 11 displays excellent anti-proliferative activity and selectivity in multiple cancer cell lines, especially in the prostate cancer cell line. Docking studies indicate the morpholine group in 2-position of benzothiazole is necessary for the potent antitumor activity, which confirms our design is reasonable. Full article

(This article belongs to the Special Issue Kinase Inhibitor Chemistry)

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10 pages, 1765 KiB

Open AccessArticle

Lead Discovery of Type II BRAF V600E Inhibitors Targeting the Structurally Validated DFG-Out Conformation Based upon Selected Fragments

by Qingwen Zhang^1,*, Xuejin Zhang² and Qidong You³

¹ Division of Medicinal Chemistry, Shanghai Institute of Pharmaceutical Industry, 285 Gebaini Road, Pudong, Shanghai 201203, China

² State Key Laboratory of Lead Compound Research, WuXi AppTec, 288 Fute Zhong Road, Waigaoqiao Pilot Free Trade Zone, Pudong, Shanghai 200131, China

³ Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, 24 Tongjia Xiang, Gulou, Nanjing 210009, Jiangsu, China

Molecules 2016, 21(7), 879; https://doi.org/10.3390/molecules21070879 - 16 Jul 2016

Cited by 10 | Viewed by 9042

Abstract

The success of the first approved kinase inhibitor imatinib has spurred great interest in the development of type II inhibitors targeting the inactive DFG-out conformation, wherein the Phe of the DFG motif at the start of the activation loop points into the ATP [...] Read more.

The success of the first approved kinase inhibitor imatinib has spurred great interest in the development of type II inhibitors targeting the inactive DFG-out conformation, wherein the Phe of the DFG motif at the start of the activation loop points into the ATP binding site. Nevertheless, kinase inhibitors launched so far are heavily biased toward type I inhibitors targeting the active DFG-in conformation, wherein the Phe of the DFG motif flips by approximately 180° relative to the inactive conformation, resulting in Phe and Asp swapping their positions. Data recently obtained with structurally validated type II inhibitors supported the conclusion that type II inhibitors are more selective than type I inhibitors. In our type II BRAF V600E inhibitor lead discovery effort, we identified phenylaminopyrimidine (PAP) and unsymmetrically disubstituted urea as two fragments that are frequently presented in FDA-approved protein kinase inhibitors. We therefore defined PAP and unsymmetrically disubstituted urea as privileged fragments for kinase drug discovery. A pharmacophore for type II inhibitors, 4-phenylaminopyrimidine urea (4-PAPU), was assembled based upon these privileged fragments. Lead compound SI-046 with BRAF V600E inhibitory activity comparable to the template compound sorafenib was in turn obtained through preliminary structure–activity relationship (SAR) study. Molecular docking suggested that SI-046 is a bona fide type II kinase inhibitor binding to the structurally validated “classical DFG-out” conformation of BRAF V600E. Our privileged fragments-based approach was shown to efficiently deliver a bona fide type II kinase inhibitor lead. In essence, the theme of this article is to showcase the strategy and rationale of our approach. Full article

(This article belongs to the Special Issue Developments in Fragment-Based Lead Discovery)

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13 pages, 3173 KiB

Open AccessArticle

Myricitrin Attenuates High Glucose-Induced Apoptosis through Activating Akt-Nrf2 Signaling in H9c2 Cardiomyocytes

by Bin Zhang^1,2,3,4,†

, Yaping Chen^5,†, Qiang Shen⁶, Guiyan Liu⁵, Jingxue Ye^1,2,3,4, Guibo Sun^1,2,3,4,* and Xiaobo Sun^1,2,3,4,*

¹ Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China

² Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China

³ Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing 100193, China

⁴ Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glyeolipid Metabolism Disorder Disease, State Administration of Traditional Chinese Medicine, Beijing 100193, China

⁵ School of Life Science, Beijing Institute of Technology, Beijing 100081, China

⁶ Center of Research and Development on Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, China

^† These authors contributed equally to this work.

Molecules 2016, 21(7), 880; https://doi.org/10.3390/molecules21070880 - 5 Jul 2016

Cited by 53 | Viewed by 11827

Abstract

Hyperglycemia, as well as diabetes mellitus, has been shown to trigger cardiac cell apoptosis. We have previously demonstrated that myricitrin prevents endothelial cell apoptosis. However, whether myricitrin can attenuate H9c2 cell apoptosis remains unknown. In this study, we established an experiment model in [...] Read more.

Hyperglycemia, as well as diabetes mellitus, has been shown to trigger cardiac cell apoptosis. We have previously demonstrated that myricitrin prevents endothelial cell apoptosis. However, whether myricitrin can attenuate H9c2 cell apoptosis remains unknown. In this study, we established an experiment model in H9c2 cells exposed to high glucose. We tested the hypothesis that myricitrin may inhibit high glucose (HG)-induced cardiac cell apoptosis as determined by TUNEL staining. Furthermore, myricitrin promoted antioxidative enzyme production, suppressed high glucose-induced reactive oxygen species (ROS) production and decreased mitochondrial membrane potential (MMP) in H9c2 cells. This agent significantly inhibited apoptotic protein expression, activated Akt and facilitated the transcription of NF-E2-related factor 2 (Nrf2)-mediated protein (heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO-1) expression as determined by Western blotting. Significantly, an Akt inhibitor (LY294002) or HO-1 inhibitor (ZnPP) not only inhibited myricitrin-induced HO-1/NQO-1 upregulation but also alleviated its anti-apoptotic effects. In summary, these observations demonstrate that myricitrin activates Nrf2-mediated anti-oxidant signaling and attenuates H9c2 cell apoptosis induced by high glucose via activation of Akt signaling. Full article

(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)

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11 pages, 16604 KiB

Open AccessArticle

A PDMS-Based Microfluidic Hanging Drop Chip for Embryoid Body Formation

by Huei-Wen Wu¹, Yi-Hsing Hsiao², Chih-Chen Chen^2,3

, Shaw-Fang Yet⁴ and Chia-Hsien Hsu^1,2,*

¹ Institutes of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan 35053, Taiwan

² Institute of Nano Engineering and MicroSystems, National Tsing Hua University, Hsinchu 30013, Taiwan

³ Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan

⁴ Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan 35053, Taiwan

Molecules 2016, 21(7), 882; https://doi.org/10.3390/molecules21070882 - 6 Jul 2016

Cited by 33 | Viewed by 9849

Abstract

The conventional hanging drop technique is the most widely used method for embryoid body (EB) formation. However, this method is labor intensive and limited by the difficulty in exchanging the medium. Here, we report a microfluidic chip-based approach for high-throughput formation of EBs. [...] Read more.

The conventional hanging drop technique is the most widely used method for embryoid body (EB) formation. However, this method is labor intensive and limited by the difficulty in exchanging the medium. Here, we report a microfluidic chip-based approach for high-throughput formation of EBs. The device consists of microfluidic channels with 6 × 12 opening wells in PDMS supported by a glass substrate. The PDMS channels were fabricated by replicating polydimethyl-siloxane (PDMS) from SU-8 mold. The droplet formation in the chip was tested with different hydrostatic pressures to obtain optimal operation pressures for the wells with 1000 μm diameter openings. The droplets formed at the opening wells were used to culture mouse embryonic stem cells which could subsequently developed into EBs in the hanging droplets. This device also allows for medium exchange of the hanging droplets making it possible to perform immunochemistry staining and characterize EBs on chip. Full article

(This article belongs to the Special Issue Micro/Nano Fluidics and Bio-MEMS)

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9 pages, 1185 KiB

Open AccessArticle

Biotransformation of Resveratrol: New Prenylated trans-Resveratrol Synthesized by Aspergillus sp. SCSIOW2

by Liyan Wang^1,2,*, Yanhua Wu^1,2, Yongtao Chen^1,2, Jiaxin Zou^1,2 and Xiaofan Li^1,2,*

¹ Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China

² Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China

Molecules 2016, 21(7), 883; https://doi.org/10.3390/molecules21070883 - 6 Jul 2016

Cited by 10 | Viewed by 5980

Abstract

Arahypin-16 (1), a new prenylated resveratrol with a unique dihydrobenzofuran ring, has been isolated as a microbial metabolite of resveratrol (2) from whole-cell fermentation of Aspergillus sp. SCSIOW2. The stereochemistry of 1 was determined by ECD calculations. 1 showed [...] Read more.

Arahypin-16 (1), a new prenylated resveratrol with a unique dihydrobenzofuran ring, has been isolated as a microbial metabolite of resveratrol (2) from whole-cell fermentation of Aspergillus sp. SCSIOW2. The stereochemistry of 1 was determined by ECD calculations. 1 showed about half of the extracellular radical scavenging effect (IC₅₀ = 161.4 μM) compared with resveratrol (IC₅₀ = 80.5 μM), while on biomembranes it exhibited the same range of protection effects against free radicals generated from AAPH (IC₅₀ = 78.6 μM and 87.9 μM). Full article

(This article belongs to the Special Issue Improvements for Resveratrol Efficacy)

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13 pages, 4087 KiB

Open AccessArticle

The Pleiotropic Antibacterial Mechanisms of Ursolic Acid against Methicillin-Resistant Staphylococcus aureus (MRSA)

by Chao-Min Wang

, Yun-Lian Jhan, Shang-Jie Tsai and Chang-Hung Chou^*

Research Center for Biodiversity, China Medical University, Taichung 40402, Taiwan

Molecules 2016, 21(7), 884; https://doi.org/10.3390/molecules21070884 - 7 Jul 2016

Cited by 39 | Viewed by 10403

Abstract

(1) Background: Several triterpenoids were found to act synergistically with classes of antibiotic, indicating that plant-derived chemicals have potential to be used as therapeutics to enhance the activity of antibiotics against multidrug-resistant pathogens. However, the mode of action of triterpenoids against bacterial pathogens [...] Read more.

(1) Background: Several triterpenoids were found to act synergistically with classes of antibiotic, indicating that plant-derived chemicals have potential to be used as therapeutics to enhance the activity of antibiotics against multidrug-resistant pathogens. However, the mode of action of triterpenoids against bacterial pathogens remains unclear. The objective of this study is to evaluate the interaction between ursolic acid against methicillin-resistant Staphylococcus aureus (MRSA); (2) Methods: The ability of ursolic acid to damage mammalian and bacterial membranes was examined. The proteomic response of methicillin-resistant S. aureus in ursolic acid treatment was investigated using two-dimensional (2D) proteomic analysis; (3) Results: Ursolic acid caused the loss of staphylococcal membrane integrity without hemolytic activity. The comparison of the protein pattern of ursolic acid–treated and normal MRSA cells revealed that ursolic acid affected a variety of proteins involved in the translation process with translational accuracy, ribonuclease and chaperon subunits, glycolysis and oxidative responses; (4) Conclusion: The mode of action of ursolic acid appears to be the influence on the integrity of the bacterial membrane initially, followed by inhibition of protein synthesis and the metabolic pathway. These findings reflect that the pleiotropic effects of ursolic acid against MRSA make it a promising antibacterial agent in pharmaceutical research. Full article

(This article belongs to the Collection Antibiotics & Superbugs: New Strategies to Combat Antimicrobial Resistance)

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13 pages, 6454 KiB

Open AccessArticle

Using Low Temperature Photoluminescence Spectroscopy to Investigate CH₃NH₃PbI₃ Hybrid Perovskite Degradation

by Khaoula Jemli^1,2, Hiba Diab¹, Ferdinand Lédée^1,2, Gaelle Trippé-Allard¹, Damien Garrot³, Bernard Geffroy⁴, Jean-Sébastien Lauret¹, Pierre Audebert^2,* and Emmanuelle Deleporte^1,*

¹ Laboratoire Aimé Cotton, Ecole Normale Supérieure de Cachan, CNRS, Université Paris-Sud, Université Paris-Saclay, Bât 505 Campus d’Orsay, 91405 Orsay, France

² Laboratoire de Photophysique et Photochimie Supramoléculaires et Macromoléculaires de l’Ecole Normale Supérieure de Cachan, 61 Avenue du Président Wilson, 94235 Cachan, France

³ Groupe d’Etudes de la Matière Condensée (GEMaC), CNRS, Université de Versailles Saint-Quentin-en-Yvelines, Université Paris-Saclay, 45 Avenue des Etats-Unis, 78035 Versailles Cedex, France

⁴ Laboratory of Innovation in Surface Chemistry and Nanosciences, NIMBE, CEA, CNRS, Université Paris-Saclay, CEA Saclay, 91191 Gif-sur-Yvette Cedex, France

Molecules 2016, 21(7), 885; https://doi.org/10.3390/molecules21070885 - 8 Jul 2016

Cited by 18 | Viewed by 10086

Abstract

Investigating the stability and evaluating the quality of the CH₃NH₃PbI₃ perovskite structures is quite critical both to the design and fabrication of high-performance perovskite devices and to fundamental studies of the photophysics of the excitons. In particular, it [...] Read more.

Investigating the stability and evaluating the quality of the CH₃NH₃PbI₃ perovskite structures is quite critical both to the design and fabrication of high-performance perovskite devices and to fundamental studies of the photophysics of the excitons. In particular, it is known that, under ambient conditions, CH₃NH₃PbI₃ degrades producing some PbI₂. We show here that low temperature Photoluminescence (PL) spectroscopy is a powerful tool to detect PbI₂ traces in hybrid perovskite layers and single crystals. Because PL spectroscopy is a signal detection method on a black background, small PbI₂ traces can be detected, when other methods currently used at room temperature fail. Our study highlights the extremely high stability of the single crystals compared to the thin layers and defects and grain boundaries are thought to play an important role in the degradation mechanism. Full article

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

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18 pages, 2237 KiB

Open AccessArticle

Gingerol Synergizes the Cytotoxic Effects of Doxorubicin against Liver Cancer Cells and Protects from Its Vascular Toxicity

by Fahad A. Al-Abbasi¹, Eman A. Alghamdi¹, Mohammed A. Baghdadi^1,2

, Abdulmohsin J. Alamoudi³, Ali M. El-Halawany^4,5, Hany M. El-Bassossy^3,6, Ali H. Aseeri⁷ and Ahmed M. Al-Abd^3,8,*

¹ Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21523, Saudi Arabia

² Research Centre, King Faisal Specialist Hospital and Research Centre, Jeddah 21499, Saudi Arabia

³ Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia

⁴ Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia

⁵ Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt

⁶ Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt

⁷ Ministry of Health, Jeddah 21484, Saudi Arabia

⁸ Department of Pharmacology, Medical Division, National Research Centre, Giza 12622, Egypt

Molecules 2016, 21(7), 886; https://doi.org/10.3390/molecules21070886 - 8 Jul 2016

Cited by 48 | Viewed by 9520

Abstract

Hydroxyphenylalkanes and diarylheptanoids possess potential therapeutic value in different pathophysiological conditions, such as malignancy. In the current study, naturally isolated hydroxyphenylalkane and diarylheptanoid compounds were investigated for potential chemo-modulatory effects in addition to potential vascular protective roles with doxorubicin. Diarylheptanoids showed stronger antioxidant [...] Read more.

Hydroxyphenylalkanes and diarylheptanoids possess potential therapeutic value in different pathophysiological conditions, such as malignancy. In the current study, naturally isolated hydroxyphenylalkane and diarylheptanoid compounds were investigated for potential chemo-modulatory effects in addition to potential vascular protective roles with doxorubicin. Diarylheptanoids showed stronger antioxidant effects, in comparison to hydroxyphenylalkanes, as demonstrated by DPPH assay and amelioration of CCl₄-induced disturbed intracellular GSH/GSSG balance. Shogaol and 4′-methoxygingerol showed considerable cytotoxic effects against HCT116, HeLa, HepG2 and MCF7 cells, with IC₅₀ values ranging from 3.1 to 19.4 µM. Gingerol significantly enhanced the cytotoxic profile of doxorubicin against HepG₂ and Huh7, cells decreasing its IC₅₀s by 10- and 4-fold, respectively. Cell cycle distribution was studied using DNA cytometry. Doxorubicin alone induced cell accumulation at S-phase and G₂/M-phase, while in combination with gingerol it significantly induced cell cycle arrest at the G₂/M-phase. Additionally, the vascular protective effect of gingerol against doxorubicin (10 µM) was examined on isolated aortic rings. Co-incubation with 6-gingerol (30 µM) completely blocked the exaggerated vasoconstriction and impaired vascular relaxation induced by doxorubicin. In conclusion, despite its relatively weak antioxidant properties, gingerol protected from DOX-induced vascular damage, apparently not through a ROS scavenging mechanism. Besides, gingerol synergized the cytotoxic effects of DOX against liver cancer cells without influencing the cellular pharmacokinetics. Full article

(This article belongs to the Collection Bioactive Compounds)

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11 pages, 872 KiB

Open AccessArticle

Inhibitory Activities of Phenolic Compounds Isolated from Adina rubella Leaves Against 5α-Reductase Associated with Benign Prostatic Hypertrophy

by Jun Yin, Jun Hyeok Heo, Yoon Jeong Hwang, Thi Tam Le and Min Won Lee^*

Laboratory of Pharmacognosy and Natural Product Derived Medicine, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea

Molecules 2016, 21(7), 887; https://doi.org/10.3390/molecules21070887 - 7 Jul 2016

Cited by 17 | Viewed by 5716

Abstract

Adina rubella Hance (AR), a plant native to Korea, has been used as traditional medicine for dysentery, eczema, intoxication, and external hemorrhages. Previous phytochemical studies of AR have reported several components, including terpenoids, phenolics, and alkaloids. The current study evaluated the anti-oxidative and [...] Read more.

Adina rubella Hance (AR), a plant native to Korea, has been used as traditional medicine for dysentery, eczema, intoxication, and external hemorrhages. Previous phytochemical studies of AR have reported several components, including terpenoids, phenolics, and alkaloids. The current study evaluated the anti-oxidative and anti-inflammatory activities and 5α-reductase inhibition of isolated compounds of AR leaves to find a potential therapeutic agent for benign prostatic hypertrophy (BPH). Repeated chromatographic isolation of an 80% acetone extract of AR leaves yielded seven phenolic compounds: caffeic acid (1), chlorogenic acid (2), methyl chlorogenate (3), quercetin-3-rutinoside (4), kaempferol-3-O-α-l-rhamnopyranosyl-(1→6)-β-d-glucopyranoside (5), hyperoside (6), and grandifloroside (7). Compound 7 is a novel compound in AR. Caffeoyl derivatives 1–3 and 7 showed good anti-oxidative activities. In particular, caffeic acid (1) and grandifloroside (7) showed potent anti-inflammatory activities, and 7 also exhibited potent inhibitory activity against TNF-α and 5α-reductase. Our results show that the extract and grandifloroside (7) from leaves of AR might be developed as a source of potent anti-oxidative and anti-inflammatory agents and therapeutic agent for BPH. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 3706 KiB

Open AccessArticle

β-Keto-enol Tethered Pyridine and Thiophene: Synthesis, Crystal Structure Determination and Its Organic Immobilization on Silica for Efficient Solid-Liquid Extraction of Heavy Metals

by Smaail Radi^1,2,*

, Said Tighadouini¹, Maryse Bacquet³, Stephanie Degoutin³, Jean-Philippe Dacquin⁴, Driss Eddike⁵, Monique Tillard⁶

and Yahia N. Mabkhot⁷

¹ Laboratoire de Chimie Appliquée et Environnement (LCAE), Faculté des Sciences, Université Mohamed I, Oujda 60 000, Morocco

² Centre de l’Oriental des Sciences et Technologies de l’Eau (COSTE), Université Med I, Oujda 60 000, Morocco

³ Unité Matériaux et Transformations (UMET) - UMR CNRS 8207 Université Lille 1, 59655 Villeneuve d’Ascq Cedex, France

⁴ Univ. Lille, CNRS, Centrale Lille, ENSCL, Univ. Artois, UMR 8181–UCCS–Unité de Catalyse et Chimie du Solide, F-59000 Lille, France

⁵ Laboratoire de Chimie du Solide Minéral et Analytique, Faculté des Sciences, Université Mohamed I, Oujda 60 000, Morocco

⁶ Institut Charles Gerhardt—AIME, UMR 5253, CC1502, Université de Montpellier, 2 place Eugène Bataillon, 34095 Montpellier Cedex 5, France

⁷ Department of Chemistry, Faculty of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia

Molecules 2016, 21(7), 888; https://doi.org/10.3390/molecules21070888 - 7 Jul 2016

Cited by 14 | Viewed by 6348

Abstract

Molecules bearing β-keto-enol functionality are potential candidates for coordination chemistry. Reported herein is the first synthesis and use of a novel designed ligand based on β-keto-enol group embedded with pyridine and thiophene moieties. The product was prepared in a one-step procedure by mixed [...] Read more.

Molecules bearing β-keto-enol functionality are potential candidates for coordination chemistry. Reported herein is the first synthesis and use of a novel designed ligand based on β-keto-enol group embedded with pyridine and thiophene moieties. The product was prepared in a one-step procedure by mixed Claisen condensation and was characterized by EA, m/z, FT-IR, (¹H, ¹³C) NMR and single-crystal X-ray diffraction analysis. The new structure was grafted onto silica particles to afford a chelating matrix which was well-characterized by EA, FT-IR, solid-state ¹³C-NMR, BET, BJH, SEM and TGA. The newly prepared organic-inorganic material was used as an adsorbent for efficient solid-phase extraction (SPE) of Cu(II), Zn(II), Cd(II) and Pb(II) from aqueous solutions and showed a capture capacity of 104.12 mg·g⁻¹, 98.90 mg·g⁻¹, 72.02 mg·g⁻¹, and 65.54 mg·g⁻¹, respectively. The adsorption capacity was investigated, in a batch method, using time of contact, pH, initial concentration, kinetics (Langmuir and Freundlich models), and thermodynamic parameters (ΔG°, ΔH° and ΔS°) of the system effects. Full article

(This article belongs to the Section Molecular Diversity)

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10 pages, 935 KiB

Open AccessCommunication

Cytotoxic Alkaloids from the Stem of Xylopia laevigata

by Leociley R. A. Menezes¹, Cinara O. D´Sousa Costa², Ana Carolina B. da C. Rodrigues², Felipe R. do E. Santo², Angelita Nepel³, Lívia M. Dutra³, Felipe M. A. Silva⁴, Milena B. P. Soares^2,5, Andersson Barison³, Emmanoel V. Costa^4,* and Daniel P. Bezerra^2,*

¹ Department of Chemistry, Federal University of Sergipe, São Cristóvão 49100-000, Sergipe, Brazil

² Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ), Salvador 40000-000, Bahia, Brazil

³ NMR Center, Federal University of Paraná, Curitiba 80000-000, Paraná, Brazil

⁴ Department of Chemistry, Federal University of Amazonas, Manaus 69000-000, Amazonas, Brazil

⁵ Center of Biotechnology and Cell therapy, Hospital São Rafael, Salvador 40000-000, Bahia, Brazil

Molecules 2016, 21(7), 890; https://doi.org/10.3390/molecules21070890 - 8 Jul 2016

Cited by 35 | Viewed by 7694

Abstract

Xylopia laevigata (Annonaceae), known locally as “meiú” or “pindaíba”, is widely used in folk medicine in Northeastern Brazil. In the present work, we performed phytochemical analyses of the stem of X. laevigata, which led to the isolation of 19 alkaloids: (−)-roemerine, (+)-anonaine, [...] Read more.

Xylopia laevigata (Annonaceae), known locally as “meiú” or “pindaíba”, is widely used in folk medicine in Northeastern Brazil. In the present work, we performed phytochemical analyses of the stem of X. laevigata, which led to the isolation of 19 alkaloids: (−)-roemerine, (+)-anonaine, lanuginosine, (+)-glaucine, (+)-xylopine, oxoglaucine, (+)-norglaucine, asimilobine, (−)-xylopinine, (+)-norpurpureine, (+)-N-methyllaurotetanine, (+)-norpredicentrine, (+)-discretine, (+)-calycinine, (+)-laurotetanine, (+)-reticuline, (−)-corytenchine, (+)-discretamine and (+)-flavinantine. The in vitro cytotoxic activity toward the tumor cell lines B16-F10 (mouse melanoma), HepG2 (human hepatocellular carcinoma), K562 (human chronic myelocytic leukemia) and HL-60 (human promyelocytic leukemia) and non-tumor peripheral blood mononuclear cells (PBMCs) was tested using the Alamar Blue assay. Lanuginosine, (+)-xylopine and (+)-norglaucine had the highest cytotoxic activity. Additionally, the pro-apoptotic effects of lanuginosine and (+)-xylopine were investigated in HepG2 cells using light and fluorescence microscopies and flow cytometry-based assays. Cell morphology consistent with apoptosis and a marked phosphatidylserine externalization were observed in lanuginosine- and (+)-xylopine-treated cells, suggesting induction of apoptotic cell death. In addition, (+)-xylopine treatment caused G₂/M cell cycle arrest in HepG2 cells. These data suggest that X. laevigata is a potential source for cytotoxic alkaloids. Full article

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

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19 pages, 4868 KiB

Open AccessArticle

In Vitro Reversible and Time-Dependent CYP450 Inhibition Profiles of Medicinal Herbal Plant Extracts Newbouldia laevis and Cassia abbreviata: Implications for Herb-Drug Interactions

by Nicholas Ekow Thomford^1,2

, Kevin Dzobo^3,4

, Denis Chopera⁵, Ambroise Wonkam¹, Alfred Maroyi⁶

, Dee Blackhurst⁷

and Collet Dandara^1,*

¹ Division of Human Genetics, Department of Pathology & Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa

² School of Medical Sciences, University of Cape Coast, Cape Coast, PMB, Ghana

³ ICGEB, Cape Town Component, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa

⁴ Division of Medical Biochemistry, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa

⁵ Division of Medical Virology, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa

⁶ Department of Botany, University of Fort Hare, Private Bag X1314, Alice 5700, South Africa

⁷ Division of Chemical Pathology, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa

Molecules 2016, 21(7), 891; https://doi.org/10.3390/molecules21070891 - 7 Jul 2016

Cited by 35 | Viewed by 9073

Abstract

This study evaluated the effects of Newbouldia laevis and Cassia abbreviata extracts on CYP450 enzyme activity. Recombinant CYP450 enzyme and fluorogenic substrates were used for evaluating inhibition, allowing the assessment of herb–drug interactions (HDI). Phytochemical fingerprinting was performed using UPLC-MS. The herbal extracts [...] Read more.

This study evaluated the effects of Newbouldia laevis and Cassia abbreviata extracts on CYP450 enzyme activity. Recombinant CYP450 enzyme and fluorogenic substrates were used for evaluating inhibition, allowing the assessment of herb–drug interactions (HDI). Phytochemical fingerprinting was performed using UPLC-MS. The herbal extracts were risk ranked for HDI based on the IC₅₀ values determined for each CYP enzyme. Newbouldia laevis inhibited CYP1A2, CYP2C9, and CYP2C19 enzyme activities with K_i of 2.84 µg/mL, 1.55 µg/mL, and 1.23 µg/mL, respectively. N. laevis exhibited a TDI (4.17) effect on CYP1A2 but not CYP2C9 and CYP2C19 enzyme activities. Cassia abbreviata inhibited CYP1A2, CYP2C9, and CYP2C19 enzyme activities showing a K_i of 4.86 µg/mL, 5.98 µg/mL, and 1.58 µg/mL, respectively. TDI potency assessment for Cassia abbreviata showed it as a potential TDI candidate (1.64) for CYP1A2 and CYP2C19 (1.72). UPLC-MS analysis showed that Newbouldia laevis and Cassia abbreviata possess polyphenols that likely give them their therapeutic properties; some of them are likely to be responsible for the observed inhibition. The observations made in this study suggest the potential for these herbal compounds to interact, especially when co-administered with other medications metabolized by these CYP450 enzymes. Full article

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

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17 pages, 920 KiB

Open AccessArticle

Biochemical Constituents and in Vitro Antioxidant and Anticholinesterase Potential of Seeds from Native Korean Persimmon Genotypes

by Saqib Bilal¹, Abdul Latif Khan², Muhammad Waqas^1,3, Raheem Shahzad¹, Il-Doo Kim⁴, In-Jung Lee¹ and Dong-Hyun Shin^1,*

¹ School of Applied Biosciences, Kyungpook National University, Daegu 41566, Korea

² UoN Chair of Oman’s Medicinal Plants & Marine Natural Products, University of Nizwa, Nizwa 616, Oman

³ Department of Agriculture, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan

⁴ International Institute of Agriculture Research & Development, Kyungpook National University, Daegu 41566, Korea

Molecules 2016, 21(7), 893; https://doi.org/10.3390/molecules21070893 - 8 Jul 2016

Cited by 25 | Viewed by 6544

Abstract

In the current study, the functional and biochemical potential of the seeds of four persimmon cultivars (PC1, PC2, PC3 and PC4) and their role against oxidative stress and acetylcholinesterase (AChE) inhibition were evaluated. In terms of biochemical compositions, free amino acids, fatty acids [...] Read more.

In the current study, the functional and biochemical potential of the seeds of four persimmon cultivars (PC1, PC2, PC3 and PC4) and their role against oxidative stress and acetylcholinesterase (AChE) inhibition were evaluated. In terms of biochemical compositions, free amino acids, fatty acids and organic acids analysis was performed. The free amino acids ranged from 2617.31 (PC2) to 3773.01 μg∙g⁻¹ dry weight (PC4). Oleic acid and linoleic acid were the principal fatty acids, which were significantly higher in PC4 and PC1, respectively. PC4 presented the highest amount of organic acid content (4212 mg∙kg⁻¹), whereas PC2 presented the lowest (2498 mg∙kg⁻¹). PC2 contained higher total phenolic content and flavonoid content, whereas PC3 had the lowest amount as compared to other cultivars. The in vitro DPPH, ABTS and superoxide anion radicals scavenging activity increased in a dose-dependent manner, whereas PC2 showed significantly higher scavenging activities as compared to PC1, PC2 and PC4 types. In the case of AChE inhibition, PC4 showed a moderate activity (67.34% ± 1.8%). In conclusion, the current findings reveal that the studied persimmon seeds cultivars are a source of bioactive natural antioxidants and AChE inhibitors. Such natural products could be employed in pharmaceutical and food industries, whilst can also be considered for the treatment of neurodegenerative diseases such as Alzheimer’s. Full article

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13 pages, 1879 KiB

Open AccessArticle

Site-Specific, Covalent Immobilization of Dehalogenase ST2570 Catalyzed by Formylglycine-Generating Enzymes and Its Application in Batch and Semi-Continuous Flow Reactors

by Hui Jian, Yingwu Wang^*, Yan Bai, Rong Li and Renjun Gao^*

Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Science, Jilin University, Changchun 130012, China

Molecules 2016, 21(7), 895; https://doi.org/10.3390/molecules21070895 - 11 Jul 2016

Cited by 26 | Viewed by 6791

Abstract

Formylglycine-generating enzymes can selectively recognize and oxidize cysteine residues within the sulfatase sub motif at the terminus of proteins to form aldehyde-bearing formylglycine (FGly) residues, and are normally used in protein labeling. In this study, an aldehyde tag was introduced to proteins using [...] Read more.

Formylglycine-generating enzymes can selectively recognize and oxidize cysteine residues within the sulfatase sub motif at the terminus of proteins to form aldehyde-bearing formylglycine (FGly) residues, and are normally used in protein labeling. In this study, an aldehyde tag was introduced to proteins using formylglycine-generating enzymes encoded by a reconstructed set of the pET28a plasmid system for enzyme immobilization. The haloacid dehalogenase ST2570 from Sulfolobus tokodaii was used as a model enzyme. The C-terminal aldehyde-tagged ST2570 (ST2570CQ) exhibited significant enzymological properties, such as new free aldehyde groups, a high level of protein expression and improved enzyme activity. SBA-15 has widely been used as an immobilization support for its large surface and excellent thermal and chemical stability. It was functionalized with amino groups by aminopropyltriethoxysilane. The C-terminal aldehyde-tagged ST2570 was immobilized to SBA-15 by covalent binding. The site-specific immobilization of ST2570 avoided the chemical denaturation that occurs in general covalent immobilization and resulted in better fastening compared to physical adsorption. The site-specific immobilized ST2570 showed 3-fold higher thermal stability, 1.2-fold higher catalytic ability and improved operational stability than free ST2570. The site-specific immobilized ST2570 retained 60% of its original activity after seven cycles of batch operation, and it was superior to the ST2570 immobilized to SBA-15 by physical adsorption, which loses 40% of its original activity when used for the second time. It is remarkable that the site-specific immobilized ST2570 still retained 100% of its original activity after 10 cycles of reuse in the semi-continuous flow reactor. Overall, these results provide support for the industrial-scale production and application of site-specific, covalently immobilized ST2570. Full article

(This article belongs to the Special Issue Enzyme Immobilization 2016)

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11 pages, 2142 KiB

Open AccessArticle

A High-Throughput Automated Microfluidic Platform for Calcium Imaging of Taste Sensing

by Yi-Hsing Hsiao^1,2, Chia-Hsien Hsu^1,2 and Chihchen Chen^1,3,*

¹ Institute of Nanoengineering and Microsystems, National Tsing Hua University, Hsinchu 30013, Taiwan

² Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli 35053, Taiwan

³ Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan

Molecules 2016, 21(7), 896; https://doi.org/10.3390/molecules21070896 - 8 Jul 2016

Cited by 7 | Viewed by 7431

Abstract

The human enteroendocrine L cell line NCI-H716, expressing taste receptors and taste signaling elements, constitutes a unique model for the studies of cellular responses to glucose, appetite regulation, gastrointestinal motility, and insulin secretion. Targeting these gut taste receptors may provide novel treatments for [...] Read more.

The human enteroendocrine L cell line NCI-H716, expressing taste receptors and taste signaling elements, constitutes a unique model for the studies of cellular responses to glucose, appetite regulation, gastrointestinal motility, and insulin secretion. Targeting these gut taste receptors may provide novel treatments for diabetes and obesity. However, NCI-H716 cells are cultured in suspension and tend to form multicellular aggregates, preventing high-throughput calcium imaging due to interferences caused by laborious immobilization and stimulus delivery procedures. Here, we have developed an automated microfluidic platform that is capable of trapping more than 500 single cells into microwells with a loading efficiency of 77% within two minutes, delivering multiple chemical stimuli and performing calcium imaging with enhanced spatial and temporal resolutions when compared to bath perfusion systems. Results revealed the presence of heterogeneity in cellular responses to the type, concentration, and order of applied sweet and bitter stimuli. Sucralose and denatonium benzoate elicited robust increases in the intracellular Ca²⁺ concentration. However, glucose evoked a rapid elevation of intracellular Ca²⁺ followed by reduced responses to subsequent glucose stimulation. Using Gymnema sylvestre as a blocking agent for the sweet taste receptor confirmed that different taste receptors were utilized for sweet and bitter tastes. This automated microfluidic platform is cost-effective, easy to fabricate and operate, and may be generally applicable for high-throughput and high-content single-cell analysis and drug screening. Full article

(This article belongs to the Special Issue Micro/Nano Fluidics and Bio-MEMS)

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8 pages, 3762 KiB

Open AccessArticle

Auto-Tandem Catalysis in Ionic Liquids: Synthesis of 2-Oxazolidinones by Palladium-Catalyzed Oxidative Carbonylation of Propargylic Amines in EmimEtSO₄

by Raffaella Mancuso^1,*

, Asif Maner¹, Ida Ziccarelli¹, Christian Pomelli², Cinzia Chiappe², Nicola Della Ca’³

, Lucia Veltri¹ and Bartolo Gabriele^1,*

¹ Laboratory of Industrial and Synthetic Organic Chemistry (LISOC), Department of Chemistry and Chemical Technologies, University of Calabria, Via Pietro Bucci 12/C, 87036 Arcavacata di Rende (CS), Italy

² Department of Pharmacy, University of Pisa, Via Bonanno 33, 56126 Pisa, Italy

³ Department of Chemistry, University of Parma, Parco Area delle Scienze 17/A, 43124 Parma, Italy

Molecules 2016, 21(7), 897; https://doi.org/10.3390/molecules21070897 - 8 Jul 2016

Cited by 24 | Viewed by 5577

Abstract

A convenient carbonylative approach to 2-oxazolidinone derivatives carried out using an ionic liquid (1-ethyl-3-methylimidazolium ethyl sulfate, EmimEtSO₄) as the solvent is presented. It is based on the sequential concatenation of two catalytic cycles, both catalyzed by the same metal species (auto-tandem [...] Read more.

A convenient carbonylative approach to 2-oxazolidinone derivatives carried out using an ionic liquid (1-ethyl-3-methylimidazolium ethyl sulfate, EmimEtSO₄) as the solvent is presented. It is based on the sequential concatenation of two catalytic cycles, both catalyzed by the same metal species (auto-tandem catalysis): the first cycle corresponds to the oxidative monoaminocarbonylation of the triple bond of propargylic amines to give the corresponding 2-ynamide intermediates, while the second one involves the cyclocarbonylation of the latter to yield 2-(2-oxooxazolidin-5-ylidene)-acetamides. Reactions are carried out using a simple catalytic system consisting of PdI₂ in conjunction with an excess of KI, and the catalyst/solvent system could be recycled several times without appreciable loss of activity after extraction of the organic product with Et₂O. Full article

(This article belongs to the Special Issue Cascade Catalysis)

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10 pages, 1991 KiB

Open AccessArticle

Protective Effects of Costunolide against Hydrogen Peroxide-Induced Injury in PC12 Cells

by Chong-Un Cheong^1,†, Ching-Sheng Yeh^2,3,4,5,†, Yi-Wen Hsieh⁶, Ying-Ray Lee⁷

, Mei-Ying Lin⁸, Chung-Yi Chen^2,*

and Chien-Hsing Lee^9,*

¹ Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Tainan City 73657, Taiwan

² Department of Nutrition and Health Science, School of Medical and Health Sciences, Fooyin University, Kaohsiung City 83102, Taiwan

³ Bio-Medical Technology Developmental Center, Fooyin University, Kaohsiung City 83102, Taiwan

⁴ Department of Medical Technology, School of Medical and Health Sciences, Fooyin University, Kaohsiung City 83102, Taiwan

⁵ Department of Medical Research, Fooyin University Hospital, Ping-Tung County 92847, Taiwan

⁶ Department of Mackay Memorial Hospital Taitung Branch, Taitung County 95054, Taiwan

⁷ Department of Medical Research, Chiayi Christian Hospital, Chiayi City 60002, Taiwan

⁸ Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung City 80708, Taiwan

⁹ Department of Nursing, Min-Hwei Junior College of Health Care Management, Tainan City 73658, Taiwan

^† These authors contributed equally to this work.

Molecules 2016, 21(7), 898; https://doi.org/10.3390/molecules21070898 - 9 Jul 2016

Cited by 42 | Viewed by 9328

Abstract

Oxidative stress-mediated cellular injury has been considered as a major cause of neurodegenerative diseases including Alzheimer’s and Parkinson’s diseases. The scavenging of reactive oxygen species (ROS) mediated by antioxidants may be a potential strategy for retarding the diseases’ progression. Costunolide (CS) is a [...] Read more.

Oxidative stress-mediated cellular injury has been considered as a major cause of neurodegenerative diseases including Alzheimer’s and Parkinson’s diseases. The scavenging of reactive oxygen species (ROS) mediated by antioxidants may be a potential strategy for retarding the diseases’ progression. Costunolide (CS) is a well-known sesquiterpene lactone, used as a popular herbal remedy, which possesses anti-inflammatory and antioxidant activity. This study aimed to investigate the protective role of CS against the cytotoxicity induced by hydrogen peroxide (H₂O₂) and to elucidate potential protective mechanisms in PC12 cells. The results showed that the treatment of PC12 cells with CS prior to H₂O₂ exposure effectively increased the cell viability. Furthermore, it decreased the intracellular ROS, stabilized the mitochondria membrane potential (MMP), and reduced apoptosis-related protein such as caspase 3. In addition, CS treatment attenuated the cell injury by H₂O₂ through the inhibition of phosphorylation of p38 and the extracellular signal-regulated kinase (ERK). These results demonstrated that CS is promising as a potential therapeutic candidate for neurodegenerative diseases resulting from oxidative damage and further research on this topic should be encouraged. Full article

(This article belongs to the Special Issue Potential Neuromodulatory Profile of Phytocompounds in Brain Disorders)

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15 pages, 6165 KiB

Open AccessArticle

Gallic Acid Promotes Wound Healing in Normal and Hyperglucidic Conditions

by Dong Joo Yang^1,2,†, Sang Hyun Moh^3,†, Dong Hwee Son^1,4, Seunghoon You¹, Ann W. Kinyua^1,2, Chang Mann Ko¹, Miyoung Song³, Jinhee Yeo⁵, Yun-Hee Choi^3,* and Ki Woo Kim^1,2,*

¹ Department of Pharmacology, Wonju College of Medicine, Yonsei University, Wonju 26426, Korea

² Department of Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju 26426, Korea

³ Anti-Aging Research Institute of BIO-FD & C Co. Ltd., Incheon 21990, Korea

⁴ Department of Wellness & Healthy Aging, Wonju College of Medicine, Yonsei University, Wonju 26426, Korea

⁵ Jeongseon Agricultural Extension Center, Jeongseon 26103, Korea

^† These authors contributed equally to this work.

Molecules 2016, 21(7), 899; https://doi.org/10.3390/molecules21070899 - 8 Jul 2016

Cited by 157 | Viewed by 11276

Abstract

Skin is the outermost layer of the human body that is constantly exposed to environmental stressors, such as UV radiation and toxic chemicals, and is susceptible to mechanical wounding and injury. The ability of the skin to repair injuries is paramount for survival [...] Read more.

Skin is the outermost layer of the human body that is constantly exposed to environmental stressors, such as UV radiation and toxic chemicals, and is susceptible to mechanical wounding and injury. The ability of the skin to repair injuries is paramount for survival and it is disrupted in a spectrum of disorders leading to skin pathologies. Diabetic patients often suffer from chronic, impaired wound healing, which facilitate bacterial infections and necessitate amputation. Here, we studied the effects of gallic acid (GA, 3,4,5-trihydroxybenzoic acid; a plant-derived polyphenolic compound) on would healing in normal and hyperglucidic conditions, to mimic diabetes, in human keratinocytes and fibroblasts. Our study reveals that GA is a potential antioxidant that directly upregulates the expression of antioxidant genes. In addition, GA accelerated cell migration of keratinocytes and fibroblasts in both normal and hyperglucidic conditions. Further, GA treatment activated factors known to be hallmarks of wound healing, such as focal adhesion kinases (FAK), c-Jun N-terminal kinases (JNK), and extracellular signal-regulated kinases (Erk), underpinning the beneficial role of GA in wound repair. Therefore, our results demonstrate that GA might be a viable wound healing agent and a potential intervention to treat wounds resulting from metabolic complications. Full article

(This article belongs to the Special Issue New Frontiers on the Metabolism, Bioavailability and Health Effects of Phenolic Compounds)

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10 pages, 1961 KiB

Open AccessArticle

In Situ Enzymatically Generated Photoswitchable Oxidase Mimetics and Their Application for Colorimetric Detection of Glucose Oxidase

by Gen-Xia Cao, Xiu-Ming Wu, Yu-Ming Dong, Zai-Jun Li and Guang-Li Wang^*

The Key Laboratory of Food Colloids and Biotechnology, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, China

Molecules 2016, 21(7), 902; https://doi.org/10.3390/molecules21070902 - 9 Jul 2016

Cited by 8 | Viewed by 7019

Abstract

In this study, a simple and amplified colorimetric assay is developed for the detection of the enzymatic activity of glucose oxidase (GOx) based on in situ formation of a photoswitchable oxidase mimetic of PO₄³⁻-capped CdS quantum dots (QDs). GOx catalyzes [...] Read more.

In this study, a simple and amplified colorimetric assay is developed for the detection of the enzymatic activity of glucose oxidase (GOx) based on in situ formation of a photoswitchable oxidase mimetic of PO₄³⁻-capped CdS quantum dots (QDs). GOx catalyzes the oxidation of 1-thio-β-d-glucose to give 1-thio-β-d-gluconic acid which spontaneously hydrolyzes to β-d-gluconic acid and H₂S; the generated H₂S instantly reacts with Cd²⁺ in the presence of Na₃PO₄ to give PO₄³⁻-stabilized CdS QDs in situ. Under visible-light (λ ≥ 400 nm) stimulation, the PO₄³⁻-capped CdS QDs are a new style of oxidase mimic derived by producing some active species, such as h⁺, ^•OH, O₂^•− and a little H₂O₂, which can oxidize the typical substrate (3,3,5,5-tetramethylbenzydine (TMB)) with a color change. Based on the GOx-triggered growth of the oxidase mimetics of PO₄³⁻-capped CdS QDs in situ, we developed a simple and amplified colorimetric assay to probe the enzymatic activity of GOx. The proposed method allowed the detection of the enzymatic activity of GOx over the range from 25 μg/L to 50 mg/L with a low detection limit of 6.6 μg/L. We believe the PO₄³⁻-capped CdS QDs generated in situ with photo-stimulated enzyme-mimicking activity may find wide potential applications in biosensors. Full article

(This article belongs to the Special Issue Nanozymes and Beyond)

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12 pages, 1370 KiB

Open AccessArticle

Efficient MW-Assisted Synthesis, Spectroscopic Characterization, X-ray and Antioxidant Properties of Indazole Derivatives

by Efrain Polo¹

, Jorge Trilleras²

, Juan Ramos², Antonio Galdámez³

, Jairo Quiroga⁴

and Margarita Gutierrez^1,*

¹ Organic Synthesis Laboratory and Biological Activity (LSO-Act-Bio), Institute of Chemistry of Natural Resources, Universidad de Talca, Casilla 747, Talca 3460000, Chile

² Grupo/Semillero de Investigación en Compuestos Heterocíclicos, Programa de Química, Facultad de Ciencias Básicas, Universidad del Atlántico, Km 7 Antigua vía Puerto Colombia, Barranquilla 081007, Atlántico, Colombia

³ Solid State Chemistry Laboratory, Science Faculty, University of Chile, Santiago, 7800003, Chile

⁴ Heterocyclic Compounds Research Group, Department of Chemistry, Universidad del Valle, Cali A.A. 25360, Colombia

Molecules 2016, 21(7), 903; https://doi.org/10.3390/molecules21070903 - 9 Jul 2016

Cited by 14 | Viewed by 6650

Abstract

A small series of tetrahydroindazoles was prepared, starting from 2-acetylcyclohexanone and different hydrazines using reflux and a focused microwave reactor. Microwave irradiation (MW) favored the formation of the desired products with improved yields and shortened reaction times. This is a simple and green [...] Read more.

A small series of tetrahydroindazoles was prepared, starting from 2-acetylcyclohexanone and different hydrazines using reflux and a focused microwave reactor. Microwave irradiation (MW) favored the formation of the desired products with improved yields and shortened reaction times. This is a simple and green method for the synthesis of substituted tetrahydroindazole derivatives. The in vitro antioxidant activity was evaluated using the DPPH and ABTS methods. In these assays, 2-(4-fluorophenyl)-3-methyl-4,5,6,7-tetrahydro-2H-indazole (3f) showed moderate DPPH decoloring activity, while 3-methyl-4,5,6,7-tetrahydro-1H-indazole (3a), 3-methyl-2-phenyl-4,5,6,7-tetrahydro-2H-indazole (3b) and 2-(4-fluorophenyl)-3-methyl-4,5,6,7-tetrahydro-2H-indazole (3f) were the most active in the ABTS assay. All compounds were well characterized by IR, ¹H-, ¹³C-NMR and GC-MS spectroscopy and physical data, while the structure of 4-(3-methyl-4,5,6,7-tetrahydro-2H-indazol-2-yl)benzoic acid (3e) was also determined by single crystal X-ray analysis. Full article

(This article belongs to the Section Green Chemistry)

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10 pages, 2895 KiB

Open AccessArticle

Fluorinated Polyurethanes, Synthesis and Properties

by Olga Smirnova, Alexey Glazkov, Alexander Yarosh and Alexey Sakharov^*

N.D. Zelinsky Institute of Organic Chemistry of Russian Academy of Sciences, 47 Leninsky Avenue, Moscow 119991, Russian

Molecules 2016, 21(7), 904; https://doi.org/10.3390/molecules21070904 - 12 Jul 2016

Cited by 18 | Viewed by 7165

Abstract

Fluorinated polyurethanes with a glass transition temperature as low as −139 °C and a decomposition onset temperature of 247–330 °C were prepared by a reaction of fluorinated alcohols with aromatic and cycloaliphatic diisocyanates in solution or melt. Full article

(This article belongs to the Special Issue Fluorine Chemistry 2016)

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10 pages, 1795 KiB

Open AccessArticle

Enzymatic Hydrolytic Resolution of Racemic Ibuprofen Ethyl Ester Using an Ionic Liquid as Cosolvent

by Tao Wei^1,2, Kunpeng Yang^1,2, Bing Bai¹, Jie Zang¹, Xuan Yu¹ and Duobin Mao^1,2,*

¹ School of Food and Biological Engineering, Zhengzhou University of Light Industry, 5 Dongfeng Rd., Zhengzhou 450002, China

² Collaborative Innovation Center of Food Production and Safety, 136 Science Avenue, Zhengzhou 450002, China

Molecules 2016, 21(7), 905; https://doi.org/10.3390/molecules21070905 - 13 Jul 2016

Cited by 12 | Viewed by 5868

Abstract

The aim of this study was to develop an ionic liquid (IL) system for the enzymatic resolution of racemic ibuprofen ethyl ester to produce (S)-ibuprofen. Nineteen ILs were selected for use in buffer systems to investigate the effects of ILs as [...] Read more.

The aim of this study was to develop an ionic liquid (IL) system for the enzymatic resolution of racemic ibuprofen ethyl ester to produce (S)-ibuprofen. Nineteen ILs were selected for use in buffer systems to investigate the effects of ILs as cosolvents for the production of (S)-ibuprofen using thermostable esterase (EST10) from Thermotoga maritima. Analysis of the catalytic efficiency and conformation of EST10 showed that [OmPy][BF₄] was the best medium for the EST10-catalyzed production of (S)-ibuprofen. The maximum degree of conversion degree (47.4%), enantiomeric excess of (S)-ibuprofen (96.6%) and enantiomeric ratio of EST10 (177.0) were achieved with an EST10 concentration of 15 mg/mL, racemic ibuprofen ethyl ester concentration of 150 mM, at 75 °C , with a reaction time of 10 h. The reaction time needed to achieve the highest yield of (S)-ibuprofen was decreased from 24 h to 10 h. These results are relevant to the proposed application of ILs as solvents for the EST10-catalyzed production of (S)-ibuprofen. Full article

(This article belongs to the Special Issue Recent Developments in Using Biocatalysts and Whole Cells for Organic Synthesis)

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22 pages, 5772 KiB

Open AccessArticle

The Interference of Selected Cytotoxic Alkaloids with the Cytoskeleton: An Insight into Their Modes of Action

by Xiaojuan Wang^*

, Mine Tanaka

, Sonja Krstin, Herbenya Silva Peixoto

and Michael Wink

Department of Biology, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, INF 364, D-69120 Heidelberg, Germany

Molecules 2016, 21(7), 906; https://doi.org/10.3390/molecules21070906 - 12 Jul 2016

Cited by 31 | Viewed by 8328

Abstract

Alkaloids, the largest group among the nitrogen-containing secondary metabolites of plants, usually interact with several molecular targets. In this study, we provide evidence that six cytotoxic alkaloids (sanguinarine, chelerythrine, chelidonine, noscapine, protopine, homoharringtonine), which are known to affect neuroreceptors, protein biosynthesis and nucleic [...] Read more.

Alkaloids, the largest group among the nitrogen-containing secondary metabolites of plants, usually interact with several molecular targets. In this study, we provide evidence that six cytotoxic alkaloids (sanguinarine, chelerythrine, chelidonine, noscapine, protopine, homoharringtonine), which are known to affect neuroreceptors, protein biosynthesis and nucleic acids, also interact with the cellular cytoskeleton, such as microtubules and actin filaments, as well. Sanguinarine, chelerythrine and chelidonine depolymerized the microtubule network in living cancer cells (Hela cells and human osteosarcoma U2OS cells) and inhibited tubulin polymerization in vitro with IC₅₀ values of 48.41 ± 3.73, 206.39 ± 4.20 and 34.51 ± 9.47 μM, respectively. However, sanguinarine and chelerythrine did not arrest the cell cycle while 2.5 μM chelidonine arrested the cell cycle in the G₂/M phase with 88.27% ± 0.99% of the cells in this phase. Noscapine and protopine apparently affected microtubule structures in living cells without affecting tubulin polymerization in vitro, which led to cell cycle arrest in the G2/M phase, promoting this cell population to 73.42% ± 8.31% and 54.35% ± 11.26% at a concentration of 80 μM and 250.9 μM, respectively. Homoharringtonine did not show any effects on microtubules and cell cycle, while the known microtubule-stabilizing agent paclitaxel was found to inhibit tubulin polymerization in the presence of MAPs in vitro with an IC₅₀ value of 38.19 ± 3.33 μM. Concerning actin filaments, sanguinarine, chelerythrine and chelidonine exhibited a certain effect on the cellular actin filament network by reducing the mass of actin filaments. The interactions of these cytotoxic alkaloids with microtubules and actin filaments present new insights into their molecular modes of action. Full article

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

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14 pages, 1848 KiB

Open AccessArticle

Ellagitannins from Raspberry (Rubus idaeus L.) Fruit as Natural Inhibitors of Geotrichum candidum

by Elżbieta Klewicka^1,*, Michał Sójka^2,*, Robert Klewicki²

, Krzysztof Kołodziejczyk², Lidia Lipińska¹ and Adriana Nowak¹

¹ Institute of Fermentation Technology and Microbiology, Lodz University of Technology, Wolczanska 171/173, Lodz 90-924, Poland

² Institute of Food Technology and Analysis, Lodz University of Technology, Stefanowskiego 4/10, Lodz 90-924, Poland

Molecules 2016, 21(7), 908; https://doi.org/10.3390/molecules21070908 - 13 Jul 2016

Cited by 42 | Viewed by 8610

Abstract

The paper presents the chemical characteristics of ellagitannins isolated from raspberry (Rubus idaeus L.) fruit and their in vitro and in situ antifungal activity against Geotrichum candidum ŁOCK 0511. The study investigated a complex preparation containing various raspberry ellagitannins at a concentration [...] Read more.

The paper presents the chemical characteristics of ellagitannins isolated from raspberry (Rubus idaeus L.) fruit and their in vitro and in situ antifungal activity against Geotrichum candidum ŁOCK 0511. The study investigated a complex preparation containing various raspberry ellagitannins at a concentration of 86% w/w, as well as pure lambertianin C and sanguiin H-6. The ellagitannin preparation was obtained by extracting raspberry press cake and purifying the extract using Amberlite XAD resin, while individual compounds were isolated by means of preparative HPLC. The complex preparation was analyzed for the content of ellagitannins, anthocyanins, and flavan-3-ols using HPLC and LC-MS. The antifungal activity of the complex ellagitannin preparation and the isolated ellagitannins was determined for the strain Geotrichum candidum. The MIC and MFC values (10.0 mg/mL and 30.0 mg/mL, respectively) were found to be the same for lambertianin C, sanguiin H-6, and the complex ellagitannin preparation. The fungistatic activity of the studied ellagitannin preparation at a concentration of 10 mg/mL, as determined by the poisoned medium method, was 65.2% following 6 day incubation of Geotrichum candidum, with the linear growth rate of only 16.2 mm/day. The corresponding parameters for the control sample were 0% and 56 mm/day, respectively. The study demonstrated both in vitro and in situ antifungal activity of raspberry ellagitannins against Geotrichum candidum. Full article

(This article belongs to the Collection Bioactive Compounds)

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12 pages, 4166 KiB

Open AccessArticle

New Potential Antimalarial Agents: Design, Synthesis and Biological Evaluation of Some Novel Quinoline Derivatives as Antimalarial Agents

by Ibrahim Ali M. Radini¹, Tarek M. Y. Elsheikh^2,3, Emad M. El-Telbani^1,4 and Rizk E. Khidre^1,4,*

¹ Chemistry Department, Faculty of Science, Jazan University, Jazan 2097, Saudi Arabia

² Biology Department, Faculty of Science, Jazan University, Jazan 2097, Saudi Arabia

³ Department of Zoology, Faculty of Science, Al-Azhar University, Cairo 11675, Egypt

⁴ Chemical Industries Division, National Research Centre, Dokki 12622, Giza, Egypt

Molecules 2016, 21(7), 909; https://doi.org/10.3390/molecules21070909 - 14 Jul 2016

Cited by 60 | Viewed by 8753

Abstract

A novel series of dihydropyrimidines (DHPMs) 4a–j; 2-oxopyran-3-carboxylate 7a,b; 1-amino-1,2-dihydropyridine-3-carboxylate 8; and 1,3,4-oxadiazole derivatives 12 with quinolinyl residues have been synthesized in fairly good yields. The structure of the newly synthesized compounds was elucidated on the basis of [...] Read more.

A novel series of dihydropyrimidines (DHPMs) 4a–j; 2-oxopyran-3-carboxylate 7a,b; 1-amino-1,2-dihydropyridine-3-carboxylate 8; and 1,3,4-oxadiazole derivatives 12 with quinolinyl residues have been synthesized in fairly good yields. The structure of the newly synthesized compounds was elucidated on the basis of analytical and spectral analyses. In vitro antimalarial evaluation of the synthesized quinoline derivatives against Plasmodium falciparum revealed them to possess moderate to high antimalarial activities, with IC₅₀ values ranging from 0.014–5.87 μg/mL. Compounds 4b,g,i and 12 showed excellent antimalarial activity against to Plasmodium falciparum compared with the antimalarial agent chloroquine (CQ). Full article

(This article belongs to the Special Issue Drug Design and Discovery: Principles and Applications)

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15 pages, 1561 KiB

Open AccessArticle

Characterization and Analysis of 2-(2-Phenylethyl)-chromone Derivatives from Agarwood (Aquilaria crassna) by Artificial Holing for Different Times

by Jin Ling Yang

, Wen Hua Dong, Fan Dong Kong, Ge Liao, Jun Wang, Wei Li, Wen Li Mei^* and Hao Fu Dai^*

Hainan Key Laboratory for Research and Development of Natural Products from Li Folk Medicine, Key Laboratory of Tropical Crop Biotechnology, Ministry of Agriculture, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, Hainan, China

Molecules 2016, 21(7), 911; https://doi.org/10.3390/molecules21070911 - 13 Jul 2016

Cited by 39 | Viewed by 6937

Abstract

A total of fifty-six chromones, including seven 5,6,7,8-tetrahydro-2-(2-phenylethyl)-chromones (THPECs), five 5,6-epoxy-2-(2-phenylethyl)chromones (EPECs), seven 5,6:7,8-diepoxy-2-(2-phenylethyl)chromones (DEPECs) and thirty-seven 2-(2-phenylethyl)chromones of the flidersia type (FTPECs), were characterized by HPLC/DAD/ESI/MS/MS in three agarwood samples (from Aquilaria crassna) induced by artificial holing with different holing times. [...] Read more.

A total of fifty-six chromones, including seven 5,6,7,8-tetrahydro-2-(2-phenylethyl)-chromones (THPECs), five 5,6-epoxy-2-(2-phenylethyl)chromones (EPECs), seven 5,6:7,8-diepoxy-2-(2-phenylethyl)chromones (DEPECs) and thirty-seven 2-(2-phenylethyl)chromones of the flidersia type (FTPECs), were characterized by HPLC/DAD/ESI/MS/MS in three agarwood samples (from Aquilaria crassna) induced by artificial holing with different holing times. The characteristic fragmentation behavior of DEPECs and EPECs, and the methods to distinguish these four types of chromones by MS analysis were described for the first time. In addition, it was found that the relative contents of DEPECs and EPECs were down-regulated, while the relative contents of THPECs and FTPECs were up-regulated for the samples from two, four and five years of the agarwood formation time. However, the relative contents of six most widespread and abundant FTPECs presented roughly upward based on the formation time. These results could be referenced to distinguish different agarwood samples collected from different formation time. Full article

(This article belongs to the Collection Bioactive Compounds)

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13 pages, 2213 KiB

Open AccessArticle

Differential Effects of Viscum album Preparations on the Maturation and Activation of Human Dendritic Cells and CD4⁺ T Cell Responses

by Chaitrali Saha^1,2,3, Mrinmoy Das^1,3,4, Emmanuel Stephen-Victor^1,3,4, Alain Friboulet², Jagadeesh Bayry^1,3,4,5,*

and Srini V. Kaveri^1,3,4,5,*

¹ Institut National de la Santé et de la Recherche Médicale Unité 1138, Centre de Recherche des Cordeliers, 15 rue de l’Ecole de Médicine, Paris F-75006, France

² Université de Technologie de Compiègne, UMR CNRS 6022, Compiègne F-60205, France

³ Centre de Recherche des Cordeliers, Immunopathologie et Immuno-Intervention Thérapeutique, Paris F-75006, France

⁴ Sorbonne Universités, UPMC Univ Paris 06, UMR S 1138, Paris F-75006, France

⁵ Université Paris Descartes, Sorbonne Paris Cité, UMR S 1138, Paris F-75006, France

Molecules 2016, 21(7), 912; https://doi.org/10.3390/molecules21070912 - 14 Jul 2016

Cited by 20 | Viewed by 7152 | Correction

Abstract

Extracts of Viscum album (VA); a semi-parasitic plant, are frequently used in the complementary therapy of cancer and other immunological disorders. Various reports show that VA modulates immune system and exerts immune-adjuvant activities that might influence tumor regression. Currently, several therapeutic preparations of [...] Read more.

Extracts of Viscum album (VA); a semi-parasitic plant, are frequently used in the complementary therapy of cancer and other immunological disorders. Various reports show that VA modulates immune system and exerts immune-adjuvant activities that might influence tumor regression. Currently, several therapeutic preparations of VA are available and hence an insight into the mechanisms of action of different VA preparations is necessary. In the present study, we performed a comparative study of five different preparations of VA on maturation and activation of human dendritic cells (DCs) and ensuing CD4⁺ T cell responses. Monocyte-derived human DCs were treated with VA Qu Spez, VA Qu Frf, VA M Spez, VA P and VA A. Among the five VA preparations tested VA Qu Spez, a fermented extract with a high level of lectins, significantly induced DC maturation markers CD83, CD40, HLA-DR and CD86, and secretion of pro-inflammatory cytokines such as IL-6, IL-8, IL-12 and TNF-α. Furthermore, analysis of T cell cytokines in DC-T cell co-culture revealed that VA Qu Spez significantly stimulated IFN-γ secretion without modulating regulatory T cells and other CD4⁺ T cytokines IL-4, IL-13 and IL-17A. Our study thus delineates differential effects of VA preparations on DC maturation; function and T cell responses. Full article

(This article belongs to the Special Issue Natural Products and Inflammation)

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15 pages, 2610 KiB

Open AccessArticle

Simultaneous Determination of Eight Alkaloids in Rat Plasma by UHPLC-MS/MS after Oral Administration of Coptis deltoidea C. Y. Cheng et Hsiao and Coptis chinensis Franch

by Lu Liu¹, Zhi-Bin Wang², Yang Song³, Jing Yang⁴, Li-Jun Wu¹, Bing-You Yang², Qiu-Hong Wang², Li-Qian Wang¹, Ru-Xuan Wang¹ and Chun-Juan Yang^1,*

¹ Department of Pharmaceutical Analysis and Analytical Chemistry, College of Pharmacy, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China

² Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, 24 Heping Road, Xiangfang District, Harbin 150040, China

³ School of Pharmacy, China Medical University, Shenyang 110001, China

⁴ Analytical Department, Johnson & Johnson, 199 Grandview Road, Skillman, NJ 08558, USA

Molecules 2016, 21(7), 913; https://doi.org/10.3390/molecules21070913 - 14 Jul 2016

Cited by 25 | Viewed by 6543

Abstract

A ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) method was successfully developed and validated for the identification and determination of eight alkaloids: tetrahydropalmatine (A); palmatine (B); magnoflorine (C); columbamine (D); berberine (E [...] Read more.

A ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) method was successfully developed and validated for the identification and determination of eight alkaloids: tetrahydropalmatine (A); palmatine (B); magnoflorine (C); columbamine (D); berberine (E); worenine (F); berberrubine (G) and coptisine (H) in rat plasma, which are the active components in Coptis deltoidea C. Y. cheng et Hsiao (CCY) and Coptis chinensis Franch (CF). The chromatographic separation of analytes was successfully achieved on an Agilent SB-C₁₈ column (1.8 µm, 150 mm × 2.1 mm) using a programme with a mobile phase consisting of acetonitrile and water containing 0.3% acetic acid at a flow rate of 0.25 mL/min. The analytes were detected with a triple quadrupole tandem MS in multiple reaction monitoring (MRM) mode and an electrospray ionization (ESI) source in positive mode. The validated method showed good linearity over a wide concentration range (r² > 0.991), and lower limits of quantification (LLOQ) less than 1.1 ng/mL for all analytes, and matrix effects ranged from 85.2% to 106.8%. The mean extraction recoveries were no less than 86.4%, and the precision and accuracy were within the acceptable limits. All analytes were proven to be stable during sample storage and analysis procedures. The method validation results demonstrated that the proposed method was sensitive, specific, and reliable, which could lay a foundation for the pharmacokinetic study of eight analytes after oral administration of CCY and CF in subsequent studies. Full article

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13 pages, 1416 KiB

Open AccessArticle

Nobiletin Induces Protective Autophagy Accompanied by ER-Stress Mediated Apoptosis in Human Gastric Cancer SNU-16 Cells

by Jeong Yong Moon¹

and Somi Kim Cho^1,2,*

¹ Subtropical Horticulture Research Institute, Jeju National University, Jeju 63243, Korea

² Faculty of Biotechnology, College of Applied Life Sciences, SARI, Jeju National University, Jeju 63243, Korea

Molecules 2016, 21(7), 914; https://doi.org/10.3390/molecules21070914 - 14 Jul 2016

Cited by 63 | Viewed by 8954

Abstract

Nobiletin, a major component of citrus fruits, is a polymethoxyflavone derivative that exhibits anticancer activity against several forms of cancer, including SNU-16 human gastric cancer cells. To explore the nobiletin-induced cell death mechanism, we examined the changes in protein expression caused by nobiletin [...] Read more.

Nobiletin, a major component of citrus fruits, is a polymethoxyflavone derivative that exhibits anticancer activity against several forms of cancer, including SNU-16 human gastric cancer cells. To explore the nobiletin-induced cell death mechanism, we examined the changes in protein expression caused by nobiletin in human gastric cancer SNU-16 cells by means of two-dimensional gel electrophoresis (2-DGE), followed by peptide mass fingerprinting (PMF) analysis. Seventeen of 20 selected protein spots were successfully identified, including nine upregulated and eight downregulated proteins. In nobiletin-treated SNU-16 cells the glucose-regulated protein 78 kDa (GRP78) mRNA level was induced most significantly among six proteins related to cell survival and death. Western blot analysis was used to confirm the expression of GRP78 protein. We detected increases in the levels of the ER-stress related proteins inositol requiring enzyme 1 alpha (IRE1-α), activating transcription factor 4 (ATF-4), and C/EBP homology protein (CHOP), as well as GRP78, in response to nobiletin in SNU-16 cells. Furthermore, the ER stress-mediated apoptotic protein caspase-4 was proteolytically activated by nobiletin. Pretreatment with chloroquine, an autophagy inhibitor, strongly augmented apoptosis in SNU-16 cells, as evidenced by decreased cell viability, an increased number of sub-G1 phase cells and increased levels of cleaved PARP. Our results suggest that nobiletin-induced apoptosis in SNU-16 cells is mediated by pathways involving intracellular ER stress-mediated protective autophagy. Thus, the combination of nobiletin and an autophagy inhibitor could be a promising treatment for gastric cancer patients. Full article

(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)

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14 pages, 3577 KiB

Open AccessArticle

Synthesis and Characterization of Magnetic Molecularly Imprinted Polymer for the Enrichment of Ofloxacin Enantiomers in Fish Samples

by Yan-Fei Wang, Huo-Xi Jin, Yang-Guang Wang^*, Li-Ye Yang, Xiao-Kun OuYang^* and Wei-Jian Wu

School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China

Molecules 2016, 21(7), 915; https://doi.org/10.3390/molecules21070915 - 14 Jul 2016

Cited by 30 | Viewed by 6713

Abstract

A new method for the isolation and enrichment of ofloxacin enantiomers from fish samples was developed using magnetic molecularly imprinted polymers (MMIPs). These polymers can be easily collected and rapidly separated using an external magnetic field, and also exhibit a high specific recognition [...] Read more.

A new method for the isolation and enrichment of ofloxacin enantiomers from fish samples was developed using magnetic molecularly imprinted polymers (MMIPs). These polymers can be easily collected and rapidly separated using an external magnetic field, and also exhibit a high specific recognition for ofloxacin enantiomers. The preparation of amino-functionalized MMIPs was carried out via suspension polymerization and a ring-opening reaction using rac-ofloxacin as a template, ethylenediamine as an active group, glycidyl methacrylate and methyl methacrylate as functional monomers, divinylbenzene as a cross-linker, and Fe₃O₄ nanoparticles as magnetic cores. The characteristics of the MMIPs were assessed using transmission electron microscopy (TEM), X-ray powder diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and vibrating sample magnetometer (VSM) measurements. Furthermore, the adsorption properties were determined using Langmuir and Freundlich isotherm models. The conditions for use of these MMIPs as magnetic solid-phase extraction (MSPE) sorbents, including pH, adsorption time, desorption time, and eluent, were investigated in detail. An extraction method using MMIPs coupled with high performance liquid chromatography (HPLC) was developed for the determination of ofloxacin enantiomers in fish samples. The limits of quantitation (LOQ) for the developed method were 0.059 and 0.067 μg∙mL⁻¹ for levofloxacin and dextrofloxacin, respectively. The recovery of ofloxacin enantiomers ranged from 79.2% ± 5.6% to 84.4% ± 4.6% and ofloxacin enantiomers had good linear relationships within the concentration range of 0.25–5.0 μg∙mL⁻¹ (R² > 0.999). The obtained results demonstrate that MSPE-HPLC is a promising approach for preconcentration, purification, and simultaneous separation of ofloxacin enantiomers in biomatrix samples. Full article

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

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19 pages, 2236 KiB

Open AccessArticle

Synthesis, Characterization and Anti-Cancer Activity of Hydrazide Derivatives Incorporating a Quinoline Moiety

by Murat Bingul^1,2, Owen Tan², Christopher R. Gardner^1,2, Selina K. Sutton², Greg M. Arndt^2,3, Glenn M. Marshall^2,4, Belamy B. Cheung^2,*, Naresh Kumar^1,* and David StC. Black^1,*

¹ School of Chemistry, The University of New South Wales Australia, Sydney, NSW 2052, Australia

² Children’s Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, The University of New South Wales Australia, Sydney, NSW 2031, Australia

³ ACRF Drug Discovery Centre for Childhood Cancer, Children’s Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, The University of New South Wales Australia, Sydney, NSW 2052, Australia

⁴ Kids Cancer Centre, Sydney Children’s Hospital, Randwick, NSW 2031, Australia

Molecules 2016, 21(7), 916; https://doi.org/10.3390/molecules21070916 - 14 Jul 2016

Cited by 73 | Viewed by 14708

Abstract

Identification of the novel (E)-N′-((2-chloro-7-methoxyquinolin-3-yl)methylene)-3-(phenylthio)propanehydrazide scaffold 18 has led to the development of a new series of biologically active hydrazide compounds. The parent compound 18 and new quinoline derivatives 19–26 were prepared from the corresponding quinoline hydrazones [...] Read more.

Identification of the novel (E)-N′-((2-chloro-7-methoxyquinolin-3-yl)methylene)-3-(phenylthio)propanehydrazide scaffold 18 has led to the development of a new series of biologically active hydrazide compounds. The parent compound 18 and new quinoline derivatives 19–26 were prepared from the corresponding quinoline hydrazones and substituted carboxylic acids using EDC-mediated peptide coupling reactions. Further modification of the parent compound 18 was achieved by replacement of the quinoline moiety with other aromatic systems. All the newly synthesized compounds were evaluated for their anti-cancer activity against the SH-SY5Y and Kelly neuroblastoma cell lines, as well as the MDA-MB-231 and MCF-7 breast adenocarcinoma cell lines. Analogues 19 and 22 significantly reduced the cell viability of neuroblastoma cancer cells with micromolar potency and significant selectivity over normal cells. The quinoline hydrazide 22 also induced G₁ cell cycle arrest, as well as upregulation of the p27^kip1 cell cycle regulating protein. 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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9 pages, 4271 KiB

Open AccessArticle

In Situ Investigation of a Self-Accelerated Cocrystal Formation by Grinding Pyrazinamide with Oxalic Acid

by Hannes Kulla^1,2, Sebastian Greiser¹, Sigrid Benemann¹, Klaus Rademann² and Franziska Emmerling^1,*

¹ Federal Institute for Materials Research and Testing (BAM), Richard-Willstaetter-Str. 11, 12489 Berlin, Germany

² Department of Chemistry, Humboldt-Universität zu Berlin, Brook-Taylor-Str. 2, 12489 Berlin, Germany

Molecules 2016, 21(7), 917; https://doi.org/10.3390/molecules21070917 - 14 Jul 2016

Cited by 40 | Viewed by 8508

Abstract

A new cocrystal of pyrazinamide with oxalic acid was prepared mechanochemically and characterized by PXRD, Raman spectroscopy, solid-state NMR spectroscopy, DTA-TG, and SEM. Based on powder X-ray diffraction data the structure was solved. The formation pathway of the reaction was studied in situ [...] Read more.

A new cocrystal of pyrazinamide with oxalic acid was prepared mechanochemically and characterized by PXRD, Raman spectroscopy, solid-state NMR spectroscopy, DTA-TG, and SEM. Based on powder X-ray diffraction data the structure was solved. The formation pathway of the reaction was studied in situ using combined synchrotron PXRD and Raman spectroscopy. Using oxalic acid dihydrate the initially neat grinding turned into a rapid self-accelerated liquid-assisted grinding process by the release of crystallization water. Under these conditions, the cocrystal was formed directly within two minutes. Full article

(This article belongs to the Special Issue Mechanochemistry)

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23 pages, 1744 KiB

Open AccessArticle

Exploring Flow Procedures for Diazonium Formation

by Te Hu, Ian R. Baxendale^*

and Marcus Baumann

Department of Chemistry, University of Durham, South Road, Durham DH1 3LE, UK

Molecules 2016, 21(7), 918; https://doi.org/10.3390/molecules21070918 - 14 Jul 2016

Cited by 33 | Viewed by 11946

Abstract

The synthesis of diazonium salts is historically an important transformation extensively utilized in dye manufacture. However the highly reactive nature of the diazonium functionality has additionally led to the development of many new reactions including several carbon-carbon bond forming processes. It is therefore [...] Read more.

The synthesis of diazonium salts is historically an important transformation extensively utilized in dye manufacture. However the highly reactive nature of the diazonium functionality has additionally led to the development of many new reactions including several carbon-carbon bond forming processes. It is therefore highly desirable to determine optimum conditions for the formation of diazonium compounds utilizing the latest processing tools such as flow chemistry to take advantage of the increased safety and continuous manufacturing capabilities. Herein we report a series of flow-based procedures to prepare diazonium salts for subsequent in-situ consumption. Full article

(This article belongs to the Special Issue Recent Synthetic Aspects on the Chemistry of Nitro, Nitroso and Amino Compounds)

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15 pages, 4739 KiB

Open AccessArticle

DNA Cleavage and Condensation Activities of Mono- and Binuclear Hybrid Complexes and Regulation by Graphene Oxide

by Shuo Li^1,2, Mingxing Dai², Chunping Zhang^3,*, Bingying Jiang², Junqiang Xu², Dewen Zhou² and Zhongwei Gu^1,*

¹ National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China

² School of Chemical Engineering, Chongqing University of Technology, Chongqing 400054, China

³ Jiangsu Key Laboratory of Target Drug and Clinical Application, Xuzhou Medical College, Xuzhou 221004, China

Molecules 2016, 21(7), 920; https://doi.org/10.3390/molecules21070920 - 15 Jul 2016

Cited by 11 | Viewed by 6833

Abstract

Hybrid complexes with N,N′-bis(2-benzimidazolylmethyl)amine and cyclen moieties are novel enzyme mimics and controlled DNA release materials, which could interact with DNA through three models under different conditions. In this paper, the interactions between plasmid DNA and seven different complexes were [...] Read more.

Hybrid complexes with N,N′-bis(2-benzimidazolylmethyl)amine and cyclen moieties are novel enzyme mimics and controlled DNA release materials, which could interact with DNA through three models under different conditions. In this paper, the interactions between plasmid DNA and seven different complexes were investigated, and the methods to change the interaction patterns by graphene oxide (GO) or concentrations were also investigated. The cleavage of pUC19 DNA promoted by target complexes were via hydrolytic or oxidative mechanisms at low concentrations ranging from 3.13 × 10⁻⁷ to 6.25 × 10⁻⁵ mol/L. Dinuclear complexes 2a and 2b can promote the cleavage of plasmid pUC19 DNA to a linear form at pH values below 7.0. Furthermore, binuclear hybrid complexes could condense DNA as nanoparticles above 3.13 × 10⁻⁵ mol/L and partly release DNA by graphene oxide with π-π stacking. Meanwhile, the results also reflected that graphene oxide could prevent DNA from breaking down. Cell viability assays showed dinuclear complexes were safe to normal human hepatic cells at relative high concentrations. The present work might help to develop novel strategies for the design and synthesis of DNA controllable releasing agents, which may be applied to gene delivery and also to exploit the new application for GO. Full article

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14 pages, 8885 KiB

Open AccessArticle

Metabolomics Provides Quality Characterization of Commercial Gochujang (Fermented Pepper Paste)

by Gyu Min Lee, Dong Ho Suh, Eun Sung Jung and Choong Hwan Lee^*

Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea

Molecules 2016, 21(7), 921; https://doi.org/10.3390/molecules21070921 - 15 Jul 2016

Cited by 19 | Viewed by 8301

Abstract

To identify the major factors contributing to the quality of commercial gochujang (fermented red pepper paste), metabolites were profiled by mass spectrometry. In principal component analysis, cereal type (wheat, brown rice, and white rice) and species of hot pepper (Capsicum annuum, [...] Read more.

To identify the major factors contributing to the quality of commercial gochujang (fermented red pepper paste), metabolites were profiled by mass spectrometry. In principal component analysis, cereal type (wheat, brown rice, and white rice) and species of hot pepper (Capsicum annuum, C. annuum cv. Chung-yang, and C. frutescens) affected clustering patterns. Relative amino acid and citric acid levels were significantly higher in wheat gochujang than in rice gochujang. Sucrose, linoleic acid, oleic acid, and lysophospholipid levels were high in brown-rice gochujang, whereas glucose, maltose, and γ-aminobutyric acid levels were high in white-rice gochujang. The relative capsaicinoid and luteolin derivative contents in gochujang were affected by the hot pepper species used. Gochujang containing C. annuum cv. Chung-yang and C. frutescens showed high capsaicinoid levels. The luteolin derivative level was high in gochujang containing C. frutescens. These metabolite variations in commercial gochujang may be related to different physicochemical phenotypes and antioxidant activity. Full article

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

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11 pages, 8868 KiB

Open AccessArticle

Evaluation of the Antidepressant Activity, Hepatotoxicity and Blood Brain Barrier Permeability of Methyl Genipin

by Xin Che^1,2,3, Meiyu Wang^1,2,3, Tian Wang^1,2,3,*, Huaying Fan^1,2,3, Mingyan Yang^1,2,3, Wenyan Wang^1,2,3 and Hui Xu^1,2,3

¹ School of Pharmacy, Yantai University, Yantai 264005, China

² Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Yantai 264005, China

³ Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai 264005, China

Molecules 2016, 21(7), 923; https://doi.org/10.3390/molecules21070923 - 16 Jul 2016

Cited by 13 | Viewed by 6026

Abstract

Geniposide (GE) is the main bioactive component of Gardeniae Fructus. The hepatotoxicity of geniposide limited clinical application. In order to get a new geniposide derivative that has less hepatotoxicity and still possesses the antidepressant activity, a new C-1 hydroxyl methylation derivative named methyl [...] Read more.

Geniposide (GE) is the main bioactive component of Gardeniae Fructus. The hepatotoxicity of geniposide limited clinical application. In order to get a new geniposide derivative that has less hepatotoxicity and still possesses the antidepressant activity, a new C-1 hydroxyl methylation derivative named methyl genipin (MG) was synthesized from geniposide. In the present study, we demonstrated that MG did not increase the liver index, alanine aminotransferase (ALT) and aspirate aminotransferase (AST). Histopathological examination suggested that no toxic damages were observed in rats treated orally with MG (0.72 mmol/kg). More importantly, a 7-day treatment with MG at 0.13, 0.26, and 0.52 mmol/kg/day could reduce the duration of immobility. It showed that the antidepressant-like effects of MG were similar to GE in the tail suspension test and the forced swim test. Furthermore, we found MG could be detected in the brain homogenate of mice treated orally with MG 0.52 mmol/kg/day for 1 day by HPLC. The area under the curve (AUC) of MG in the brain homogenate was enhanced to 21.7 times that of GE. The brain amount and distribution speed of MG were improved significantly after oral administration. This study demonstrated that MG possessed the antidepressant effects and could cross the blood–brain barrier, but had less hepatotoxicity. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 836 KiB

Open AccessArticle

An Expeditious and Greener Synthesis of 2-Aminoimidazoles in Deep Eutectic Solvents

by Martina Capua¹, Serena Perrone¹, Filippo Maria Perna²

, Paola Vitale²

, Luigino Troisi¹, Antonio Salomone^1,*

and Vito Capriati^2,*

¹ Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Prov.le Lecce-Monteroni, Lecce I-73100, Italy

² Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari «Aldo Moro», Consorzio C.I.N.M.P.I.S., Via E. Orabona 4, Bari I-70125, Italy

Molecules 2016, 21(7), 924; https://doi.org/10.3390/molecules21070924 - 16 Jul 2016

Cited by 53 | Viewed by 9557

Abstract

A high-yield one-pot two-step synthesis of 2-aminoimidazoles (2-AI), exploiting an under-air heterocyclodehydration process between α-chloroketones and guanidine derivatives, and using deep eutectic solvents (DESs) as nonconventional, “green” and “innocent” reaction media, has been accomplished successfully. The combination of either glycerol or urea with [...] Read more.

A high-yield one-pot two-step synthesis of 2-aminoimidazoles (2-AI), exploiting an under-air heterocyclodehydration process between α-chloroketones and guanidine derivatives, and using deep eutectic solvents (DESs) as nonconventional, “green” and “innocent” reaction media, has been accomplished successfully. The combination of either glycerol or urea with choline chloride (ChCl) proved to be effective for decreasing the reaction time to about 4–6 h in contrast to the 10–12 h usually required for the same reaction run in toxic and volatile organic solvents and under an argon atmosphere. In addition, the use of the ChCl–urea as a DES also enables the direct isolation of triaryl-substituted 2-AI derivatives by means of a simple work-up procedure consisting in filtration and crystallization, and allows the recycle of the DES mixture. A plausible mechanism highlighting the potential role played by hydrogen bonding catalysis has also been illustrated. Full article

(This article belongs to the Special Issue Organic Reaction in Green Solvents)

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11 pages, 931 KiB

Open AccessArticle

A New Class of Glucosyl Thioureas: Synthesis and Larvicidal Activities

by Ping-An Wang^1,*,†, Jun-Tao Feng^2,†, Xing-Zi Wang¹ and Mu-Qiong Li¹

¹ Department of Medicinal Chemistry, School of Pharmacy, The Fourth Military Medical University, Changle West Road 169, Xi’an 710032, China

² Research & Department Center of Biorational Pesticides, Northwest Agriculture & Forestry University, No. 3 Taicheng Road, Yangling 712100, China

^† These authors contributed equally to this work.

Molecules 2016, 21(7), 925; https://doi.org/10.3390/molecules21070925 - 16 Jul 2016

Cited by 5 | Viewed by 5349

Abstract

A novel series of glucosyl thioureas were synthesized in good overall yields (up to 37% over four steps) from d-glucose and primary amines, and their larvicidal activities toward Mythimna separata Walker were also investigated. This new class of glucosyl thioureas demonstrated low [...] Read more.

A novel series of glucosyl thioureas were synthesized in good overall yields (up to 37% over four steps) from d-glucose and primary amines, and their larvicidal activities toward Mythimna separata Walker were also investigated. This new class of glucosyl thioureas demonstrated low to moderate growth inhibition activity of Mythiman separata Walker, with a growth inhibitory rate of up to 47.5% at a concentration of 100.0 mg/L in acetone. Full article

(This article belongs to the Special Issue Synthesis of Bioactive Compounds from the Chiral Pool)

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8 pages, 1709 KiB

Open AccessArticle

Layered Double Hydroxide as a Vehicle to Increase Toxicity of Gallate Ions against Adenocarcinoma Cells

by Jenny Arratia-Quijada¹, Selma Rivas-Fuentes², Karina J. Parra Saavedra³, Adriana M. Macías Lamas⁴ and Gregorio Guadalupe Carbajal Arízaga^3,*

¹ Departamento de Ciencias de la Salud, Centro Universitario de Tonalá, Universidad de Guadalajara, Avenida Nuevo Periférico 555, 48525 Tonalá, Jalisco, Mexico

² Departamento de Bioquímica, Instituto Nacional de Enfermedades Respiratorias, Calzada de Tlalpan 4502, 14080 Mexico City, Mexico

³ Departamento de Química, Universidad de Guadalajara, Marcelino García Barragán 1421, 44430 Guadalajara, Jalisco, Mexico

⁴ Departamento de Farmacobiología, Universidad de Guadalajara, Marcelino García Barragán 1421, 44430 Guadalajara, Jalisco, Mexico

Molecules 2016, 21(7), 928; https://doi.org/10.3390/molecules21070928 - 16 Jul 2016

Cited by 9 | Viewed by 5959

Abstract

The antineoplasic activity of gallic acid has been reported. This compound induces apoptosis and inhibits the growth of several neoplasic cells. However, this molecule is easily oxidized and degraded in the body. The aim of this work was to intercalate gallate ions into [...] Read more.

The antineoplasic activity of gallic acid has been reported. This compound induces apoptosis and inhibits the growth of several neoplasic cells. However, this molecule is easily oxidized and degraded in the body. The aim of this work was to intercalate gallate ions into layered double hydroxide (LDH) nanoparticles under controlled conditions to reduce oxidation of gallate and to evaluate its toxicity against the A549 adenocarcinoma cell line. An isopropanol medium under nitrogen atmosphere was adequate to intercalate gallate ions with a lesser oxidation degree as detected by electron spin resonance spectroscopy. Concentrations of the hybrid LDH-gallate nanoparticles between 0.39 and 25 µg/mL reduced the cell viability to 67%, while the value reached with the pure gallic acid and LDH was 90% and 78%, respectively, thus proving that the combination of gallate ions with the inorganic nanoparticles increases the toxicity potential within this dose range. Full article

(This article belongs to the Collection Nanomedicine)

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15 pages, 1552 KiB

Open AccessArticle

Synthesis of New 3-Heteroarylindoles as Potential Anticancer Agents

by Abdou O. Abdelhamid¹

, Sobhi M. Gomha^1,*

, Nadia A. Abdelriheem¹ and Saher M. Kandeel²

¹ Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt

² Chemistry of Natural Compounds, Department National Research Center, Dokki 12622, Egypt

Molecules 2016, 21(7), 929; https://doi.org/10.3390/molecules21070929 - 16 Jul 2016

Cited by 62 | Viewed by 7279

Abstract

2-(3-(1H-Indol-3-yl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-4-substituted-5-(substituted diazenyl)thiazoles and 2-(1H-indol-3-yl)-9-substituted-4,7-disubstituted pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrimidin-5(7H)-ones were synthesized via reaction of hydrazonoyl halides with each of 3-(1H-indol-2-yl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide and 7-(1H-indol-3-yl)-2- thioxo-5-substituted-2,3-dihydropyrido[2,3-d]pyrimidin-4(1 [...] Read more.

2-(3-(1H-Indol-3-yl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-4-substituted-5-(substituted diazenyl)thiazoles and 2-(1H-indol-3-yl)-9-substituted-4,7-disubstituted pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrimidin-5(7H)-ones were synthesized via reaction of hydrazonoyl halides with each of 3-(1H-indol-2-yl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide and 7-(1H-indol-3-yl)-2- thioxo-5-substituted-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones, respectively. Also, hydrazonoyl halides were reacted with N’-(1-(1H-indol-3-yl)ethylidene)-2-cyanoacetohydrazide to afford 1,3,4-thiadiazole derivatives. Structures of the new synthesis were elucidated on the basis of elemental analysis, spectral data, and alternative synthetic routes whenever possible. Fifteen of the new compounds have been evaluated for their antitumor activity against the MCF-7 human breast carcinoma cell line. The results indicated that many of the tested compounds showed moderate to high anticancer activity when compared with doxorubicin as a reference drug. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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17 pages, 1690 KiB

Open AccessArticle

Quantitative Determination of Alkaloids in Lotus Flower (Flower Buds of Nelumbo nucifera) and Their Melanogenesis Inhibitory Activity

by Toshio Morikawa^1,2,†

, Niichiro Kitagawa^1,3,†, Genzoh Tanabe⁴

, Kiyofumi Ninomiya^1,2, Shuhei Okugawa^1,3, Chiaki Motai^1,3, Iyori Kamei¹, Masayuki Yoshikawa¹, I-Jung Lee⁵ and Osamu Muraoka^1,2,4,*

¹ Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan

² Antiaging Center, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan

³ Koshiro Company Ltd., 2-5-8 Doshomachi, Chuo-ku, Osaka 541-0045, Japan

⁴ Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan

⁵ National Research Institute of Chinese Medicine, 155-1, Sec. 2, Linong St., Beitou District, Taipei 11221, Taiwan

^† These authors contributed equally to this work.

Molecules 2016, 21(7), 930; https://doi.org/10.3390/molecules21070930 - 19 Jul 2016

Cited by 43 | Viewed by 10412

Abstract

A quantitative analytical method for five aporphine alkaloids, nuciferine (1), nornuciferine (2), N-methylasimilobine (3), asimilobine (4), and pronuciferine (5), and five benzylisoquinoline alkaloids, armepavine (6), norarmepavine (7), N [...] Read more.

A quantitative analytical method for five aporphine alkaloids, nuciferine (1), nornuciferine (2), N-methylasimilobine (3), asimilobine (4), and pronuciferine (5), and five benzylisoquinoline alkaloids, armepavine (6), norarmepavine (7), N-methylcoclaurine (8), coclaurine (9), and norjuziphine (10), identified as the constituents responsible for the melanogenesis inhibitory activity of the extracts of lotus flowers (the flower buds of Nelumbo nucifera), has been developed using liquid chromatography-mass spectrometry. The optimum conditions for separation and detection of these 10 alkaloids were achieved on a πNAP column, a reversed-phase column with naphthylethyl group-bonded silica packing material, with CH₃CN–0.2% aqueous acetic acid as the mobile phase and using mass spectrometry equipped with a positive-mode electrospray ionization source. According to the protocol established, distributions of these 10 alkaloids in the petal, receptacle, and stamen parts, which were separated from the whole flower, were examined. As expected, excellent correlations were observed between the total alkaloid content and melanogenesis inhibitory activity. Among the active alkaloids, nornuciferine (2) was found to give a carbamate salt (2′′) via formation of an unstable carbamic acid (2′) by absorption of carbon dioxide from the air. Full article

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

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11 pages, 1377 KiB

Open AccessArticle

Characterization and Prebiotic Effect of the Resistant Starch from Purple Sweet Potato

by Yafeng Zheng^1,2, Qi Wang^1,3, Baoyu Li^1,2, Liangmei Lin^1,2, Rosa Tundis⁴, Monica R. Loizzo⁴, Baodong Zheng^1,2

and Jianbo Xiao^1,*

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

² Fujian Provincial Key Laboratory of Quality Science and Processing Technology in Special Starch, Fuzhou 350002, China

³ Institute of Agricultural Engineering, Fujian Academy of Agriculture Sciences, Fuzhou 350003, China

⁴ Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via P. Bucci, 87036 Rende (CS), Italy

Molecules 2016, 21(7), 932; https://doi.org/10.3390/molecules21070932 - 19 Jul 2016

Cited by 60 | Viewed by 10501

Abstract

Purple sweet potato starch is a potential resource for resistant starch production. The effects of heat-moisture treatment (HMT) and enzyme debranching combined heat-moisture treatment (EHMT) on the morphological, crystallinity and thermal properties of PSP starches were investigated. The results indicated that, after HMT [...] Read more.

Purple sweet potato starch is a potential resource for resistant starch production. The effects of heat-moisture treatment (HMT) and enzyme debranching combined heat-moisture treatment (EHMT) on the morphological, crystallinity and thermal properties of PSP starches were investigated. The results indicated that, after HMT or EHMT treatments, native starch granules with smooth surface was destroyed to form a more compact, irregular and sheet-like structure. The crystalline pattern was transformed from C-type to B-type with decreasing relative crystallinity. Due to stronger crystallites formed in modified starches, the swelling power and solubility of HMT and EHMT starch were decreased, while the transition temperatures and gelatinization enthalpy were significantly increased. In addition, HMT and EHMT exhibited greater effects on the proliferation of bifidobacteria compared with either glucose or high amylose maize starch. Full article

(This article belongs to the Special Issue Selected papers from 2nd International Symposium on Phytochemicals in Medicine and Food (2-ISPMF, Fuzhou, 2017))

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15 pages, 4852 KiB

Open AccessArticle

Aberrant Expression of Novel Cytokine IL-38 and Regulatory T Lymphocytes in Childhood Asthma

by Man Chu^1,2, Ida M.T. Chu^1,2, Edmund C.M. Yung³, Christopher W.K. Lam⁴, Ting F. Leung³, Gary W.K. Wong^3,* and Chun K. Wong^1,2,5,*

¹ Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China

² Shenzhen Research Institute, The Chinese University of Hong Kong, 518057 Shenzhen, China

³ Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China

⁴ State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau, China

⁵ Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, China

Molecules 2016, 21(7), 933; https://doi.org/10.3390/molecules21070933 - 18 Jul 2016

Cited by 52 | Viewed by 6959

Abstract

We investigated the expression of novel anti-inflammatory interleukin (IL)-38 and regulatory T (Treg) lymphocytes in childhood asthma patients. The protein and mRNA expression level of IL-38, periostin, peripheral CD4⁺CD25⁺CD134⁺ T lymphocytes as well as CD4⁺CD25^high [...] Read more.

We investigated the expression of novel anti-inflammatory interleukin (IL)-38 and regulatory T (Treg) lymphocytes in childhood asthma patients. The protein and mRNA expression level of IL-38, periostin, peripheral CD4⁺CD25⁺CD134⁺ T lymphocytes as well as CD4⁺CD25^highFoxP3⁺ and CD4⁺CD25^highCD127⁻ Treg lymphocytes from 40 asthmatic patients and 20 normal control (NC) subjects were studied using ELISA, qPCR and flow cytometry. Serum and supernatant cytokines/chemokines were determined by multiplex assay. Serum IL-38, IL-5, IL-17, IL-6, interferon-γ, periostin, IL-1β and IL-13 concentrations were significantly higher in asthmatic patients with or without steroid treatment than those in controls (all p < 0.05). The percentages of both CD4⁺CD25^highFoxP3⁺ and CD4⁺CD25^highCD127⁻ Treg lymphocytes were markedly decreased in asthmatic patients with and without steroid treatment than those in controls (all p < 0.05). The elevated IL-38 concentration negatively correlated with the percentage of Treg lymphocytes in asthmatic patients with high level (>40 ng/mL) of periostin (p < 0.05). Although the comparable mRNA levels of IL-38 and its receptor IL-36R were found between patients and controls, the mRNA level of IL-38 positively correlated with IL-36R and negatively correlated with IL-10 in all asthmatic patients (both p < 0.05). The percentage of CD4⁺CD25⁺CD134⁺ activated T lymphocytes was also significantly higher in asthmatic patients with steroid treatment than those in controls (p < 0.05). This cross-sectional study demonstrated that the overexpression of circulating IL-38 may play a role in the immunopathogenesis in asthma. Full article

(This article belongs to the Special Issue Molecules Mediating Allergic and Autoimmune Inflammation: Commemorative Issue in Honor of Professor Christopher W. K. Lam’s Research Achievements on the Occasion of His 70th Birthday)

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12 pages, 2934 KiB

Open AccessArticle

Protocatechualdehyde Induces S-Phase Arrest and Apoptosis by Stimulating the p27^KIP1-Cyclin A/D1-CDK2 and Mitochondrial Apoptotic Pathways in HT-29 Cells

by Shi Zhong, You-Gui Li, Dong-Feng Ji^*, Tian-Bao Lin and Zhi-Qiang Lv

Sericultural Research Institute, Zhejiang Academy of Agricultural Science, Hangzhou 310021, China

Molecules 2016, 21(7), 934; https://doi.org/10.3390/molecules21070934 - 19 Jul 2016

Cited by 30 | Viewed by 7534

Abstract

Protocatechualdehyde (PCA) extracted from Phellinus gilvus exhibits anti-cancer activity in human colorectal carcinoma cells (HT-29). However, the underlying mechanisms remain poorly understood. We performed an in vitro study involving MTT, flow cytometry, RT-PCR, and western blot analyses to investigate the effects of PCA [...] Read more.

Protocatechualdehyde (PCA) extracted from Phellinus gilvus exhibits anti-cancer activity in human colorectal carcinoma cells (HT-29). However, the underlying mechanisms remain poorly understood. We performed an in vitro study involving MTT, flow cytometry, RT-PCR, and western blot analyses to investigate the effects of PCA treatment on cell proliferation, cell cycle distribution, apoptosis, and expression of several cell cycle-related genes in HT-29 cells. The treatment enhanced S-phase cell cycle and apoptosis in HT-29 cells in a dose-dependent manner. Western blot results showed that PCA treatment decreased the expression levels of cyclin A, cyclin D1, and p27^KIP1 but increased those of cyclin-dependent kinase 2 (CDK2) in HT-29 cells. Furthermore, the expression levels of B-cell lymphoma/leukemia-2 (Bcl-2) and B-cell lymphoma/leukemia-xL (Bcl-xL) were down-regulated, whereas the levels of BH3-interacting domain death agonist (Bid), Bcl-2 homologous antagonist/killer (Bak), and cytosolic cytochrome c were significantly upregulated. Thus, the enzymes caspases-9, -3, -8, and -6 were found to be activated in HT-29 cells with PCA treatment. These results indicate that PCA-induced S-phase cell cycle arrest and apoptosis involve p27^KIP1-mediated activation of the cyclin-A/D1-Cdk2 signaling pathway and the mitochondrial apoptotic pathway. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 863 KiB

Open AccessArticle

Synthesis, Spectral Characterization of Several Novel Pyrene-Derived Aminophosphonates and Their Ecotoxicological Evaluation Using Heterocypris incongruens and Vibrio fisheri Tests

by Jarosław Lewkowski^1,*

, Maria Rodriguez Moya¹, Marta Chmielak^1,†, Diana Rogacz², Kamila Lewicka² and Piotr Rychter^2,*

¹ Department of Organic Chemistry, Faculty of Chemistry, University of Łódź, Tamka 12, 91-403 Łódź, Poland

² Institute of Chemistry, Environmental Protection and Biotechnology, Jan Długosz University in Częstochowa, 13/15 Armii Krajowej Av., 42-200 Częstochowa, Poland

^† M.Sc. student at the Faculty of Chemistry, University of Łódź (Academic Year 2015–2016).

Molecules 2016, 21(7), 936; https://doi.org/10.3390/molecules21070936 - 19 Jul 2016

Cited by 12 | Viewed by 6201

Abstract

Four diphenyl pyrene-derived aminophosphonates were synthesized. Attempts were made to synthesize diphenyl N-(R)-α-methylbenzylamino(pyren-1-yl)methylphosphonate (3e) in order to obtain the chiral aminophosphonate bearing a pyrene moiety. Because these attempts failed, dimethyl and dibenzyl N-(R)-α-methylbenzyl substituted aminophosphonates [...] Read more.

Four diphenyl pyrene-derived aminophosphonates were synthesized. Attempts were made to synthesize diphenyl N-(R)-α-methylbenzylamino(pyren-1-yl)methylphosphonate (3e) in order to obtain the chiral aminophosphonate bearing a pyrene moiety. Because these attempts failed, dimethyl and dibenzyl N-(R)-α-methylbenzyl substituted aminophosphonates 4 and 5 were synthesized and the predominant diastereoisomer of dimethyl aminophosphonate 4 was isolated. The resolution of the diastereomeric mixture of 5 failed. Aminophosphonates 3a–d and the predominant diastereoisomer of 4 were investigated in terms of their ecotoxicity using tests performed on the ostracode Heterocypris incongruens and the fluorescent bacterium Vibrio fisheri. The tests confirmed the moderate-to-high ecotoxicity of aminophosphonates 3a–d and 4, but no evident correlation between the structure and toxicity has been found. Full article

(This article belongs to the Special Issue Recent Advances in Organophosphorus Chemistry)

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12 pages, 388 KiB

Open AccessArticle

Structures and Biogenesis of Fallaxosides D₄, D₅, D₆ and D₇, Trisulfated Non-Holostane Triterpene Glycosides from the Sea Cucumber Cucumaria fallax

by Alexandra S. Silchenko¹, Anatoly I. Kalinovsky¹, Sergey A. Avilov¹, Pelageya V. Andryjaschenko¹, Pavel S. Dmitrenok¹, Vladimir I. Kalinin¹, Ekaterina A. Chingizova¹, Kirill V. Minin² and Valentin A. Stonik^1,*

¹ G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Pr. 100-letya Vladivostoka 159, 690022 Vladivostok, Russia

² P.P. Shirshov Institute of Oceanology of the Russian Academy of Sciences, Nakhimovsky Pr., 36, 117997 Moscow, Russia

Molecules 2016, 21(7), 939; https://doi.org/10.3390/molecules21070939 - 20 Jul 2016

Cited by 14 | Viewed by 5438

Abstract

Four new trisulfated triterpene glycosides, fallaxosides D₄ (1), D₅ (2), D₆ (3) and D₇ (4) have been isolated from the sea cucumber Cucumaria fallax (Cucumariidae, Dendrochirotida). The structures of the glycosides [...] Read more.

Four new trisulfated triterpene glycosides, fallaxosides D₄ (1), D₅ (2), D₆ (3) and D₇ (4) have been isolated from the sea cucumber Cucumaria fallax (Cucumariidae, Dendrochirotida). The structures of the glycosides have been elucidated by 2D NMR spectroscopy and HRESIMS. All the glycosides have the lanostane aglycones of a rare non-holostane type with 7(8)-, 8(9)- or 9(11)-double bonds, one or two hydroxyl groups occupying unusual positions in the polycyclic nucleus and shortened or normal side chains. The pentasaccharide carbohydrate moieties of 1–4 have three sulfate groups. The cytotoxic activity of glycosides 1–4 against the ascite form of mouse Ehrlich carcinoma cells and mouse spleen lymphocytes and hemolytic activity against mouse erythrocytes have been studied. Full article

(This article belongs to the Collection Triterpenes and Triterpenoids)

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8 pages, 3331 KiB

Open AccessArticle

Asperpyrone-Type Bis-Naphtho-γ-Pyrones with COX-2–Inhibitory Activities from Marine-Derived Fungus Aspergillus niger

by Wei Fang^1,†, Xiuping Lin^2,†, Jianjiao Wang³, Yonghong Liu², Huaming Tao^4,*

and Xuefeng Zhou^2,*

¹ Hubei Biopesticide Engineering Research Center, Hubei Academy of Agricultural Science, Wuhan 430064, China

² Key Laboratory of Tropical Marine Bio-Resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China

³ Department of Pharmacy, Medical College, Wuhan University of Science and Technology, Wuhan 430065, China

⁴ School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China

^† These authors contributed equally to this paper.

Molecules 2016, 21(7), 941; https://doi.org/10.3390/molecules21070941 - 20 Jul 2016

Cited by 24 | Viewed by 7577

Abstract

Bis-naphtho-γ-pyrones (BNPs) are an important group of aromatic polyketides derived from fungi, and asperpyrone-type BNPs are produced primarily by Aspergillus species. The fungal strain Aspergillus niger SCSIO Jcsw6F30, isolated from a marine alga, Sargassum sp., and identified according to its morphological traits and [...] Read more.

Bis-naphtho-γ-pyrones (BNPs) are an important group of aromatic polyketides derived from fungi, and asperpyrone-type BNPs are produced primarily by Aspergillus species. The fungal strain Aspergillus niger SCSIO Jcsw6F30, isolated from a marine alga, Sargassum sp., and identified according to its morphological traits and the internal transcribed spacer (ITS) region sequence, was studied for BNPs secondary metabolisms. After HPLC/MS analysis of crude extract of the fermentation broth, 11 asperpyrone-type BNPs were obtained directly and quickly by chromatographic separation in the extract, and those isolated asperpyrone-type BNPs were structurally identified by NMR and MS analyses. All of the BNPs showed weak cytotoxicities against 10 human tumor cells (IC₅₀ > 30 μM). However, three of them, aurasperone F (3), aurasperone C (6) and asperpyrone A (8), exhibited obvious COX-2–inhibitory activities, with the IC₅₀ values being 11.1, 4.2, and 6.4 μM, respectively. This is the first time the COX-2–inhibitory activities of BNPs have been reported. Full article

(This article belongs to the Special Issue Natural Products and Inflammation)

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14 pages, 4529 KiB

Open AccessArticle

Photoelectrochemical Behavior of Electrophoretically Deposited Hematite Thin Films Modified with Ti(IV)

by Nicola Dalle Carbonare^1,*, Rita Boaretto¹, Stefano Caramori^1,*, Roberto Argazzi², Maurizio Dal Colle¹

, Luca Pasquini³

, Renzo Bertoncello⁴, Marcello Marelli⁵

, Claudio Evangelisti⁵ and Carlo Alberto Bignozzi¹

¹ Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Via Fossato di Mortara 11–17, 44121 Ferrara, Italy

² CNR/ISOF c/o Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Via Fossato di Mortara 11–17, 44121 Ferrara, Italy

³ Department of Physics and Astronomy, University of Bologna, Viale Berti Pichat 6/2, 40127 Bologna, Italy

⁴ Department of Chemical Sciences, University of Padua, Via F. Marzolo 1, 35131 Padua, Italy

⁵ CNR ISTM, Via Fantoli 16/15, 20138 Milan, Italy

Molecules 2016, 21(7), 942; https://doi.org/10.3390/molecules21070942 - 20 Jul 2016

Cited by 6 | Viewed by 6257

Abstract

Doping hematite with different elements is a common strategy to improve the electrocatalytic activity towards the water oxidation reaction, although the exact effect of these external agents is not yet clearly understood. Using a feasible electrophoretic procedure, we prepared modified hematite films by [...] Read more.

Doping hematite with different elements is a common strategy to improve the electrocatalytic activity towards the water oxidation reaction, although the exact effect of these external agents is not yet clearly understood. Using a feasible electrophoretic procedure, we prepared modified hematite films by introducing in the deposition solution Ti(IV) butoxide. Photoelectrochemical performances of all the modified electrodes were superior to the unmodified one, with a 4-fold increase in the photocurrent at 0.65 V vs. SCE in 0.1 M NaOH (pH 13.3) for the 5% Ti-modified electrode, which was the best performing electrode. Subsequent functionalization with an iron-based catalyst led, at the same potential, to a photocurrent of ca. 1.5 mA·cm⁻², one of the highest achieved with materials based on solution processing in the absence of precious elements. AFM, XPS, TEM and XANES analyses revealed the formation of different Ti(IV) oxide phases on the hematite surface, that can reduce surface state recombination and enhance hole injection through local surface field effects, as confirmed by electrochemical impedance analysis. Full article

(This article belongs to the Special Issue Photocatalytic Water Splitting—the Untamed Dream)

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6 pages, 2046 KiB

Open AccessCommunication

Two New Secondary Metabolites from the Endophytic Fungus Endomelanconiopsis endophytica

by Zhang-Hua Sun^†, Hao-Hua Li^†, Fa-Liang Liang^†, Yu-Chan Chen, Hong-Xin Liu, Sai-Ni Li, Guo-Hui Tan and Wei-Min Zhang^*

¹ State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangzhou 510070, China

^† These authors contributed equally to this work.

Molecules 2016, 21(7), 943; https://doi.org/10.3390/molecules21070943 - 20 Jul 2016

Cited by 10 | Viewed by 5595

Abstract

Two new secondary metabolites, endomeketals A–B (1–2), a new natural product (3), and a known compound (4) were isolated from the ethyl acetate extract of the endophytic fungus Endomelanconiopsis endophytica A326 derived from Ficus hirta [...] Read more.

Two new secondary metabolites, endomeketals A–B (1–2), a new natural product (3), and a known compound (4) were isolated from the ethyl acetate extract of the endophytic fungus Endomelanconiopsis endophytica A326 derived from Ficus hirta. Their structures were determined on the basis of extensive spectroscopic analysis. All compounds were evaluated for their cytotoxic activities against SF-268, MCF-7, NCI-H460, and HepG-2 tumor cell lines. However, no compound showed cytotoxic activity against these human tumor cell lines. Full article

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7 pages, 356 KiB

Open AccessCommunication

Secondary Metabolites Produced by an Endophytic Fungus Pestalotiopsis sydowiana and Their 20S Proteasome Inhibitory Activities

by Xuekui Xia¹, Soonok Kim², Changheng Liu¹ and Sang Hee Shim^3,*

¹ Key Biosensor Laboratory of Shandong Province, Biology Institute, Shandong Academy of Sciences, Jinan 250014, China

² National Institute of Biological Resources, Incheon 22689, Korea

³ Duksung IDC, College of Pharmacy, Duksung Women’s University, Seoul 01369, Korea

Molecules 2016, 21(7), 944; https://doi.org/10.3390/molecules21070944 - 20 Jul 2016

Cited by 17 | Viewed by 5802

Abstract

Fungal endophytes have attracted attention due to their functional diversity. Secondary metabolites produced by Pestalotiopsis sydowiana from a halophyte, Phragmites communis Trinus, were investigated. Eleven compounds, including four penicillide derivatives (1–4) and seven α-pyrone analogues (5–10 [...] Read more.

Fungal endophytes have attracted attention due to their functional diversity. Secondary metabolites produced by Pestalotiopsis sydowiana from a halophyte, Phragmites communis Trinus, were investigated. Eleven compounds, including four penicillide derivatives (1–4) and seven α-pyrone analogues (5–10) were isolated from cultures of P. sydowiana. The compounds were identified based on spectroscopic data. The inhibitory activities against the 20S proteasome were evaluated. Compounds 1–3, 5, and 9–10 showed modest proteasome inhibition activities, while compound 8 showed strong activity with an IC₅₀ of 1.2 ± 0.3 μM. This is the first study on the secondary metabolites produced by P. sydowiana and their proteasome inhibitory activities. The endophytic fungus P. sydowiana might be a good resource for proteasome inhibitors. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 7321 KiB

Open AccessArticle

Intra-Population Variation of Secondary Metabolites in Cistus ladanifer L.

by Cristina Valares Masa, Juan Carlos Alías Gallego

, Natividad Chaves Lobón and Teresa Sosa Díaz^*

Department of Plant Biology, Ecology and Earth Sciences, Faculty of Science, University of Extremadura, 06006 Badajoz, Spain

Molecules 2016, 21(7), 945; https://doi.org/10.3390/molecules21070945 - 21 Jul 2016

Cited by 13 | Viewed by 6659

Abstract

In previous studies, secondary metabolites in the leaf exudate of Cistus ladanifer, specifically aglycone flavonoids and diterpenes, were demonstrated to play an ecophysiological role. They protect against ultraviolet radiation, have antiherbivore activity, and are allelopathic agents. Their synthesis in the plant was [...] Read more.

In previous studies, secondary metabolites in the leaf exudate of Cistus ladanifer, specifically aglycone flavonoids and diterpenes, were demonstrated to play an ecophysiological role. They protect against ultraviolet radiation, have antiherbivore activity, and are allelopathic agents. Their synthesis in the plant was also found to vary quantitatively and qualitatively in response to various environmental factors. In view of these findings, the present work was designed to clarify whether within a single population there are differences among individuals subject to the same environmental conditions. To this end, we analyzed the leaves of 100 individuals of C. ladanifer. The results showed the existence of intrapopulational variation, since, although all the individuals had the same composition of secondary chemistry, the amounts were different. The individuals of a given population of C. ladanifer differ from each other even when growing under similar conditions. According to the ammount of flavonoids and diterpenes observed in each individual, it was possible to distinguish four different groups of individuals. Most individuals, evenly distributed within the population, had low concentrations of the studied compounds, whilst other individuals synthesized greater amounts and were randomly distributed among the former. Given the functions of flavonoids and diterpenes in this species, the quantified intra-population variation may involve greater plasticity for the species in the face of environmental changes. Full article

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

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10 pages, 1357 KiB

Open AccessArticle

A New Method for the Isolation of Ergosterol and Peroxyergosterol as Active Compounds of Hygrophoropsis aurantiaca and in Vitro Antiproliferative Activity of Isolated Ergosterol Peroxide

by Renata Nowak^1,*, Marta Drozd¹, Ewaryst Mendyk², Marta Lemieszek³, Olga Krakowiak¹, Wanda Kisiel⁴, Wojciech Rzeski^3,5 and Katarzyna Szewczyk¹

¹ Department of Pharmaceutical Botany, Medical University of Lublin, 1 Chodźki Str., 20-093 Lublin, Poland

² Analytical Laboratory, Faculty of Chemistry, University of Maria Curie-Sklodowska, 3/27 M.C. Skłodowska Sq., 20-031 Lublin, Poland

³ Department of Medical Biology, Institute of Rural Health, 2 Jaczewskiego Str., 20-090 Lublin, Poland

⁴ Department of Phytochemistry, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Str., 31-343 Kraków, Poland

⁵ Department of Virology and Immunology, Institute of Microbiology and Biotechnology, University of Maria Curie-Sklodowska, 19 Akademicka Str., 20-033 Lublin, Poland

Molecules 2016, 21(7), 946; https://doi.org/10.3390/molecules21070946 - 21 Jul 2016

Cited by 63 | Viewed by 9605

Abstract

In the present study, ergosterol peroxide and ergosterol were isolated for the first time from fresh fruit bodies of Hygrophoropsis aurantiaca (False Chanterelle). The substances were characterized mainly by spectroscopic methods (¹H-NMR, ¹³C-NMR, DEPT-45, DEPT-90, DEPT-135, 2D-NMR). In our study, [...] Read more.

In the present study, ergosterol peroxide and ergosterol were isolated for the first time from fresh fruit bodies of Hygrophoropsis aurantiaca (False Chanterelle). The substances were characterized mainly by spectroscopic methods (¹H-NMR, ¹³C-NMR, DEPT-45, DEPT-90, DEPT-135, 2D-NMR). In our study, a new specific thin layer chromatographic method was developed for determination of ergosterol and ergosterol peroxide in H. aurantiaca extract. The method is based on the separation of n-hexane extract on silica gel (Silica Gel G) TLC plates using the optimized solvent system toluene/ethyl acetate (3:1; v/v). The main advantages of the developed method are the simplicity of operation and the low cost. The in vitro study results revealed the antiproliferative properties of ergosterol peroxide against LS180 human colon cancer cells. The described effect was attributed both to altered mitochondrial activity and decreased DNA synthesis. Additionally, in the same concentration range the investigated compound was not toxic to CCD 841 CoTr human colon epithelial cells. The present study suggests that fruit bodies of H. aurantiaca have great potential for producing substances and extracts with potential applications in medicine. Full article

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8 pages, 1278 KiB

Open AccessCommunication

Identification of Chemical Composition of Leaves and Flowers from Paeonia rockii by UHPLC-Q-Exactive Orbitrap HRMS

by Jinhua Li¹, Gang Kuang², Xiaohu Chen³ and Rui Zeng^1,*

¹ College of Pharmacy, Southwest University for Nationalities, Chengdu 610041, China

² Department of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, China

³ Chongqing Institute for Food and Drug Control, Chongqing 401120, China

Molecules 2016, 21(7), 947; https://doi.org/10.3390/molecules21070947 - 21 Jul 2016

Cited by 44 | Viewed by 9348

Abstract

The Paeonia genus, an important source of crude drugs, has been extensively used in traditional Chinese medicine (TCM) to treat cardiovascular and female-related diseases. Although many peony species have been investigated, the study of Paeonia rockii is still quite limited, especially its chemical [...] Read more.

The Paeonia genus, an important source of crude drugs, has been extensively used in traditional Chinese medicine (TCM) to treat cardiovascular and female-related diseases. Although many peony species have been investigated, the study of Paeonia rockii is still quite limited, especially its chemical composition. Here, an advanced ultra-high-performance liquid chromatography (UHPLC) analytical technique combined with Q-Exactive Orbitrap hybrid quadrupole-Orbitrap mass spectrometry utilizing high-resolution full MS and MS/MS scan modes was applied to screen and identify the chemical constituents of this species. As a result, a total of 46 compounds were characterized, including 11 monoterpene glycosides, five phenolic acids, six tannins and 24 flavonoids. Among them, 16 compounds were reported for the first time in Paeonia rockii. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 4868 KiB

Open AccessArticle

Stability and Degradation of Caffeoylquinic Acids under Different Storage Conditions Studied by High-Performance Liquid Chromatography with Photo Diode Array Detection and High-Performance Liquid Chromatography with Electrospray Ionization Collision-Induced Dissociation Tandem Mass Spectrometry

by Meng Xue^1,†, Hang Shi^1,†, Jiao Zhang¹, Qing-Quan Liu², Jun Guan¹, Jia-Yu Zhang^3,* and Qun Ma^1,*

¹ School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China

² Beijing Hospital of Traditional Chinese Medicine, Beijing 100010, China

³ Beijing Institution of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China

^† These authors contributed equally to this work.

Molecules 2016, 21(7), 948; https://doi.org/10.3390/molecules21070948 - 21 Jul 2016

Cited by 73 | Viewed by 9265

Abstract

Caffeoylquinic acids (CQAs) are main constituents in many herbal medicines with various biological and pharmacological effects. However, CQAs will degrade or isomerize when affected by temperature, pH, light, etc. In this study, high-performance liquid chromatography with photodiode array detection (HPLC-PDA) and high-performance liquid [...] Read more.

Caffeoylquinic acids (CQAs) are main constituents in many herbal medicines with various biological and pharmacological effects. However, CQAs will degrade or isomerize when affected by temperature, pH, light, etc. In this study, high-performance liquid chromatography with photodiode array detection (HPLC-PDA) and high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was utilized to study the stability and degradation of CQAs (three mono-acyl CQAs and four di-acyl CQAs) under various ordinary storage conditions (involving different temperatures, solvents, and light irradiation). The results indicated that the stability of CQAs was mainly affected by temperature and light irradiation, while solvents did not affect it in any obvious way under the conditions studied. Mono-acyl CQAs were generally much more stable than di-acyl CQAs under the same conditions. Meanwhile, the chemical structures of 30 degradation products were also characterized by HPLC-MSⁿ, inferring that isomerization, methylation, and hydrolysis were three major degradation pathways. The result provides a meaningful clue for the storage conditions of CQAs standard substances and samples. Full article

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10 pages, 1418 KiB

Open AccessArticle

Novel Improved Synthesis of HSP70 Inhibitor, Pifithrin-μ. In Vitro Synergy Quantification of Pifithrin-μ Combined with Pt Drugs in Prostate and Colorectal Cancer Cells

by Aoife M. McKeon¹, Alan Egan²

, Jay Chandanshive¹, Helena McMahon² and Darren M. Griffith^1,*

¹ Centre for Synthesis and Chemical Biology, Department of Pharmaceutical and Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St. Stephens Green, Dublin 2 D02 YN77, Ireland

² Shannon ABC, South Campus, IT Tralee, Clash, Tralee, Co., Kerry V92 CX88, Ireland

Molecules 2016, 21(7), 949; https://doi.org/10.3390/molecules21070949 - 21 Jul 2016

Cited by 35 | Viewed by 7780 | Correction

Abstract

We describe a novel improved approach to the synthesis of the important and well-known heat shock protein 70 inhibitor (HSP70), pifithrin-μ, with corresponding and previously unreported characterisation. The first example of a combination study comprising HSP70 inhibitor pifithrin-μ and cisplatin or oxaliplatin is [...] Read more.

We describe a novel improved approach to the synthesis of the important and well-known heat shock protein 70 inhibitor (HSP70), pifithrin-μ, with corresponding and previously unreported characterisation. The first example of a combination study comprising HSP70 inhibitor pifithrin-μ and cisplatin or oxaliplatin is reported. We have determined, using the Chou-Talalay method, (i) moderate synergistic and synergistic effects in co-treating PC-3 prostate cancer cells with pifithrin-μ and cisplatin and (ii) significant synergistic effects including strong synergism in cotreating HT29 colorectal cancer cells with oxaliplatin and pifithrin-μ. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 2091 KiB

Open AccessArticle

Application of Ultrasound in a Closed System: Optimum Condition for Antioxidants Extraction of Blackberry (Rubus fructicosus) Residues

by Quinatzin Y. Zafra-Rojas¹, Nelly S. Cruz-Cansino², Aurora Quintero-Lira¹, Carlos A. Gómez-Aldapa³

, Ernesto Alanís-García², Alicia Cervantes-Elizarrarás¹, Norma Güemes-Vera¹ and Esther Ramírez-Moreno^2,*

¹ Instituto de Ciencias Agropecuarias, Universidad Autónoma del Estado de Hidalgo, Av. Universidad Km 1, Rancho Universitario, Tulancingo de Bravo, Hidalgo 43600, Mexico

² Centro de Investigación Interdisciplinario, Área Académica de Nutrición, Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Circuito Actopan-Tilcuautla s/n. Ex hacienda La Concepción, San Agustín Tlaxiaca, Hidalgo 42160, Mexico

³ Centro de Investigaciones Químicas, Instituto de Ciencias Básicas e Ingeniería, Universidad Autónoma del Estado de Hidalgo, Centro Universitario, Carretera Pachuca-Tulancingo Km 4.5, Mineral de la Reforma, Hidalgo 42183, Mexico

Molecules 2016, 21(7), 950; https://doi.org/10.3390/molecules21070950 - 21 Jul 2016

Cited by 20 | Viewed by 6486

Abstract

Blackberry processing generates up to 20% of residues composed mainly of peel, seeds and pulp that are abundant in flavonoids. The objective of this study was to optimize the ultrasound conditions, in a closed system, for antioxidants extraction, using the response surface methodology. [...] Read more.

Blackberry processing generates up to 20% of residues composed mainly of peel, seeds and pulp that are abundant in flavonoids. The objective of this study was to optimize the ultrasound conditions, in a closed system, for antioxidants extraction, using the response surface methodology. Blackberry (Rubus fructicosus) residues were analyzed for total phenolics, total anthocyanins, and antioxidant activity by ABTS and DPPH. The selected independent variables were ultrasound amplitude (X₁: 80%–90%) and extraction time (X₂: 10–15 min), and results were compared with conventional extraction methods. The optimal conditions for antioxidants extraction were 91% amplitude for 15 min. The results for total phenolic content and anthocyanins and antioxidant activity by ABTS and DPPH were of 1201.23 mg gallic acid equivalent (GAE)/100 g dry weight basis (dw); 379.12 mg/100 g·dw; 6318.98 µmol Trolox equivalent (TE)/100 g·dw and 9617.22 µmol TE/100 g·dw, respectively. Compared to solvent extraction methods (water and ethanol), ultrasound achieved higher extraction of all compounds except for anthocyanins. The results obtained demonstrated that ultrasound is an alternative to improve extraction yield of antioxidants from fruit residues such as blackberry. Full article

(This article belongs to the Special Issue Sonochemistry and Green Chemistry Applications)

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13 pages, 8646 KiB

Open AccessArticle

Protective Effect of the Total Flavonoids from Rosa laevigata Michx Fruit on Renal Ischemia-Reperfusion Injury through Suppression of Oxidative Stress and Inflammation

by Lisha Zhao, Lina Xu, Xufeng Tao, Xu Han, Lianhong Yin, Yan Qi^* and Jinyong Peng^*

College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China

Molecules 2016, 21(7), 952; https://doi.org/10.3390/molecules21070952 - 21 Jul 2016

Cited by 64 | Viewed by 9660 | Correction

Abstract

Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Our previous studies have shown that the total flavonoids (TFs) from Rosa laevigata Michx fruit has various activities, however, there were no papers reporting the role of the TFs against [...] Read more.

Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Our previous studies have shown that the total flavonoids (TFs) from Rosa laevigata Michx fruit has various activities, however, there were no papers reporting the role of the TFs against renal IRI. In the present work, a hypoxia/reoxygenation (H/R) model in NRK-52E cells and ischemia-reperfusion model in rats were used. The results showed that the TFs significantly attenuated cell injury and markedly decreased serum creatinine (Cr) and blood urea nitrogen (BUN) levels in rats. Further investigation revealed that the TFs markedly decreased the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) and intracellular reactive oxygen species (ROS), up-regulated the levels of silent information regulator factor 2-related enzyme 1 (Sirt1), nuclear factor erythroid 2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1), down-regulated the levels of Kelch like ECH-associated protein-1 (Keap1) and the nuclear translocation of nuclear factor-κBp65 (NF-κBp65), and decreased the mRNA levels of interleukine-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Furthermore, inhibiting Sirt1 by siRNA showed that the role of the natural product in protecting renal IRI was significantly attenuated, suggesting that the effect of the extract against renal IRI depended on Sirt1. Taken together, the TFs has significantly nephroprotective effect against IRI by affecting Sirt1/Nrf2/NF-κB signaling pathway, which should be developed as a new therapeutic agent or food additives to treat acute kidney injury in the future. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 8937 KiB

Open AccessArticle

Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine Based on 3D Tumor Models

by Hui Guo^1,2,3, Dongmei Liu^1,2,3, Bin Gao^2,3, Xiaohui Zhang^2,3, Minli You^2,3, Hui Ren^2,3, Hongbo Zhang^4,5, Hélder A. Santos⁴

and Feng Xu^2,3,6,*

¹ Department of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, China

² The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China

³ Bioinspired Engineering and Biomechanics Center (BEBC), Xi’an Jiaotong University, Xi’an 710049, China

⁴ Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland

⁵ School of Engineering and Applied Physics, Harvard University, Cambridge, MA 02138, USA

⁶ Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an 710049, China

Molecules 2016, 21(7), 954; https://doi.org/10.3390/molecules21070954 - 21 Jul 2016

Cited by 15 | Viewed by 8237

Abstract

Evodiamine (EVO) and rutaecarpine (RUT) are promising anti-tumor drug candidates. The evaluation of the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids of cancer cells would better recapitulate the native situation and thus better reflect an in vivo [...] Read more.

Evodiamine (EVO) and rutaecarpine (RUT) are promising anti-tumor drug candidates. The evaluation of the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids of cancer cells would better recapitulate the native situation and thus better reflect an in vivo response to the treatment. Herein, we employed the 3D culture of MCF-7 and SMMC-7721 cells based on hanging drop method and evaluated the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids, and compared the results with those obtained from 2D monolayers. The drugs’ IC₅₀ values were significantly increased from the range of 6.4–44.1 μM in 2D monolayers to 21.8–138.0 μM in 3D multicellular spheroids, which may be due to enhanced mass barrier and reduced drug penetration in 3D models. The fluorescence of EVO and RUT was measured via fluorescence spectroscopy and the cellular uptake of both drugs was characterized in 2D tumor models. The results showed that the cellular uptake concentrations of RUT increased with increasing drug concentrations. However, the EVO concentrations uptaken by the cells showed only a small change with increasing drug concentrations, which may be due to the different solubility of EVO and Rut in solvents. Overall, this study provided a new vision of the anti-tumor activity of EVO and RUT via 3D multicellular spheroids and cellular uptake through the fluorescence of compounds. Full article

(This article belongs to the Special Issue Drug Design and Discovery: Principles and Applications)

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10 pages, 1060 KiB

Open AccessArticle

Synthesis, Biological Evaluation and Molecular Modelling of 2′-Hydroxychalcones as Acetylcholinesterase Inhibitors

by Sri Devi Sukumaran¹, Chin Fei Chee^1,2, Geetha Viswanathan¹, Michael J. C. Buckle^1,*, Rozana Othman¹, Noorsaadah Abd. Rahman² and Lip Yong Chung^1,*

¹ Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia

² Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia

Molecules 2016, 21(7), 955; https://doi.org/10.3390/molecules21070955 - 22 Jul 2016

Cited by 29 | Viewed by 6502

Abstract

A series of 2′-hydroxy- and 2′-hydroxy-4′,6′-dimethoxychalcones was synthesised and evaluated as inhibitors of human acetylcholinesterase (AChE). The majority of the compounds were found to show some activity, with the most active compounds having IC₅₀ values of 40–85 µM. Higher activities were generally [...] Read more.

A series of 2′-hydroxy- and 2′-hydroxy-4′,6′-dimethoxychalcones was synthesised and evaluated as inhibitors of human acetylcholinesterase (AChE). The majority of the compounds were found to show some activity, with the most active compounds having IC₅₀ values of 40–85 µM. Higher activities were generally observed for compounds with methoxy substituents in the A ring and halogen substituents in the B ring. Kinetic studies on the most active compounds showed that they act as mixed-type inhibitors, in agreement with the results of molecular modelling studies, which suggested that they interact with residues in the peripheral anionic site and the gorge region of AChE. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 4483 KiB

Open AccessArticle

Qingxuan Jiangya Decoction Reverses Vascular Remodeling by Inducing Vascular Smooth Muscle Cell Apoptosis in Spontaneously Hypertensive Rats

by Fei Xiao^1,†

, Fei He^2,3,†, Hongwei Chen², Shan Lin⁴, Aling Shen², Youqin Chen⁵, Jianfeng Chu^2,* and Jun Peng^2,*

¹ College of Pharmacy, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Minhou Shangjie, Fuzhou 350122, Fujian, China

² Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Minhou Shangjie, Fuzhou 350122, Fujian, China

³ Fuqing Health and Family Planning Bureau, 23 Futang Road, Fuqing 350300, Fujian, China

⁴ Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Minhou Shangjie, Fuzhou 350122, Fujian, China

⁵ Case Western Reserve University School of Medicine, Rainbow Babies and Children’s Hospital, Cleveland, OH 44106, USA

^† These authors contributed equally to this work.

Molecules 2016, 21(7), 956; https://doi.org/10.3390/molecules21070956 - 22 Jul 2016

Cited by 19 | Viewed by 7702

Abstract

Qingxuan Jiangya Decoction (QXJYD), a traditional Chinese medicine formula prescribed by academician Ke-ji Chen, has been used in China to clinically treat hypertension for decades of years. However, the molecular mechanisms of its action remain largely unknown. In this study, we examined the [...] Read more.

Qingxuan Jiangya Decoction (QXJYD), a traditional Chinese medicine formula prescribed by academician Ke-ji Chen, has been used in China to clinically treat hypertension for decades of years. However, the molecular mechanisms of its action remain largely unknown. In this study, we examined the therapeutic efficacy of QXJYD against elevated systolic blood pressure in the spontaneously hypertensive rat (SHR) model, and investigated the underlying molecular mechanisms. We found that oral administration of QXJYD significantly reduced the elevation of systolic blood pressure in SHR but had no effect on body weight change. Additionally, QXJYD treatment significantly decreased the media thickness and ratio of media thickness/lumen diameter in the carotid arteries of SHR. Moreover, QXJYD remarkably promoted apoptosis of vascular smooth muscle cells and reduced the expression of anti-apoptotic B-cell leukemia/lymphoma 2. Furthermore, QXJYD significantly decreased the plasma Angiotensin II level in SHR. Collectively, our findings suggest that reversing vascular remodeling via inducing VSMC apoptosis could be one of the mechanisms whereby QXJYD treats hypertension. Full article

(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)

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15 pages, 1059 KiB

Open AccessArticle

New Isoxazolidine-Conjugates of Quinazolinones—Synthesis, Antiviral and Cytostatic Activity

by Dorota G. Piotrowska^1,*, Graciela Andrei², Dominique Schols², Robert Snoeck² and Magdalena Grabkowska-Drużyc¹

¹ Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland

² Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium

Molecules 2016, 21(7), 959; https://doi.org/10.3390/molecules21070959 - 22 Jul 2016

Cited by 21 | Viewed by 6761

Abstract

A novel series of (3-diethoxyphosphoryl)isoxazolidines substituted at C5 with various quinazolinones have been synthesized by the 1,3-dipolar cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone with N3-substitued 2-vinyl-3H-quinazolin-4-ones. All isoxazolidines were assessed for antiviral activity against a broad range of DNA and RNA viruses. [...] Read more.

A novel series of (3-diethoxyphosphoryl)isoxazolidines substituted at C5 with various quinazolinones have been synthesized by the 1,3-dipolar cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone with N3-substitued 2-vinyl-3H-quinazolin-4-ones. All isoxazolidines were assessed for antiviral activity against a broad range of DNA and RNA viruses. Isoxazolidines trans-11f/cis-11f (90:10), trans-11h and trans-11i/cis-11i (97:3) showed weak activity (EC₅₀ = 6.84, 15.29 and 9.44 μM) toward VZV (TK⁺ strain) which was only one order of magnitude lower than that of acyclovir used as a reference drug. Phosphonates trans-11b/cis-11b (90:10), trans-11c, trans-11e/cis-11e (90:10) and trans-11g appeared slightly active toward cytomegalovirus (EC₅₀ = 27–45 μM). Compounds containing benzyl substituents at N3 in the quinazolinone skeleton exhibited slight antiproliferative activity towards the tested immortalized cells with IC₅₀ in the 21–102 μM range. Full article

(This article belongs to the Section Medicinal Chemistry)

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9 pages, 585 KiB

Open AccessShort Note

Colour Evaluation, Bioactive Compound Content, Phenolic Acid Profiles and in Vitro Biological Activity of Passerina del Frusinate White Wines: Influence of Pre-Fermentative Skin Contact Times

by Katya Carbone^* and Luciano Fiordiponti

Consiglio per la ricerca in Agricoltura e l’Analisi dell’Economia Agraria—Fruit Tree Research Centre; Via di Fioranello, 52-00134 Rome, Italy

Molecules 2016, 21(7), 960; https://doi.org/10.3390/molecules21070960 - 22 Jul 2016

Cited by 8 | Viewed by 5900

Abstract

Passerina del Frusinate is an autochthonous wine grape variety, which grows in the Lazio region that is currently being evaluated by local wine producers. In this study, colour properties (CIELab coordinates), bioactive compounds (total polyphenols and flavan-3-ols), HPLC-DAD phenolic acid profiles and in [...] Read more.

Passerina del Frusinate is an autochthonous wine grape variety, which grows in the Lazio region that is currently being evaluated by local wine producers. In this study, colour properties (CIELab coordinates), bioactive compounds (total polyphenols and flavan-3-ols), HPLC-DAD phenolic acid profiles and in vitro biological activity of monovarietal Passerina del Frusinate white wines and the effect of different maceration times (0, 18 and 24 h) were evaluated based on these parameters. Results highlighted statistically significant differences for almost all analysed parameters due to a strong influence of the pre-fermentative skin contact time. The flavan content of macerated wines was six times higher than that of the control, while total polyphenols were 1.5 times higher. According to their phytochemical content, macerated wines showed the highest antiradical capacity tested by means of DPPH^• and ABTS^+• assays. Besides, prolonged maceration resulted in a reduction of CIELab coordinates as well as of the content of phenolic substances and antiradical capacity. Among the phenolic acids analysed, the most abundant were vanillic acid and caffeic acid; the latter proved to be the most susceptible to degradation as a result of prolonged maceration. Passerina del Frusinate appears as a phenol-rich white wine with a strong antioxidant potential similar to that of red wines. Full article

(This article belongs to the Collection Wine Chemistry)

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23 pages, 4053 KiB

Open AccessArticle

Chlorophyll a Covalently Bonded to Organo-Modified Translucent Silica Xerogels: Optimizing Fluorescence and Maximum Loading

by M. A. García-Sánchez^1,*, I. N. Serratos¹, R. Sosa², T. Tapia-Esquivel³, F. González-García³, F. Rojas-González¹, S. R. Tello-Solís¹, A. Y. Palacios-Enriquez¹, J. M. Esparza Schulz¹ and A. Arrieta⁴

¹ Department of Chemistry, Universidad Autónoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina, Ciudad de México 09340, Mexico

² Department of Physics, Universidad Autónoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina, Ciudad de México 09340, Mexico

³ Department of Process Engineering Hydraulic, Universidad Autónoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina, Ciudad de México 09340, Mexico

⁴ Department of Central Electron Microscopy Laboratory, Universidad Autónoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina, Ciudad de México 09340, Mexico

Molecules 2016, 21(7), 961; https://doi.org/10.3390/molecules21070961 - 22 Jul 2016

Cited by 8 | Viewed by 7091

Abstract

Chlorophyll is a pyrrolic pigment with important optical properties, which is the reason it has been studied for many years. Recently, interest has been rising with respect to this molecule because of its outstanding physicochemical properties, particularly applicable to the design and development [...] Read more.

Chlorophyll is a pyrrolic pigment with important optical properties, which is the reason it has been studied for many years. Recently, interest has been rising with respect to this molecule because of its outstanding physicochemical properties, particularly applicable to the design and development of luminescent materials, hybrid sensor systems, and photodynamic therapy devices for the treatment of cancer cells and bacteria. More recently, our research group has been finding evidence for the possibility of preserving these important properties of substrates containing chlorophyll covalently incorporated within solid pore matrices, such as SiO₂, TiO₂ or ZrO₂ synthesized through the sol-gel process. In this work, we study the optical properties of silica xerogels organo-modified on their surface with allyl and phenyl groups and containing different concentrations of chlorophyll bonded to the pore walls, in order to optimize the fluorescence that these macrocyclic species displays in solution. The intention of this investigation was to determine the maximum chlorophyll a concentration at which this molecule can be trapped inside the pores of a given xerogel and to ascertain if this pigment remains trapped as a monomer, a dimer, or aggregate. Allyl and phenyl groups were deposited on the surface of xerogels in view of their important effects on the stability of the molecule, as well as over the fluorescence emission of chlorophyll; however, these organic groups allow the trapping of either chlorophyll a monomers or dimers. The determination of the above parameters allows finding the most adequate systems for subsequent in vitro or in vivo studies. The characterization of the obtained xerogels was performed through spectroscopic absorption, emission and excitation spectra. These hybrid systems can be employed as mimics of natural systems; the entrapment of chlorophyll inside pore matrices indicates that it is possible to exploit some of the most physicochemical properties of trapped chlorophyll for diverse technological applications. The data herein collected suggest the possibility of applying the developed methodology to other active, captive molecules in order to synthesize new hybrid materials with optimized properties, suitable to be applied in diverse technological fields. Full article

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9 pages, 806 KiB

Open AccessArticle

Two New Pentacyclic Triterpene Saponins from the Leaves of Akebia trifoliata

by Qiao-Lin Xu^1,†, Jing Wang^2,3,†, Li-Mei Dong^2,4, Qiang Zhang^3,4, Bi Luo^3,4, Yong-Xia Jia^2,3, Hong-Feng Wang¹ and Jian-Wen Tan^2,3,*

¹ Guangdong Provincial Key Laboratory of Bio-Control for Forest Diseases and Pests, Guangdong Academy of Forestry, Guangzhou 510520, China

² Key Laboratory of Plant Resources Conservation and Sustainable Utilization, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, China

³ Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, China

⁴ College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China

^† These authors contributed equally to this work.

Molecules 2016, 21(7), 962; https://doi.org/10.3390/molecules21070962 - 22 Jul 2016

Cited by 20 | Viewed by 5663

Abstract

Two new pentacyclic triterpene saponins, named akebiaoside K (1) and akebiaoside N (2), were isolated from the leaves of Akebia trifoliata, together with five known triterpenoids 3–7. They were all isolated from the leaves of [...] Read more.

Two new pentacyclic triterpene saponins, named akebiaoside K (1) and akebiaoside N (2), were isolated from the leaves of Akebia trifoliata, together with five known triterpenoids 3–7. They were all isolated from the leaves of A. trifoliata for the first time. Their structures were established by spectral and chemical means. Triterpenes 5 and 7 were found to show moderate in vitro cytotoxicity against human tumor A549, HeLa and HepG2 cell lines, with IC₅₀ values ranging from 0.023 to 0.038 mM. Triterpenes 5–7 were further revealed to show significant in vitro α-glucosidase inhibitory activity with IC₅₀ values from 0.040 to 0.220 mM, making them more potent than the reference compound acarbose (IC₅₀ 0.409 mM). Meanwhile, no obvious inhibitory effects were observed for the isolated triterpene saponins 1–4 in both bioactivity assays. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 2080 KiB

Open AccessArticle

Synthesis, Characterization, and Retinol Stabilization of Fatty Amide-β-cyclodextrin Conjugates

by Hwanhee Kim¹, Yiluo Hu¹, Daham Jeong¹, Bong-Hyun Jun¹

, Eunae Cho^2,* and Seunho Jung^1,2,*

¹ Department of Bioscience and Biotechnology, Microbial Carbohydrate Resource Bank (MCRB), Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea

² Center for Biotechnology Research in UBITA (CBRU), Institute for Ubiquitous Information Technology and Applications (UBITA), Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea

Molecules 2016, 21(7), 963; https://doi.org/10.3390/molecules21070963 - 22 Jul 2016

Cited by 11 | Viewed by 8621

Abstract

Amphiphilic cyclodextrin (CD) has been the object of growing scientific attention because of its two recognition sites, the cavity and the apolar heart, formed by self-assembly. In the present study, mono[6-deoxy-6-(octadecanamido)]-β-CD and mono[6-deoxy-6-(octadecenamido)]-β-CD were successfully synthesized by reacting mono-6-amino-6-deoxy-β-CD with N-hydroxysuccinimide esters [...] Read more.

Amphiphilic cyclodextrin (CD) has been the object of growing scientific attention because of its two recognition sites, the cavity and the apolar heart, formed by self-assembly. In the present study, mono[6-deoxy-6-(octadecanamido)]-β-CD and mono[6-deoxy-6-(octadecenamido)]-β-CD were successfully synthesized by reacting mono-6-amino-6-deoxy-β-CD with N-hydroxysuccinimide esters of corresponding fatty acids in DMF. The structures were analyzed using nuclear magnetic resonance spectroscopy and mass spectrometry. The amphiphilic β-CDs were able to form self-assembled nano-vesicles in water, and the supramolecular architectures were characterized using fluorescence spectroscopy, dynamic light scattering, and transmission electron microscopy. Using the cavity-type nano-vesicles, all-trans-retinol was efficiently encapsulated; it was then stabilized against the photo-degradation. Therefore, the present fatty amide-β-CD conjugate will be a potential molecule for carrier systems in cosmetic and pharmaceutical applications. Full article

(This article belongs to the Special Issue Cyclodextrin Chemistry)

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Jump to: Editorial, Research, Other

15 pages, 2791 KiB

Open AccessReview

Targeting Bacterial Dsb Proteins for the Development of Anti-Virulence Agents

by Roxanne P. Smith¹, Jason J. Paxman¹, Martin J. Scanlon²

and Begoña Heras^1,*

¹ Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Kingsbury Drive, Bundoora, Vic 3083, Australia

² Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Royal Parade, Parkville, Vic 3052, Australia

Molecules 2016, 21(7), 811; https://doi.org/10.3390/molecules21070811 - 16 Jul 2016

Cited by 51 | Viewed by 10279

Abstract

Recent years have witnessed a dramatic increase in bacterial antimicrobial resistance and a decline in the development of novel antibiotics. New therapeutic strategies are urgently needed to combat the growing threat posed by multidrug resistant bacterial infections. The Dsb disulfide bond forming pathways [...] Read more.

Recent years have witnessed a dramatic increase in bacterial antimicrobial resistance and a decline in the development of novel antibiotics. New therapeutic strategies are urgently needed to combat the growing threat posed by multidrug resistant bacterial infections. The Dsb disulfide bond forming pathways are potential targets for the development of antimicrobial agents because they play a central role in bacterial pathogenesis. In particular, the DsbA/DsbB system catalyses disulfide bond formation in a wide array of virulence factors, which are essential for many pathogens to establish infections and cause disease. These redox enzymes are well placed as antimicrobial targets because they are taxonomically widespread, share low sequence identity with human proteins, and many years of basic research have provided a deep molecular understanding of these systems in bacteria. In this review, we discuss disulfide bond catalytic pathways in bacteria and their significance in pathogenesis. We also review the use of different approaches to develop inhibitors against Dsb proteins as potential anti-virulence agents, including fragment-based drug discovery, high-throughput screening and other structure-based drug discovery methods. Full article

(This article belongs to the Special Issue Developments in Fragment-Based Lead Discovery)

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20 pages, 1182 KiB

Open AccessReview

Justicidin B: A Promising Bioactive Lignan

by Shiva Hemmati^1,2,* and Hassan Seradj³

¹ Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, P. O. Box 71345-1583 Shiraz, Iran

² Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, P. O. Box 71345-3119 Shiraz, Iran

³ Department of Pharmacognosy, School of Pharmacy, Shiraz University of Medical Sciences, P. O. Box 71345-1583 Shiraz, Iran

Molecules 2016, 21(7), 820; https://doi.org/10.3390/molecules21070820 - 23 Jun 2016

Cited by 52 | Viewed by 9451

Abstract

Adverse effects and drug resistance to the current onchopharmacologicals have increased the demand for alternative novel therapeutics. We herein introduce justicidin B, an arylnaphthalen lignan isolated from different plant origins, especially Justicia, Phyllanthus, Haplophyllum and Linum species. This cyclolignan exhibits a [...] Read more.

Adverse effects and drug resistance to the current onchopharmacologicals have increased the demand for alternative novel therapeutics. We herein introduce justicidin B, an arylnaphthalen lignan isolated from different plant origins, especially Justicia, Phyllanthus, Haplophyllum and Linum species. This cyclolignan exhibits a wide array of biological properties ranges from piscicidal to antifungal, antiviral and antibacterial activities. Activity against Trypanosoma brucei makes justicidin B a potential antiprotozoal agent for the treatment of neglected tropical diseases. Pharmacological properties like antiplatelet, anti-inflammatory and bone resorption inhibition have been also attributed to justicidin B. This compound is a potent cytotoxic substance on several cell lines, especially chronic myeloid and chronic lymphoid leukemia. Pharmacological values, natural variation, as well as biotechnological production of justicidin B by plant cell, tissue and organ culture are also described in this review. Chemical characteristics and chromatographic methods to identify justicidin B and its biosynthetic pathway have been discussed. Different approaches to the total synthesis of justicidin B are compared. This review would shed light on the role of justicidin B as an intriguing natural compound and provides a chance to optimize conditions for industrial applications. Full article

(This article belongs to the Section Natural Products Chemistry)

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54 pages, 18909 KiB

Open AccessReview

Kazakh Ziziphora Species as Sources of Bioactive Substances

by Karel Šmejkal^1,*, Milan Malaník¹

, Karlygash Zhaparkulova²

, Zuriyadda Sakipova², Liliya Ibragimova², Galya Ibadullaeva² and Milan Žemlička³

¹ Department of Natural Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Brno 61242, Czech Republic

² Department of Pharmaceutical Technology, Faculty of Pharmacy, Kazakh National Medical University, Almaty 050000, Kazakhstan

³ Department of Pharmacognosy and Botany, The University of Veterinary Medicine and Pharmacy in Košice, Košice 04181, Slovakia

Molecules 2016, 21(7), 826; https://doi.org/10.3390/molecules21070826 - 25 Jun 2016

Cited by 30 | Viewed by 9949

Abstract

Ziziphora species represent the prototypical example of the Lamiaceae family. The phytochemicals present in Ziziphora include monoterpenic essential oils, triterpenes and phenolic substances belonging to the flavonoids. In Kazakh traditional medicine, Ziziphora species possess several medicinal uses. In particular, Z. bungeana Lam. and [...] Read more.

Ziziphora species represent the prototypical example of the Lamiaceae family. The phytochemicals present in Ziziphora include monoterpenic essential oils, triterpenes and phenolic substances belonging to the flavonoids. In Kazakh traditional medicine, Ziziphora species possess several medicinal uses. In particular, Z. bungeana Lam. and Z. clinopodioides Lam. are used for the treatment of illnesses related to the cardiovascular system or to combat different infections. Unfortunately, the majority of the information about the complex Ziziphora species is only available in Russian and Chinese language, therefore, we decided gather all available information on Kazakhstan Ziziphora, namely its content compounds, medicinal uses and published patents, to draw the attention of scientists to this very interesting plant with high medicinal potential. Full article

(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)

11 pages, 3400 KiB

Open AccessReview

Polymer-Supported Raney Nickel Catalysts for Sustainable Reduction Reactions

by Haibin Jiang, Shuliang Lu, Xiaohong Zhang, Wei Dai and Jinliang Qiao^*

SINOPEC Beijing Research Institute of Chemical Industry, Beijing 100013, China

Molecules 2016, 21(7), 833; https://doi.org/10.3390/molecules21070833 - 25 Jun 2016

Cited by 11 | Viewed by 9618

Abstract

Green is the future of chemistry. Catalysts with high selectivity are the key to green chemistry. Polymer-supported Raney catalysts have been found to have outstanding performance in the clean preparation of some chemicals. For example, a polyamide 6-supported Raney nickel catalyst provided a [...] Read more.

Green is the future of chemistry. Catalysts with high selectivity are the key to green chemistry. Polymer-supported Raney catalysts have been found to have outstanding performance in the clean preparation of some chemicals. For example, a polyamide 6-supported Raney nickel catalyst provided a 100.0% conversion of n-butyraldehyde without producing any detectable n-butyl ether, the main byproduct in industry, and eliminated the two main byproducts (isopropyl ether and methyl-iso-butylcarbinol) in the hydrogenation of acetone to isopropanol. Meanwhile, a model for how the polymer support brought about the elimination of byproducts is proposed and confirmed. In this account the preparation and applications of polymer-supported Raney catalysts along with the corresponding models will be reviewed. Full article

(This article belongs to the Special Issue Recent Advancements in Polymer-Supported Catalysis)

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10 pages, 492 KiB

Open AccessReview

The Effect of Capsaicin on Salivary Gland Dysfunction

by Yong-Hwan Shin, Jin Man Kim and Kyungpyo Park^*

Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Seoul 110-749, Korea

Molecules 2016, 21(7), 835; https://doi.org/10.3390/molecules21070835 - 25 Jun 2016

Cited by 27 | Viewed by 9885

Abstract

Capsaicin (trans-8-methyl-N-vanilyl-6-nonenamide) is a unique alkaloid isolated from hot chili peppers of the capsicum family. Capsaicin is an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), which is expressed in nociceptive sensory neurons and a range of secretory epithelia, including [...] Read more.

Capsaicin (trans-8-methyl-N-vanilyl-6-nonenamide) is a unique alkaloid isolated from hot chili peppers of the capsicum family. Capsaicin is an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), which is expressed in nociceptive sensory neurons and a range of secretory epithelia, including salivary glands. Capsaicin has analgesic and anti-inflammatory properties in sensory neurons. Recently, increasing evidence has indicated that capsaicin also affects saliva secretion and inflammation in salivary glands. Applying capsaicin increases salivary secretion in human and animal models. Capsaicin appears to increase salivation mainly by modulating the paracellular pathway in salivary glands. Capsaicin activates TRPV1, which modulates the permeability of tight junctions (TJ) by regulating the expression and function of putative intercellular adhesion molecules in an ERK (extracelluar signal-regulated kinase) -dependent manner. Capsaicin also improved dysfunction in transplanted salivary glands. Aside from the secretory effects of capsaicin, it has anti-inflammatory effects in salivary glands. The anti-inflammatory effect of capsaicin is, however, not mediated by TRPV1, but by inhibition of the NF-κB pathway. In conclusion, capsaicin might be a potential drug for alleviating dry mouth symptoms and inflammation of salivary glands. Full article

(This article belongs to the Special Issue Capsaicin)

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30 pages, 1358 KiB

Open AccessReview

Nanoparticles: Alternatives Against Drug-Resistant Pathogenic Microbes

by Gudepalya Renukaiah Rudramurthy¹

, Mallappa Kumara Swamy^2,*

, Uma Rani Sinniah^2,* and Ali Ghasemzadeh²

¹ Department of Biotechnology, East-West College of Science, Bangalore-560091, Karnataka, India

² Department of Crop Science, Faculty of Agriculture, Universiti Putra Malaysia, Serdang, Selangor, Darul Ehsan 43400, Malaysia

Molecules 2016, 21(7), 836; https://doi.org/10.3390/molecules21070836 - 27 Jun 2016

Cited by 470 | Viewed by 18568

Abstract

Antimicrobial substances may be synthetic, semisynthetic, or of natural origin (i.e., from plants and animals). Antimicrobials are considered “miracle drugs” and can determine if an infected patient/animal recovers or dies. However, the misuse of antimicrobials has led to the development of multi-drug-resistant bacteria, [...] Read more.

Antimicrobial substances may be synthetic, semisynthetic, or of natural origin (i.e., from plants and animals). Antimicrobials are considered “miracle drugs” and can determine if an infected patient/animal recovers or dies. However, the misuse of antimicrobials has led to the development of multi-drug-resistant bacteria, which is one of the greatest challenges for healthcare practitioners and is a significant global threat. The major concern with the development of antimicrobial resistance is the spread of resistant organisms. The replacement of conventional antimicrobials by new technology to counteract antimicrobial resistance is ongoing. Nanotechnology-driven innovations provide hope for patients and practitioners in overcoming the problem of drug resistance. Nanomaterials have tremendous potential in both the medical and veterinary fields. Several nanostructures comprising metallic particles have been developed to counteract microbial pathogens. The effectiveness of nanoparticles (NPs) depends on the interaction between the microorganism and the NPs. The development of effective nanomaterials requires in-depth knowledge of the physicochemical properties of NPs and the biological aspects of microorganisms. However, the risks associated with using NPs in healthcare need to be addressed. The present review highlights the antimicrobial effects of various nanomaterials and their potential advantages, drawbacks, or side effects. In addition, this comprehensive information may be useful in the discovery of broad-spectrum antimicrobial drugs for use against multi-drug-resistant microbial pathogens in the near future. Full article

(This article belongs to the Collection Nanomedicine)

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18 pages, 5318 KiB

Open AccessReview

Recent Advances in Interface Engineering for Planar Heterojunction Perovskite Solar Cells

by Wei Yin¹, Lijia Pan¹, Tingbin Yang^2,* and Yongye Liang²

¹ School of Electronic Science and Engineering, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China

² Department of Materials Science and Engineering, South University of Science and Technology of China, Shenzhen 518055, China

Molecules 2016, 21(7), 837; https://doi.org/10.3390/molecules21070837 - 25 Jun 2016

Cited by 28 | Viewed by 12925

Abstract

Organic-inorganic hybrid perovskite solar cells are considered as one of the most promising next-generation solar cells due to their advantages of low-cost precursors, high power conversion efficiency (PCE) and easy of processing. In the past few years, the PCEs have climbed from a [...] Read more.

Organic-inorganic hybrid perovskite solar cells are considered as one of the most promising next-generation solar cells due to their advantages of low-cost precursors, high power conversion efficiency (PCE) and easy of processing. In the past few years, the PCEs have climbed from a few to over 20% for perovskite solar cells. Recent developments demonstrate that perovskite exhibits ambipolar semiconducting characteristics, which allows for the construction of planar heterojunction (PHJ) perovskite solar cells. PHJ perovskite solar cells can avoid the use of high-temperature sintered mesoporous metal oxides, enabling simple processing and the fabrication of flexible and tandem perovskite solar cells. In planar heterojunction materials, hole/electron transport layers are introduced between a perovskite film and the anode/cathode. The hole and electron transporting layers are expected to enhance exciton separation, charge transportation and collection. Further, the supporting layer for the perovskite film not only plays an important role in energy-level alignment, but also affects perovskite film morphology, which have a great effect on device performance. In addition, interfacial layers also affect device stability. In this review, recent progress in interfacial engineering for PHJ perovskite solar cells will be reviewed, especially with the molecular interfacial materials. The supporting interfacial layers for the optimization of perovskite films will be systematically reviewed. Finally, the challenges remaining in perovskite solar cells research will be discussed. Full article

(This article belongs to the Special Issue Perovskite Solar Cells)

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33 pages, 1666 KiB

Open AccessReview

Capsaicin: Current Understanding of Its Mechanisms and Therapy of Pain and Other Pre-Clinical and Clinical Uses

by Victor Fattori^†

, Miriam S. N. Hohmann^†, Ana C. Rossaneis

, Felipe A. Pinho-Ribeiro and Waldiceu A. Verri^*

¹ Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid KM480 PR445, Caixa Postal 10.011, 86057-970 Londrina, Paraná, Brazil

^† These authors contributed equally to this paper.

Molecules 2016, 21(7), 844; https://doi.org/10.3390/molecules21070844 - 28 Jun 2016

Cited by 367 | Viewed by 66908

Abstract

In this review, we discuss the importance of capsaicin to the current understanding of neuronal modulation of pain and explore the mechanisms of capsaicin-induced pain. We will focus on the analgesic effects of capsaicin and its clinical applicability in treating pain. Furthermore, we [...] Read more.

In this review, we discuss the importance of capsaicin to the current understanding of neuronal modulation of pain and explore the mechanisms of capsaicin-induced pain. We will focus on the analgesic effects of capsaicin and its clinical applicability in treating pain. Furthermore, we will draw attention to the rationale for other clinical therapeutic uses and implications of capsaicin in diseases such as obesity, diabetes, cardiovascular conditions, cancer, airway diseases, itch, gastric, and urological disorders. Full article

(This article belongs to the Special Issue Capsaicin)

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14 pages, 2966 KiB

Open AccessReview

Process of Fragment-Based Lead Discovery—A Perspective from NMR

by Rongsheng Ma, Pengchao Wang, Jihui Wu and Ke Ruan^*

Hefei National Laboratory for Physical Science at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui, China

Molecules 2016, 21(7), 854; https://doi.org/10.3390/molecules21070854 - 16 Jul 2016

Cited by 25 | Viewed by 11154

Abstract

Fragment-based lead discovery (FBLD) has proven fruitful during the past two decades for a variety of targets, even challenging protein–protein interaction (PPI) systems. Nuclear magnetic resonance (NMR) spectroscopy plays a vital role, from initial fragment-based screening to lead generation, because of its power [...] Read more.

Fragment-based lead discovery (FBLD) has proven fruitful during the past two decades for a variety of targets, even challenging protein–protein interaction (PPI) systems. Nuclear magnetic resonance (NMR) spectroscopy plays a vital role, from initial fragment-based screening to lead generation, because of its power to probe the intrinsically weak interactions between targets and low-molecular-weight fragments. Here, we review the NMR FBLD process from initial library construction to lead generation. We describe technical aspects regarding fragment library design, ligand- and protein-observed screening, and protein–ligand structure model generation. For weak binders, the initial hit-to-lead evolution can be guided by structural information retrieved from NMR spectroscopy, including chemical shift perturbation, transferred pseudocontact shifts, and paramagnetic relaxation enhancement. This perspective examines structure-guided optimization from weak fragment screening hits to potent leads for challenging PPI targets. Full article

(This article belongs to the Special Issue Developments in Fragment-Based Lead Discovery)

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13 pages, 2504 KiB

Open AccessReview

Applications of ¹⁹F-NMR in Fragment-Based Drug Discovery

by Raymond S. Norton^*

, Eleanor W. W. Leung

, Indu R. Chandrashekaran

and Christopher A. MacRaild

Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Australia

Molecules 2016, 21(7), 860; https://doi.org/10.3390/molecules21070860 - 16 Jul 2016

Cited by 80 | Viewed by 12954

Abstract

¹⁹F-NMR has proved to be a valuable tool in fragment-based drug discovery. Its applications include screening libraries of fluorinated fragments, assessing competition among elaborated fragments and identifying the binding poses of promising hits. By observing fluorine in both the ligand and the [...] Read more.

¹⁹F-NMR has proved to be a valuable tool in fragment-based drug discovery. Its applications include screening libraries of fluorinated fragments, assessing competition among elaborated fragments and identifying the binding poses of promising hits. By observing fluorine in both the ligand and the target protein, useful information can be obtained on not only the binding pose but also the dynamics of ligand-protein interactions. These applications of ¹⁹F-NMR will be illustrated in this review with studies from our fragment-based drug discovery campaigns against protein targets in parasitic and infectious diseases. Full article

(This article belongs to the Special Issue Developments in Fragment-Based Lead Discovery)

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22 pages, 617 KiB

Open AccessReview

Advanced Nanobiomaterials: Vaccines, Diagnosis and Treatment of Infectious Diseases

by Eva Torres-Sangiao¹

, Alina Maria Holban^2,3 and Monica Cartelle Gestal^4,*

¹ Department of Microbiology and Parasitology, University Santiago de Compostela, Galicia 15782, Spain

² Department of Microbiology and Immunology, Faculty of Biology, University of Bucharest, Bucharest 060101, Romania

³ Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, Bucharest 060042, Romania

⁴ Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens (UGA), GA 30602, USA

Molecules 2016, 21(7), 867; https://doi.org/10.3390/molecules21070867 - 1 Jul 2016

Cited by 112 | Viewed by 12367

Abstract

The use of nanoparticles has contributed to many advances due to their important properties such as, size, shape or biocompatibility. The use of nanotechnology in medicine has great potential, especially in medical microbiology. Promising data show the possibility of shaping immune responses and [...] Read more.

The use of nanoparticles has contributed to many advances due to their important properties such as, size, shape or biocompatibility. The use of nanotechnology in medicine has great potential, especially in medical microbiology. Promising data show the possibility of shaping immune responses and fighting severe infections using synthetic materials. Different studies have suggested that the addition of synthetic nanoparticles in vaccines and immunotherapy will have a great impact on public health. On the other hand, antibiotic resistance is one of the major concerns worldwide; a recent report of the World Health Organization (WHO) states that antibiotic resistance could cause 300 million deaths by 2050. Nanomedicine offers an innovative tool for combating the high rates of resistance that we are fighting nowadays, by the development of both alternative therapeutic and prophylaxis approaches and also novel diagnosis methods. Early detection of infectious diseases is the key to a successful treatment and the new developed applications based on nanotechnology offer an increased sensibility and efficiency of the diagnosis. The aim of this review is to reveal and discuss the main advances made on the science of nanomaterials for the prevention, diagnosis and treatment of infectious diseases. Highlighting innovative approaches utilized to: (i) increasing the efficiency of vaccines; (ii) obtaining shuttle systems that require lower antibiotic concentrations; (iii) developing coating devices that inhibit microbial colonization and biofilm formation. Full article

(This article belongs to the Special Issue Nanobiostructures: Commemorative Issue in Honor of Professor Serban Solacolu (1905-1980) - Founder of the Romanian School of Oxide Materials Science and Engineering)

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15 pages, 7165 KiB

Open AccessReview

Doping-Promoted Solar Water Oxidation on Hematite Photoanodes

by Yuchao Zhang^1,2, Hongwei Ji^1,2, Wanhong Ma^1,2, Chuncheng Chen^1,2, Wenjing Song^1,2,* and Jincai Zhao^1,2,*

¹ Beijing National Laboratory for Molecular Sciences, Key Laboratory of Photochemistry, Institute of Chemistry, The Chinese Academy of Sciences, Beijing 100190, China

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

Molecules 2016, 21(7), 868; https://doi.org/10.3390/molecules21070868 - 1 Jul 2016

Cited by 28 | Viewed by 8874

Abstract

As one of the most promising materials for solar water oxidation, hematite has attracted intense research interest for four decades. Despite their desirable optical band gap, stability and other attractive features, there are great challenges for the implementation of hematite-based photoelectrochemical cells. In [...] Read more.

As one of the most promising materials for solar water oxidation, hematite has attracted intense research interest for four decades. Despite their desirable optical band gap, stability and other attractive features, there are great challenges for the implementation of hematite-based photoelectrochemical cells. In particular, the extremely low electron mobility leads to severe energy loss by electron hole recombination. Elemental doping, i.e., replacing lattice iron with foreign atoms, has been shown to be a practical solution. Here we review the significant progresses in metal and non-metal element doping-promoted hematite solar water oxidation, focusing on the role of dopants in adjusting carrier density, charge collection efficiency and surface water oxidation kinetics. The advantages and salient features of the different doping categories are compared and discussed. Full article

(This article belongs to the Special Issue Photocatalytic Water Splitting—the Untamed Dream)

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41 pages, 2245 KiB

Open AccessReview

New Perspectives on the Use of Phytochemicals as an Emergent Strategy to Control Bacterial Infections Including Biofilms

by Anabela Borges^1,2,3,*

, Ana Cristina Abreu^1,3

, Carla Dias^1,3, Maria José Saavedra³

, Fernanda Borges² and Manuel Simões^1,*

¹ LEPABE, Department of Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, s/n, Porto 4200-465, Portugal

² CIQUP, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Rua do Campo Alegre, s/n, Porto 4169-007, Portugal

³ CECAV-Veterinary and Animal Science Research Center, Department of Veterinary Science, University of Trás-os-Montes e Alto Douro, Apartado 1013, Vila Real 5001-801, Portugal

Molecules 2016, 21(7), 877; https://doi.org/10.3390/molecules21070877 - 5 Jul 2016

Cited by 217 | Viewed by 18839

Abstract

The majority of current infectious diseases are almost untreatable by conventional antibiotic therapy given the advent of multidrug-resistant bacteria. The degree of severity and the persistence of infections are worsened when microorganisms form biofilms. Therefore, efforts are being applied to develop new drugs [...] Read more.

The majority of current infectious diseases are almost untreatable by conventional antibiotic therapy given the advent of multidrug-resistant bacteria. The degree of severity and the persistence of infections are worsened when microorganisms form biofilms. Therefore, efforts are being applied to develop new drugs not as vulnerable as the current ones to bacterial resistance mechanisms, and also able to target bacteria in biofilms. Natural products, especially those obtained from plants, have proven to be outstanding compounds with unique properties, making them perfect candidates for these much-needed therapeutics. This review presents the current knowledge on the potentialities of plant products as antibiotic adjuvants to restore the therapeutic activity of drugs. Further, the difficulties associated with the use of the existing antibiotics in the treatment of biofilm-related infections are described. To counteract the biofilm resistance problems, innovative strategies are suggested based on literature data. Among the proposed strategies, the use of phytochemicals to inhibit or eradicate biofilms is highlighted. An overview on the use of phytochemicals to interfere with bacterial quorum sensing (QS) signaling pathways and underlying phenotypes is provided. The use of phytochemicals as chelating agents and efflux pump inhibitors is also reviewed. Full article

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

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11 pages, 3245 KiB

Open AccessReview

Radical Smiles Rearrangement: An Update

by Ingrid Allart-Simon, Stéphane Gérard^* and Janos Sapi^*

Institut de Chimie Moléculaire de Reims, UMR CNRS 7312, Université de Reims-Champagne-Ardenne, Faculté de Pharmacie, 51 rue Cognacq-Jay, F-51096 Reims Cedex, France

Molecules 2016, 21(7), 878; https://doi.org/10.3390/molecules21070878 - 6 Jul 2016

Cited by 85 | Viewed by 17976

Abstract

Over the decades the Smiles rearrangement and its variants have become essential synthetic tools in modern synthetic organic chemistry. In this mini-review we summarized some very recent results of the radical version of these rearrangements. The selected examples illustrate the synthetic power of [...] Read more.

Over the decades the Smiles rearrangement and its variants have become essential synthetic tools in modern synthetic organic chemistry. In this mini-review we summarized some very recent results of the radical version of these rearrangements. The selected examples illustrate the synthetic power of this approach, especially if it is incorporated into a domino process, for the preparation of polyfunctionalized complex molecules. Full article

(This article belongs to the Special Issue Free Radicals in Organic Synthesis)

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13 pages, 2480 KiB

Open AccessReview

Development of Droplet Microfluidics Enabling High-Throughput Single-Cell Analysis

by Na Wen¹, Zhan Zhao¹, Beiyuan Fan¹, Deyong Chen¹, Dong Men², Junbo Wang^1,* and Jian Chen^1,*

¹ Institute of Electronics, Chinese Academy of Sciences, Beijing 100190, China

² Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China

Molecules 2016, 21(7), 881; https://doi.org/10.3390/molecules21070881 - 5 Jul 2016

Cited by 88 | Viewed by 16645

Abstract

This article reviews recent developments in droplet microfluidics enabling high-throughput single-cell analysis. Five key aspects in this field are included in this review: (1) prototype demonstration of single-cell encapsulation in microfluidic droplets; (2) technical improvements of single-cell encapsulation in microfluidic droplets; (3) microfluidic [...] Read more.

This article reviews recent developments in droplet microfluidics enabling high-throughput single-cell analysis. Five key aspects in this field are included in this review: (1) prototype demonstration of single-cell encapsulation in microfluidic droplets; (2) technical improvements of single-cell encapsulation in microfluidic droplets; (3) microfluidic droplets enabling single-cell proteomic analysis; (4) microfluidic droplets enabling single-cell genomic analysis; and (5) integrated microfluidic droplet systems enabling single-cell screening. We examine the advantages and limitations of each technique and discuss future research opportunities by focusing on key performances of throughput, multifunctionality, and absolute quantification. Full article

(This article belongs to the Special Issue Micro/Nano Fluidics and Bio-MEMS)

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13 pages, 540 KiB

Open AccessReview

Precision or Personalized Medicine for Cancer Chemotherapy: Is there a Role for Herbal Medicine

by Zhijun Wang¹, Xuefeng Liu², Rebecca Lucinda Ka Yan Ho³, Christopher Wai Kei Lam^3,* and Moses Sing Sum Chow^1,*

¹ Center for Advancement of Drug Research and Evaluation, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA

² Department of Pathology and Center for Cell Reprogramming, Georgetown University Medical Center, Washington, DC 20057, USA

³ State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau, China

Molecules 2016, 21(7), 889; https://doi.org/10.3390/molecules21070889 - 7 Jul 2016

Cited by 24 | Viewed by 11042

Abstract

Although over 100 chemotherapeutic agents are currently available for the treatment of cancer patients, the overall long term clinical benefit is disappointing due to the lack of effectiveness or severe side effects from these agents. In order to improve the therapeutic outcome, a [...] Read more.

Although over 100 chemotherapeutic agents are currently available for the treatment of cancer patients, the overall long term clinical benefit is disappointing due to the lack of effectiveness or severe side effects from these agents. In order to improve the therapeutic outcome, a new approach called precision medicine or personalized medicine has been proposed and initiated by the U.S. National Institutes of Health. However, the limited availability of effective medications and the high cost are still the major barriers for many cancer patients. Thus alternative approaches such as herbal medicines could be a feasible and less costly option. Unfortunately, scientific evidence for the efficacy of a majority of herbal medicines is still lacking and their development to meet FDA approval or other regulatory agencies is a big challenge. However, herbal medicines may be able to play an important role in precision medicine or personalized medicine. This review will focus on the existing and future technologies that could speed the development of herbal products for treatment of resistant cancer in individual patients. Specifically, it will concentrate on reviewing the phenotypic (activity based) rather than genotypic (mechanism based) approach to develop herbal medicine useful for personalized cancer chemotherapy. Full article

(This article belongs to the Collection Herbal Medicine Research)

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51 pages, 8549 KiB

Open AccessReview

Marine Natural Products as Models to Circumvent Multidrug Resistance

by Solida Long¹

, Emília Sousa^1,2,*

, Anake Kijjoa^2,3

and Madalena M. M. Pinto^1,2

¹ Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Porto 4050-313, Portugal

² Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), Porto 4050-123, Portugal

³ Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto 4050-123, Portugal

Molecules 2016, 21(7), 892; https://doi.org/10.3390/molecules21070892 - 8 Jul 2016

Cited by 37 | Viewed by 10889

Abstract

Multidrug resistance (MDR) to anticancer drugs is a serious health problem that in many cases leads to cancer treatment failure. The ATP binding cassette (ABC) transporter P-glycoprotein (P-gp), which leads to premature efflux of drugs from cancer cells, is often responsible for MDR. [...] Read more.

Multidrug resistance (MDR) to anticancer drugs is a serious health problem that in many cases leads to cancer treatment failure. The ATP binding cassette (ABC) transporter P-glycoprotein (P-gp), which leads to premature efflux of drugs from cancer cells, is often responsible for MDR. On the other hand, a strategy to search for modulators from natural products to overcome MDR had been in place during the last decades. However, Nature limits the amount of some natural products, which has led to the development of synthetic strategies to increase their availability. This review summarizes the research findings on marine natural products and derivatives, mainly alkaloids, polyoxygenated sterols, polyketides, terpenoids, diketopiperazines, and peptides, with P-gp inhibitory activity highlighting the established structure-activity relationships. The synthetic pathways for the total synthesis of the most promising members and analogs are also presented. It is expected that the data gathered during the last decades concerning their synthesis and MDR-inhibiting activities will help medicinal chemists develop potential drug candidates using marine natural products as models which can deliver new ABC transporter inhibitor scaffolds. Full article

(This article belongs to the Special Issue New Approaches to Counteract Drug Resistance in Cancer)

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29 pages, 2222 KiB

Open AccessReview

Photocatalytic Water Splitting—The Untamed Dream: A Review of Recent Advances

by Tahereh Jafari¹, Ehsan Moharreri¹, Alireza Shirazi Amin², Ran Miao², Wenqiao Song² and Steven L. Suib^1,2,*

¹ Institute of Materials Science, University of Connecticut, 91 North Eagleville Road, Storrs, CT 06269-3222, USA

² Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, CT 06269-3060, USA

Molecules 2016, 21(7), 900; https://doi.org/10.3390/molecules21070900 - 9 Jul 2016

Cited by 524 | Viewed by 35770

Abstract

Photocatalytic water splitting using sunlight is a promising technology capable of providing high energy yield without pollutant byproducts. Herein, we review various aspects of this technology including chemical reactions, physiochemical conditions and photocatalyst types such as metal oxides, sulfides, nitrides, nanocomposites, and doped [...] Read more.

Photocatalytic water splitting using sunlight is a promising technology capable of providing high energy yield without pollutant byproducts. Herein, we review various aspects of this technology including chemical reactions, physiochemical conditions and photocatalyst types such as metal oxides, sulfides, nitrides, nanocomposites, and doped materials followed by recent advances in computational modeling of photoactive materials. As the best-known catalyst for photocatalytic hydrogen and oxygen evolution, TiO₂ is discussed in a separate section, along with its challenges such as the wide band gap, large overpotential for hydrogen evolution, and rapid recombination of produced electron-hole pairs. Various approaches are addressed to overcome these shortcomings, such as doping with different elements, heterojunction catalysts, noble metal deposition, and surface modification. Development of a photocatalytic corrosion resistant, visible light absorbing, defect-tuned material with small particle size is the key to complete the sunlight to hydrogen cycle efficiently. Computational studies have opened new avenues to understand and predict the electronic density of states and band structure of advanced materials and could pave the way for the rational design of efficient photocatalysts for water splitting. Future directions are focused on developing innovative junction architectures, novel synthesis methods and optimizing the existing active materials to enhance charge transfer, visible light absorption, reducing the gas evolution overpotential and maintaining chemical and physical stability. Full article

(This article belongs to the Special Issue Photocatalytic Water Splitting—the Untamed Dream)

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38 pages, 1411 KiB

Open AccessReview

Polyphenols: Extraction Methods, Antioxidative Action, Bioavailability and Anticarcinogenic Effects

by Eva Brglez Mojzer^1,†, Maša Knez Hrnčič^2,†, Mojca Škerget², Željko Knez^2,*

and Urban Bren^1,*

¹ Laboratory of Physical Chemistry and Chemical Thermodynamics, Faculty of Chemistry and Chemical Engineering, University of Maribor, Smetanova ulica 17, SI-2000 Maribor, Slovenia

² Laboratory of Separation Processes and Product Design, Faculty of Chemistry and Chemical Engineering, University of Maribor, Smetanova ulica 17, SI-2000 Maribor, Slovenia

^† These authors contributed equally to this work.

Molecules 2016, 21(7), 901; https://doi.org/10.3390/molecules21070901 - 11 Jul 2016

Cited by 739 | Viewed by 34836

Abstract

Being secondary plant metabolites, polyphenols represent a large and diverse group of substances abundantly present in a majority of fruits, herbs and vegetables. The current contribution is focused on their bioavailability, antioxidative and anticarcinogenic properties. An overview of extraction methods is also given, [...] Read more.

Being secondary plant metabolites, polyphenols represent a large and diverse group of substances abundantly present in a majority of fruits, herbs and vegetables. The current contribution is focused on their bioavailability, antioxidative and anticarcinogenic properties. An overview of extraction methods is also given, with supercritical fluid extraction highlighted as a promising eco-friendly alternative providing exceptional separation and protection from degradation of unstable polyphenols. The protective role of polyphenols against reactive oxygen and nitrogen species, UV light, plant pathogens, parasites and predators results in several beneficial biological activities giving rise to prophylaxis or possibly even to a cure for several prevailing human diseases, especially various cancer types. Omnipresence, specificity of the response and the absence of or low toxicity are crucial advantages of polyphenols as anticancer agents. The main problem represents their low bioavailability and rapid metabolism. One of the promising solutions lies in nanoformulation of polyphenols that prevents their degradation and thus enables significantly higher concentrations to reach the target cells. Another, more practiced, solution is the use of mixtures of various polyphenols that bring synergistic effects, resulting in lowering of the required therapeutic dose and in multitargeted action. The combination of polyphenols with existing drugs and therapies also shows promising results and significantly reduces their toxicity. Full article

(This article belongs to the Special Issue New Frontiers on the Metabolism, Bioavailability and Health Effects of Phenolic Compounds)

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18 pages, 3833 KiB

Open AccessReview

Protein-Directed Dynamic Combinatorial Chemistry: A Guide to Protein Ligand and Inhibitor Discovery

by Renjie Huang and Ivanhoe K. H. Leung^*

School of Chemical Sciences, The University of Auckland, Private Bag 92019, Victoria Street West, Auckland 1142, New Zealand

Molecules 2016, 21(7), 910; https://doi.org/10.3390/molecules21070910 - 16 Jul 2016

Cited by 37 | Viewed by 14754

Abstract

Protein-directed dynamic combinatorial chemistry is an emerging technique for efficient discovery of novel chemical structures for binding to a target protein. Typically, this method relies on a library of small molecules that react reversibly with each other to generate a combinatorial library. The [...] Read more.

Protein-directed dynamic combinatorial chemistry is an emerging technique for efficient discovery of novel chemical structures for binding to a target protein. Typically, this method relies on a library of small molecules that react reversibly with each other to generate a combinatorial library. The components in the combinatorial library are at equilibrium with each other under thermodynamic control. When a protein is added to the equilibrium mixture, and if the protein interacts with any components of the combinatorial library, the position of the equilibrium will shift and those components that interact with the protein will be amplified, which can then be identified by a suitable biophysical technique. Such information is useful as a starting point to guide further organic synthesis of novel protein ligands and enzyme inhibitors. This review uses literature examples to discuss the practicalities of applying this method to inhibitor discovery, in particular, the set-up of the combinatorial library, the reversible reactions that may be employed, and the choice of detection methods to screen protein ligands from a mixture of reversibly forming molecules. Full article

(This article belongs to the Special Issue Developments in Fragment-Based Lead Discovery)

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19 pages, 4993 KiB

Open AccessReview

Boron Nitride Nanotubes: Recent Advances in Their Synthesis, Functionalization, and Applications

by Chee Huei Lee¹, Shiva Bhandari², Bishnu Tiwari², Nazmiye Yapici², Dongyan Zhang² and Yoke Khin Yap^2,*

¹ Engineering Product Development, Singapore University of Technology and Design, 8 Somapah Road, Singapore 487372, Singapore

² Department of Physics, Michigan Technological University, 1400 Townsend Drive, Houghton, MI 49931, USA

Molecules 2016, 21(7), 922; https://doi.org/10.3390/molecules21070922 - 15 Jul 2016

Cited by 100 | Viewed by 15158

Abstract

A comprehensive overview of current research progress on boron nitride nanotubes (BNNTs) is presented in this article. Particularly, recent advancements in controlled synthesis and large-scale production of BNNTs will first be summarized. While recent success in mass production of BNNTs has opened up [...] Read more.

A comprehensive overview of current research progress on boron nitride nanotubes (BNNTs) is presented in this article. Particularly, recent advancements in controlled synthesis and large-scale production of BNNTs will first be summarized. While recent success in mass production of BNNTs has opened up new opportunities to implement the appealing properties in various applications, concerns about product purity and quality still remain. Secondly, we will summarize the progress in functionalization of BNNTs, which is the necessary step for their applications. Additionally, selected potential applications in structural composites and biomedicine will be highlighted. Full article

(This article belongs to the Special Issue Boron Nitride: Synthesis and Application)

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27 pages, 2768 KiB

Open AccessFeature PaperReview

Computational Approaches for the Discovery of Human Proteasome Inhibitors: An Overview

by Romina A. Guedes¹, Patrícia Serra¹

, Jorge A. R. Salvador^2,3 and Rita C. Guedes^1,*

¹ iMed.ULisboa, Research Institute for Medicines, Faculdade de Farmácia da Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal

² Laboratório de Química Farmacêutica, Faculdade de Farmácia da Universidade de Coimbra, Pólo das Ciências da Saúde-Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal

³ Center for Neurosciences and Cell Biology, Universidade de Coimbra, Rua Larga-Faculdade de Medicina, Pólo I, 3004-504 Coimbra, Portugal

Molecules 2016, 21(7), 927; https://doi.org/10.3390/molecules21070927 - 16 Jul 2016

Cited by 25 | Viewed by 10866

Abstract

Proteasome emerged as an important target in recent pharmacological research due to its pivotal role in degrading proteins in the cytoplasm and nucleus of eukaryotic cells, regulating a wide variety of cellular pathways, including cell growth and proliferation, apoptosis, DNA repair, transcription, immune [...] Read more.

Proteasome emerged as an important target in recent pharmacological research due to its pivotal role in degrading proteins in the cytoplasm and nucleus of eukaryotic cells, regulating a wide variety of cellular pathways, including cell growth and proliferation, apoptosis, DNA repair, transcription, immune response, and signaling processes. The last two decades witnessed intensive efforts to discover 20S proteasome inhibitors with significant chemical diversity and efficacy. To date, the US FDA approved to market three proteasome inhibitors: bortezomib, carfilzomib, and ixazomib. However new, safer and more efficient drugs are still required. Computer-aided drug discovery has long being used in drug discovery campaigns targeting the human proteasome. The aim of this review is to illustrate selected in silico methods like homology modeling, molecular docking, pharmacophore modeling, virtual screening, and combined methods that have been used in proteasome inhibitors discovery. Applications of these methods to proteasome inhibitors discovery will also be presented and discussed to raise improvements in this particular field. Full article

(This article belongs to the Special Issue Computational Design: A New Approach to Drug and Molecular Discovery)

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19 pages, 5183 KiB

Open AccessReview

A Novel Strategy for Biomass Upgrade: Cascade Approach to the Synthesis of Useful Compounds via C-C Bond Formation Using Biomass-Derived Sugars as Carbon Nucleophiles

by Sho Yamaguchi^* and Toshihide Baba

Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology, 4259-G1-14 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8502, Japan

Molecules 2016, 21(7), 937; https://doi.org/10.3390/molecules21070937 - 20 Jul 2016

Cited by 22 | Viewed by 8692

Abstract

Due to the depletion of fossil fuels, biomass-derived sugars have attracted increasing attention in recent years as an alternative carbon source. Although significant advances have been reported in the development of catalysts for the conversion of carbohydrates into key chemicals (e.g., degradation approaches [...] Read more.

Due to the depletion of fossil fuels, biomass-derived sugars have attracted increasing attention in recent years as an alternative carbon source. Although significant advances have been reported in the development of catalysts for the conversion of carbohydrates into key chemicals (e.g., degradation approaches based on the dehydration of hydroxyl groups or cleavage of C-C bonds via retro-aldol reactions), only a limited range of products can be obtained through such processes. Thus, the development of a novel and efficient strategy targeted towards the preparation of a range of compounds from biomass-derived sugars is required. We herein describe the highly-selective cascade syntheses of a range of useful compounds using biomass-derived sugars as carbon nucleophiles. We focus on the upgrade of C2 and C3 oxygenates generated from glucose to yield useful compounds via C-C bond formation. The establishment of this novel synthetic methodology to generate valuable chemical products from monosaccharides and their decomposed oxygenated materials renders carbohydrates a potential alternative carbon resource to fossil fuels. Full article

(This article belongs to the Special Issue Cascade Catalysis)

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16 pages, 243 KiB

Open AccessReview

Bioactivities and Health Benefits of Mushrooms Mainly from China

by Jiao-Jiao Zhang¹, Ya Li¹

, Tong Zhou¹, Dong-Ping Xu¹, Pei Zhang¹, Sha Li² and Hua-Bin Li^1,3,*

¹ Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China

² School of Chinese Medicine, The University of Hong Kong, Hong Kong 999077, China

³ South China Sea Bioresource Exploitation and Utilization Collaborative Innovation Center, Sun Yat-Sen University, Guangzhou 510006, China

Molecules 2016, 21(7), 938; https://doi.org/10.3390/molecules21070938 - 20 Jul 2016

Cited by 128 | Viewed by 21250

Abstract

Many mushrooms have been used as foods and medicines for a long time. Mushrooms contain polyphenols, polysaccharides, vitamins and minerals. Studies show that mushrooms possess various bioactivities, such as antioxidant, anti-inflammatory, anticancer, immunomodulatory, antimicrobial, hepatoprotective, and antidiabetic properties, therefore, mushrooms have attracted increasing [...] Read more.

Many mushrooms have been used as foods and medicines for a long time. Mushrooms contain polyphenols, polysaccharides, vitamins and minerals. Studies show that mushrooms possess various bioactivities, such as antioxidant, anti-inflammatory, anticancer, immunomodulatory, antimicrobial, hepatoprotective, and antidiabetic properties, therefore, mushrooms have attracted increasing attention in recent years, and could be developed into functional food or medicines for prevention and treatment of several chronic diseases, such as cancer, cardiovascular diseases, diabetes mellitus and neurodegenerative diseases. The present review summarizes the bioactivities and health benefits of mushrooms, and could be useful for full utilization of mushrooms. Full article

(This article belongs to the Section Natural Products Chemistry)

13 pages, 3806 KiB

Open AccessReview

Recent Advances in Substrate-Controlled Asymmetric Induction Derived from Chiral Pool α-Amino Acids for Natural Product Synthesis

by Seung-Mann Paek¹, Myeonggyo Jeong², Jeyun Jo², Yu Mi Heo¹, Young Taek Han³ and Hwayoung Yun^2,*

¹ College of Pharmacy, Research Institute of Pharmaceutical Science, Gyeongsang National University, Jinju daero, Jinju 52828, Korea

² College of Pharmacy, Pusan National University, Busan 46241, Korea

³ College of Pharmacy, Dankook University, Cheonan 31116, Korea

Molecules 2016, 21(7), 951; https://doi.org/10.3390/molecules21070951 - 21 Jul 2016

Cited by 46 | Viewed by 11724

Abstract

Chiral pool α-amino acids have been used as powerful tools for the total synthesis of structurally diverse natural products. Some common naturally occurring α-amino acids are readily available in both enantiomerically pure forms. The applications of the chiral pool in asymmetric synthesis can [...] Read more.

Chiral pool α-amino acids have been used as powerful tools for the total synthesis of structurally diverse natural products. Some common naturally occurring α-amino acids are readily available in both enantiomerically pure forms. The applications of the chiral pool in asymmetric synthesis can be categorized prudently as chiral sources, devices, and inducers. This review specifically examines recent advances in substrate-controlled asymmetric reactions induced by the chirality of α-amino acid templates in natural product synthesis research and related areas. Full article

(This article belongs to the Special Issue Synthesis of Bioactive Compounds from the Chiral Pool)

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15 pages, 4167 KiB

Open AccessReview

Metabolic Responses of Bacterial Cells to Immobilization

by Joanna Żur

, Danuta Wojcieszyńska and Urszula Guzik^*

Department of Biochemistry, Faculty of Biology and Environmental Protection, University of Silesia in Katowice, Jagiellonska 28, 40-032 Katowice, Poland

Molecules 2016, 21(7), 958; https://doi.org/10.3390/molecules21070958 - 22 Jul 2016

Cited by 168 | Viewed by 13371

Abstract

In recent years immobilized cells have commonly been used for various biotechnological applications, e.g., antibiotic production, soil bioremediation, biodegradation and biotransformation of xenobiotics in wastewater treatment plants. Although the literature data on the physiological changes and behaviour of cells in the immobilized state [...] Read more.

In recent years immobilized cells have commonly been used for various biotechnological applications, e.g., antibiotic production, soil bioremediation, biodegradation and biotransformation of xenobiotics in wastewater treatment plants. Although the literature data on the physiological changes and behaviour of cells in the immobilized state remain fragmentary, it is well documented that in natural settings microorganisms are mainly found in association with surfaces, which results in biofilm formation. Biofilms are characterized by genetic and physiological heterogeneity and the occurrence of altered microenvironments within the matrix. Microbial cells in communities display a variety of metabolic differences as compared to their free-living counterparts. Immobilization of bacteria can occur either as a natural phenomenon or as an artificial process. The majority of changes observed in immobilized cells result from protection provided by the supports. Knowledge about the main physiological responses occurring in immobilized cells may contribute to improving the efficiency of immobilization techniques. This paper reviews the main metabolic changes exhibited by immobilized bacterial cells, including growth rate, biodegradation capabilities, biocatalytic efficiency and plasmid stability. Full article

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40 pages, 6668 KiB

Open AccessReview

Immobilized Lignin Peroxidase-Like Metalloporphyrins as Reusable Catalysts in Oxidative Bleaching of Industrial Dyes

by Paolo Zucca^1,2

, Cláudia M. B. Neves³, Mário M. Q. Simões³

, Maria Da Graça P. M. S. Neves³

, Gianmarco Cocco¹ and Enrico Sanjust^1,*

¹ Dipartimento di Scienze Biomediche, Università di Cagliari, Complesso Universitario, SP1 Km 0.700, Monserrato (CA) 09042, Italy

² Consorzio UNO Oristano, via Carmine snc, Oristano 09170, Italy

³ Department of Chemistry and QOPNA, University of Aveiro, Aveiro 3810-193, Portugal

Molecules 2016, 21(7), 964; https://doi.org/10.3390/molecules21070964 - 22 Jul 2016

Cited by 53 | Viewed by 11324

Abstract

Synthetic and bioinspired metalloporphyrins are a class of redox-active catalysts able to emulate several enzymes such as cytochromes P450, ligninolytic peroxidases, and peroxygenases. Their ability to perform oxidation and degradation of recalcitrant compounds, including aliphatic hydrocarbons, phenolic and non-phenolic aromatic compounds, sulfides, and [...] Read more.

Synthetic and bioinspired metalloporphyrins are a class of redox-active catalysts able to emulate several enzymes such as cytochromes P450, ligninolytic peroxidases, and peroxygenases. Their ability to perform oxidation and degradation of recalcitrant compounds, including aliphatic hydrocarbons, phenolic and non-phenolic aromatic compounds, sulfides, and nitroso-compounds, has been deeply investigated. Such a broad substrate specificity has suggested their use also in the bleaching of textile plant wastewaters. In fact, industrial dyes belong to very different chemical classes, being their effective and inexpensive oxidation an important challenge from both economic and environmental perspective. Accordingly, we review here the most widespread synthetic metalloporphyrins, and the most promising formulations for large-scale applications. In particular, we focus on the most convenient approaches for immobilization to conceive economical affordable processes. Then, the molecular routes of catalysis and the reported substrate specificity on the treatment of the most diffused textile dyes are encompassed, including the use of redox mediators and the comparison with the most common biological and enzymatic alternative, in order to depict an updated picture of a very promising field for large-scale applications. Full article

(This article belongs to the Special Issue Tetrapyrrolic Macrocycles: Synthesis, Functionalization and Applications)

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15 pages, 648 KiB

Open AccessReview

Targeting Epithelial–Mesenchymal Transition (EMT) to Overcome Drug Resistance in Cancer

by Bowen Du and Joong Sup Shim^*

Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SAR 999078, China

Molecules 2016, 21(7), 965; https://doi.org/10.3390/molecules21070965 - 22 Jul 2016

Cited by 661 | Viewed by 32199

Abstract

Epithelial–mesenchymal transition (EMT) is known to play an important role in cancer progression, metastasis and drug resistance. Although there are controversies surrounding the causal relationship between EMT and cancer metastasis, the role of EMT in cancer drug resistance has been increasingly recognized. Numerous [...] Read more.

Epithelial–mesenchymal transition (EMT) is known to play an important role in cancer progression, metastasis and drug resistance. Although there are controversies surrounding the causal relationship between EMT and cancer metastasis, the role of EMT in cancer drug resistance has been increasingly recognized. Numerous EMT-related signaling pathways are involved in drug resistance in cancer cells. Cells undergoing EMT show a feature similar to cancer stem cells (CSCs), such as an increase in drug efflux pumps and anti-apoptotic effects. Therefore, targeting EMT has been considered a novel opportunity to overcome cancer drug resistance. This review describes the mechanism by which EMT contributes to drug resistance in cancer cells and summarizes new advances in research in EMT-associated drug resistance. Full article

(This article belongs to the Special Issue New Approaches to Counteract Drug Resistance in Cancer)

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1 pages, 146 KiB

Open AccessCorrection

Correction: Van der Merwe, J.D., et al. Short-Term and Sub-Chronic Dietary Exposure to Aspalathin-Enriched Green Rooibos (Aspalathus linearis) Extract Affects Rat Liver Function and Antioxidant Status. Molecules 2015, 20, 22674–22690

by Johanna Debora Van der Merwe¹, Dalene De Beer²

, Elizabeth Joubert^1,2

and Wentzel C. A. Gelderblom^3,4,*

¹ Department of Food Science, Stellenbosch University, Private Bag X1, Matieland (Stellenbosch) 7602, South Africa

² Post-Harvest and Wine Technology Division, Agricultural Research Council (ARC), Infruitec-Nietvoorbij, Private Bag X5026, Stellenbosch 7599, South Africa

³ Institute of Biomedical and Microbial Biotechnology, Cape Peninsula University of Technology, P.O. Box 1906, Bellville 7535, South Africa

⁴ Department of Biochemistry, Stellenbosch, Private Bag X1, Matieland (Stellenbosch) 7602, South Africa

Molecules 2016, 21(7), 907; https://doi.org/10.3390/molecules21070907 - 12 Jul 2016

Cited by 3 | Viewed by 4057

Abstract

The authors wish to make the following corrections to their published paper [1].[...] Full article

4 pages, 729 KiB

Open AccessCommentary

Solid-State Metalloproteins—An Alternative to Immobilisation

by Trevor D. Rapson

Commonwealth Scientific and Industrial Research Organisation (CSIRO), Black Mountain, Canberra, ACT 2601, Australia

Molecules 2016, 21(7), 919; https://doi.org/10.3390/molecules21070919 - 14 Jul 2016

Cited by 6 | Viewed by 4563

Abstract

This commentary outlines a protein engineering approach as an alternative to immobilisation developed in our laboratory. We use a recombinant silk protein into which metal active sites can be incorporated to produce solid-state metalloprotein materials. The silk protein directly coordinates to the metal [...] Read more.

This commentary outlines a protein engineering approach as an alternative to immobilisation developed in our laboratory. We use a recombinant silk protein into which metal active sites can be incorporated to produce solid-state metalloprotein materials. The silk protein directly coordinates to the metal centres providing control over their reactivity akin to that seen in naturally occurring metalloproteins. These solid-state materials are remarkably stable at a range of temperatures and different solvent conditions. I discuss the genesis of this approach and highlight areas where such solid-state materials could find application. Full article

(This article belongs to the Special Issue Enzyme Immobilization 2016)

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15 pages, 7623 KiB

Open AccessLetter

Carbon Nanotube Based Groundwater Remediation: The Case of Trichloroethylene

by Kshitij C. Jha^1,*, Zhuonan Liu¹, Hema Vijwani², Mallikarjuna Nadagouda², Sharmila M. Mukhopadhyay² and Mesfin Tsige^1,*

¹ Department of Polymer Science, The University of Akron, Akron, OH 44325, USA

² Center for Nanoscale Multifunctional Materials, Wright State University, Dayton, OH 45435, USA

Molecules 2016, 21(7), 953; https://doi.org/10.3390/molecules21070953 - 21 Jul 2016

Cited by 14 | Viewed by 8129

Abstract

Adsorption of chlorinated organic contaminants (COCs) on carbon nanotubes (CNTs) has been gaining ground as a remedial platform for groundwater treatment. Applications depend on our mechanistic understanding of COC adsorption on CNTs. This paper lays out the nature of competing interactions at play [...] Read more.

Adsorption of chlorinated organic contaminants (COCs) on carbon nanotubes (CNTs) has been gaining ground as a remedial platform for groundwater treatment. Applications depend on our mechanistic understanding of COC adsorption on CNTs. This paper lays out the nature of competing interactions at play in hybrid, membrane, and pure CNT based systems and presents results with the perspective of existing gaps in design strategies. First, current remediation approaches to trichloroethylene (TCE), the most ubiquitous of the COCs, is presented along with examination of forces contributing to adsorption of analogous contaminants at the molecular level. Second, we present results on TCE adsorption and remediation on pure and hybrid CNT systems with a stress on the specific nature of substrate and molecular architecture that would contribute to competitive adsorption. The delineation of intermolecular interactions that contribute to efficient remediation is needed for custom, scalable field design of purification systems for a wide range of contaminants. Full article

(This article belongs to the Special Issue Carbon Nanotubes: Advances and Applications)

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