Molecules

Editorial

2 pages, 161 KiB

Open AccessEditorial

Special Issue “Structure–Activity Relationship of Natural Products”

by Jean-Marc Sabatier

Laboratory INSERM UMR 1097, Aix-Marseille University, 163, Parc Scientifique et Technologique de Luminy, Avenue de Luminy, Bâtiment TPR2, Case 939, 13288 Marseille, France

Molecules 2017, 22(5), 697; https://doi.org/10.3390/molecules22050697 - 27 Apr 2017

Viewed by 3732

Abstract

This Special Issue of Molecules deals with the structure–activity relationship of natural compounds which possess some pharmacological/chemical properties of potential interest (from basic research to the clinical applications) in a wide range of areas, such as bacteriology, parasitology, cancerology, inflammation, etc.[...] Full article

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

7 pages, 184 KiB

Open AccessEditorial

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes

by Diego Muñoz-Torrero^1,*

, Arduino A. Mangoni²

, Catherine Guillou³

, Simona Collina⁴

, Jean Jacques Vanden Eynde⁵

, Jarkko Rautio⁶

, György M. Keserű⁷

, Christopher Hulme⁸, Kelly Chibale⁹, F. Javier Luque¹⁰

, Rafik Karaman^11,12

, Michael Gütschow¹³

, Hong Liu¹⁴ and Rino Ragno¹⁵

¹ Laboratory of Pharmaceutical Chemistry, Faculty of Pharmacy and Food Sciences, and Institute of Biomedicine (IBUB), University of Barcelona, Av. Joan XXIII; 27-31, E-08028 Barcelona, Spain

² Department of Clinical Pharmacology, Flinders University and Flinders Medical Centre, Bedford Park, SA 5042, Australia

³ Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université de Paris-Saclay, 91198 Gif-sur-Yvette, France

⁴ Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, Centre for Health Technologies (CHT), University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy

⁵ Organic Chemistry Laboratory, University of Mons-UMons, 7000 Mons, Belgium

⁶ School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.Box 1627, FI-70211 Kuopio, Finland

⁷ Medicinal Chemistry Research Group, Research Centre for Natural Sciences, The Hungarian Academy of Sciences, Magyar tudósok körútja 2, H-1117 Budapest, Hungary

⁸ Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ 85721, USA

⁹ Department of Chemistry, Institute of Infectious Disease and Molecular Medicine, and South African Medical Research Council Drug Discovery and Development Research Unit, University of Cape Town, Rondebosch 7701, South Africa

¹⁰ Department of Nutrition, Food Science, and Gastronomy and Institute of Biomedicine, University of Barcelona, Av. Prat de la Riba 171, 08921 Santa Coloma de Gramenet, Spain

¹¹ Pharmaceutical & Medicinal Chemistry Department, Faculty of Pharmacy, Al-Quds University, POB 20002 Jerusalem, Palestine

¹² Department of Sciences, University of Basilicata, Viadell’Ateneo Lucano 10, 85100 Potenza, Italy

¹³ Pharmaceutical Institute, University of Bonn, An der Immenburg 4, 53115 Bonn, Germany

¹⁴ Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China

¹⁵ Rome Center for Molecular Design, Department of Drug Chemistry and Technology, Sapienza University, P.le Aldo Moro 5, 00185 Rome, Italy

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Molecules 2017, 22(5), 743; https://doi.org/10.3390/molecules22050743 - 5 May 2017

Cited by 3 | Viewed by 7323

Abstract

The Editorial Board of the Medicinal Chemistry section of the journal Molecules publishes here its first Editorial, which has been prepared by highlighting, in sub-editorials of about one hundred words, some selected recently published articles that may have a profound impact on [...] Read more.

The Editorial Board of the Medicinal Chemistry section of the journal Molecules publishes here its first Editorial, which has been prepared by highlighting, in sub-editorials of about one hundred words, some selected recently published articles that may have a profound impact on drug discovery and therapy.[...] Full article

(This article belongs to the Collection Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes)

2 pages, 153 KiB

Open AccessEditorial

Special Issue: Ribozymes and RNA Catalysis

by Sabine Müller

Institut für Biochemie, Ernst-Moritz-Arndt-Universität Greifswald, Felix-Hausdorff-Str. 4, Greifswald 17489, Germany

Molecules 2017, 22(5), 789; https://doi.org/10.3390/molecules22050789 - 11 May 2017

Cited by 3 | Viewed by 4578

Abstract

Over the past 35 years, RNA has become a molecule of utmost interest for researchers in the life sciences. The many functions that RNA fulﬁlls in the cellular machinery have been elucidated with constant progress, revealing a complex network of RNA-mediated regulation of [...] Read more.

Over the past 35 years, RNA has become a molecule of utmost interest for researchers in the life sciences. The many functions that RNA fulﬁlls in the cellular machinery have been elucidated with constant progress, revealing a complex network of RNA-mediated regulation of key processes in the cellular life cycle [...]
Full article

(This article belongs to the Special Issue Ribozymes and RNA Catalysis)

Research

Jump to: Editorial, Review

14 pages, 920 KiB

Open AccessArticle

High-Throughput Determination of Sodium Danshensu in Beagle Dogs by the LCMS/MS Method, Employing Liquid-Liquid Extraction Based on 96-Well Format Plates

by Jingjing Jiang¹, Xin Zhao², Xiuxiu Li¹, Shengyuan Wu³, Shidan Yu¹, Yuefen Lou^4,* and Guorong Fan^1,3,5,*

¹ Shanghai Key Laboratory for Pharmaceutical Metabolite Research, School of Pharmacy, Second Military Medical University, Shanghai 200433, China

² Department of Pharmaceutical Analysis, School of Pharmacy, China Pharmaceutical University, No. 24 Tong Jia Xiang, Nanjing 210009, China

³ Laboratory of Drug Metabolism & Pharmacokinetics, School of Medicine, Tongji University, No. 1239 Siping Road, Shanghai 200092, China

⁴ Department of Pharmacy, Branch of Shanghai First People’s Hospital, Shanghai 200081, China

⁵ Department of Clinical Pharmacy, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, No. 100 Haining Road, Shanghai 200080, China

Molecules 2017, 22(5), 667; https://doi.org/10.3390/molecules22050667 - 25 Apr 2017

Cited by 13 | Viewed by 6948

Abstract

Sodium Danshensu (sodium d-(+)-β-(3,4-dihydroxyphenyl) lactate), one of the water-soluble ingredients in Salvia miltiorrhiza, exhibits potent relaxation of the coronary artery and anticoagulation effection. A high-throughput, rapid, and sensitive method combining liquid chromatography with electrospray ionization tandem mass spectrometry to determine the [...] Read more.

Sodium Danshensu (sodium d-(+)-β-(3,4-dihydroxyphenyl) lactate), one of the water-soluble ingredients in Salvia miltiorrhiza, exhibits potent relaxation of the coronary artery and anticoagulation effection. A high-throughput, rapid, and sensitive method combining liquid chromatography with electrospray ionization tandem mass spectrometry to determine the sodium danshensu in beagle dog plasma was developed and validated, using gallic acid as an internal standard (IS). Acidified plasma samples were extracted using 96-well liquid-liquid extraction, and were eluted on a CNW Athena C18 column (3 μm, 2.1 × 100 mm) by using a gradient mobile phase system of methanol and water (containing 0.2% formic acid). The mass spectrometric detection was achieved using negative ion electrospray ionization mode and monitoring the precursor→production combinations of m/z 197→135 for sodium danshensu and 169→125 for IS, in multiple reaction monitoring modes. Good linearity was achieved, and the linear range was 10–1000 ng/mL (R² > 0.996) with a quantification limit of 10 ng/mL for sodium danshensu in beagle dog plasma. The intra- and inter-day precision (RSD) ranged from 2.1% to 9.0%. The accuracy (RE) was between −8.6% and 5.7% at all quality control levels. The validated method was successfully applied to the pharmacokinetics study of sodium danshensu in beagle dog plasma after intravenous injection and oral administration of sodium danshensu. Full article

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15 pages, 3825 KiB

Open AccessArticle

Green Synthesis of Ag/Ag₂O Nanoparticles Using Aqueous Leaf Extract of Eupatorium odoratum and Its Antimicrobial and Mosquito Larvicidal Activities

by Elias E. Elemike^1,2,3, Damian C. Onwudiwe^1,2,*, Anthony C. Ekennia⁴

, Christopher U. Sonde⁴ and Richard C. Ehiri⁴

¹ Material Science Innovation and Modelling (MaSIM) Research Focus Area, Faculty of Agriculture, Science and Technology, North-West University (Mafikeng Campus), Private Bag X2046, Mmabatho 2357, South Africa

² Department of Chemistry, School of Mathematical and Physical Sciences, North-West University (Mafikeng Campus), Mmabatho 2735, South Africa

³ Department of Chemistry, College of Sciences, Federal University of Petroleum Resources Effurun, Delta State, Nigeria

⁴ Department of Chemistry, Federal University, Ndufu-Alike Ikwo (FUNAI), P.M.B. 1010, Abakaliki, Ebonyi State, Nigeria

Molecules 2017, 22(5), 674; https://doi.org/10.3390/molecules22050674 - 28 Apr 2017

Cited by 81 | Viewed by 9491

Abstract

The health challenges associated with pathogens and ectoparasites highlight the need for effective control approaches. Metal nanoparticles have been proposed as highly effective tools towards combatting different microbial organisms and parasites. The present work reports the antimicrobial and larvicidal potential of biosynthesized Ag/Ag [...] Read more.

The health challenges associated with pathogens and ectoparasites highlight the need for effective control approaches. Metal nanoparticles have been proposed as highly effective tools towards combatting different microbial organisms and parasites. The present work reports the antimicrobial and larvicidal potential of biosynthesized Ag/Ag₂O nanoparticles using aqueous leaf extract of Eupatorium odoratum (EO). The constituents of the leaf extract act as both reducing and stabilizing agents. The UV-VIS spectra of the nanoparticles showed surface plasmon resonance. The particle size and shape of the nanoparticles was analysed by transmission electron microscopy (TEM). The larvicidal study was carried out using third and fourth instar Culex quinquefasciatus larvae. The mosquito larvae were exposed to varying concentrations of plant extract (EO) and the synthesized nanoparticles, and their percentage of mortality was accounted for at different time intervals of 12 h and 24 h periods of exposure. The nanoparticles were more lethal against third and fourth instars of Culex quinquefasciatus larvae at the 24 h period of exposure with lower lethal concentration values (LC50 = 95.9 ppm; LC90 = 337.5 ppm) and (LC50 = 166.4 ppm; LC90 = 438.7 ppm) compared to the plant extract (LC50 = 396.8 ppm; LC90 = 716.8 ppm and LC50 = 448.3 ppm; LC90 = 803.9 ppm, respectively). The antimicrobial properties of the nanoparticles were established against different clinically-isolated microbial strains and compared to that of the plant extract (EO) and standard antimicrobial drugs. The nanoparticles were generally more active than the plant extract against the selected microbial organisms. The Gram-negative bacterial strains Escheerichua coli and Salmonella typhi were more susceptible towards the nanoparticles compared to the Gram-positive strains and the fungal organism. Full article

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

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11 pages, 2607 KiB

Open AccessArticle

Immune-Stimulatory Effects of Althaea rosea Flower Extracts through the MAPK Signaling Pathway in RAW264.7 Cells

by Yon-Suk Kim^1,2, Eun-Kyung Kim³

, Weligala Pahalagedara Amila Srilal Nawarathna¹, Xin Dong¹, Woen-Bin Shin¹, Jin-Su Park¹, Sang-Ho Moon² and Pyo-Jam Park^1,2,*

¹ Department of Biotechnology, Konkuk University, Chungju, Chungbuk 27478, Korea

² Nokyong Research Center, Konkuk University, Chungju, Chungbuk 27478, Korea

³ Division of Food and Bio Science, Konkuk University, Chungju 27478, Korea

Molecules 2017, 22(5), 679; https://doi.org/10.3390/molecules22050679 - 25 Apr 2017

Cited by 29 | Viewed by 7393

Abstract

Althaea rosea (Linn.) is a medicinal plant from China and Korea that has been traditionally used to control inflammation, to stop bedwetting and as a mouthwash in cases of bleeding gums. Its flowers are employed medicinally for their emollient, demulcent and diuretic properties, [...] Read more.

Althaea rosea (Linn.) is a medicinal plant from China and Korea that has been traditionally used to control inflammation, to stop bedwetting and as a mouthwash in cases of bleeding gums. Its flowers are employed medicinally for their emollient, demulcent and diuretic properties, which make them useful in chest complaints. Furthermore, a flower extract decoction is used to improve blood circulation, for the treatment of constipation, dysmenorrhoea, haemorrhages, etc. However, the possible mechanisms of the immune-stimulatory effect remains to be elucidated. Therefore, we investigated the role of Althaea rosea flower (ARF) extracts in the immune-stimulatory effect of macrophages and the underlying mechanisms of action. ARF water extract (ARFW) could dose-dependently increase NO production and cytokines (IL-6 and TNF-α). We also found that ARFW significantly increased the expression of iNOS and COX-2 proteins in RAW264.7 cells. Consistent with these results, MAPK protein (JNK, ERK, p38) expression levels were induced after treatment with ARFW. Additionally, ARFW showed a marked increase in the phosphorylation level of IκBα and subsequent IκBα degradation allowing NF-κB nuclear translocation. These results suggest that the immune-stimulatory effect of A. rosea flower extracts is mediated through the translocation of NF-κB p65 subunit into the nucleus from the cytoplasm and subsequent activation of pro-inflammatory cytokines (IL-6 and TNF-α) and other mediators (iNOS and COX-2), which occurs mainly through MAPK signalling pathway. Thus, we suggest that ARFW could be considered as a potential therapeutic agent useful in the development of immune-stimulatory compounds. Full article

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

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8 pages, 574 KiB

Open AccessArticle

Indole Derivatives Produced by the Metagenome Genes of the Escherichia coli-Harboring Marine Sponge Discodermia calyx

by Feng-Lou Liu¹ and Xiao-Long Yang^2,*

¹ Agricultural college, Ningxia University, Yinchuan 750021, Ningxia, China

² Innovative Drug Research Centre (IDRC), School of Pharmaceutical Sciences, Huxi Campus, Chongqing University, Chongqing 401331, China

Molecules 2017, 22(5), 681; https://doi.org/10.3390/molecules22050681 - 25 Apr 2017

Cited by 6 | Viewed by 4463

Abstract

Three indole derivatives, a novel benzoxazine-indole hybrid (1) and two known indole trimers (2, 3), were isolated from the metagenomic library of the marine sponge Discodermia calyx based on functional screening. Their structures were elucidated by extensive spectroscopic [...] Read more.

Three indole derivatives, a novel benzoxazine-indole hybrid (1) and two known indole trimers (2, 3), were isolated from the metagenomic library of the marine sponge Discodermia calyx based on functional screening. Their structures were elucidated by extensive spectroscopic analysis and comparison of their NMR data to that of known compounds. The antibacterial assay indicated that only compound 2 displayed significant antibacterial activity against Bacillus cereus, with approximately 20 mm diameter growth inhibition at 10 µg/paper. HPLC analyses revealed that compound 2 is a newly induced metabolite, and the concentration of 3 was obviously enhanced in contrast to negative control, while 1 was not detected, allowing us to predict that the formation of 2 might be induced by exogenous genes derived from the sponge metagenome, whereas compound 1 could be formed through a non-enzymatic process during the isolation procedure. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 5467 KiB

Open AccessArticle

Xanthones from the Pericarp of Garcinia mangostana

by Renyue Yang^1,†, Ping Li^1,†, Nana Li¹, Qian Zhang¹, Xue Bai¹, Lishuo Wang¹, Yiying Xiao¹, Lirong Sun^2,*, Quan Yang^3,* and Jian Yan^1,*

¹ Key Laboratory of Tropical Agro Environment, Ministry of Agriculture and Guangdong Engineering Research Centre for Modern Eco-Agriculture, South China Agricultural University, Guangzhou 510642, China

² Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China

³ Laboratory of State Administration of Traditional Chinese Medicine for Production and Development of Cantonese Medicinal Materials, School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China

^† These authors contributed equally to this work.

Molecules 2017, 22(5), 683; https://doi.org/10.3390/molecules22050683 - 25 Apr 2017

Cited by 46 | Viewed by 11943

Abstract

Mangosteen (Garcinia mangostana L.) is one of the most popular tropical fruits (called the “Queen of Fruits”), and is a rich source of oxygenated and prenylated xanthone derivatives. In the present work, phytochemical investigation has resulted in one new prenylated xanthone and [...] Read more.

Mangosteen (Garcinia mangostana L.) is one of the most popular tropical fruits (called the “Queen of Fruits”), and is a rich source of oxygenated and prenylated xanthone derivatives. In the present work, phytochemical investigation has resulted in one new prenylated xanthone and 13 known xanthones isolated from the pericarp of G. mangostana. Their structures were established by spectroscopic data analysis, including X-ray diffraction. The new one was further tested for cytotoxic activity against seven cancer cell lines (CNE-1, CNE-2, A549, H490, PC-3, SGC-7901, U87), displaying the half maximal inhibitory concentration (IC₅₀) values 3.35, 4.01, 4.84, 7.84, 6.21, 8.09, and 6.39 μM, respectively. It is noteworthy that the new compound can promote CNE-2 cells apoptosis in late stage, having a remarkable inhibition effect on the side population growth of CNE-2 at 1.26 μM. The bioactive compound was also detected in extract from fresh mangosteen flesh, which indicated that the popular fruit could have potential cytotoxic activity for cancer cell lines. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 1356 KiB

Open AccessArticle

C-C Coupling Reactions between Benzofurazan Derivatives and 1,3-Diaminobenzenes

by Gabriele Micheletti^1,*

, Silvia Bordoni¹, Elena Chugunova² and Carla Boga^1,*

¹ Department of Industrial Chemistry ‘Toso Montanari’, Alma Mater Studiorum Università di Bologna Viale Del Risorgimento, Bologna 4402136, Italy

² A.E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, Akad. Arbuzov st. 8, Kazan, Tatarstan 420088, Russia

Molecules 2017, 22(5), 684; https://doi.org/10.3390/molecules22050684 - 26 Apr 2017

Cited by 6 | Viewed by 6399

Abstract

Aromatic substitution reactions between 1,3-diaminobenzene and chloronitrobenzofurazan derivatives have never been reported so far. The aim of the current study was to synthesize novel electron-donor and -acceptor architectures of interest in applied fields and to provide new insights on the nucleophilic behavior of [...] Read more.

Aromatic substitution reactions between 1,3-diaminobenzene and chloronitrobenzofurazan derivatives have never been reported so far. The aim of the current study was to synthesize novel electron-donor and -acceptor architectures of interest in applied fields and to provide new insights on the nucleophilic behavior of 1,3-diaminobenzenes. The reaction of 1,3-dipiperidinyl-, 1,3-dimorpholinyl-, 1,3-dipyrrolidinyl-, or 1,3-dimethylamino-benzene with 7-chloro-4,6-dinitrobenzofuroxan or with a series of chloro-nitrobenzofurazans has been carried out in mild conditions. The partners reactivity has been investigated by monitoring the reaction course through ¹H-NMR spectroscopy. The reaction occurred in a regioselective way, providing in good yields the novel C-C coupling compounds. Indications on the reactivity behavior for the studied nucleophiles have been relieved. Full article

(This article belongs to the Special Issue Women in Organic Chemistry)

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12 pages, 2557 KiB

Open AccessArticle

Investigation of the Anti-Leishmania (Leishmania) infantum Activity of Some Natural Sesquiterpene Lactones

by Imke F. Wulsten¹, Thais A. Costa-Silva², Juliana T. Mesquita², Marta L. Lima^2,3, Mariana K. Galuppo², Noemi N. Taniwaki², Samanta E. T. Borborema², Fernando B. Da Costa⁴

, Thomas J. Schmidt^5,*

and Andre G. Tempone^2,*

¹ Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin, 14195 Berlin, Germany

² Centre for Parasitology and Mycology, Instituto Adolfo Lutz (IAL), Av. Dr. Arnaldo, 351, CEP 01246-900 São Paulo, SP, Brazil

³ Instituto de Medicina Tropical, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470, CEP 05403-000 São Paulo, SP, Brazil

⁴ AsterBioChem Research Team, Laboratory of Pharmacognosy, School of Pharmaceutical Sciences of Ribeirão Preto, USP, Av. do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil

⁵ Institute of Pharmaceutical Biology and Phytochemistry (IPBP), University of Münster, PharmaCampus, Corrensstraße 48, 48149 Münster, Germany

Molecules 2017, 22(5), 685; https://doi.org/10.3390/molecules22050685 - 25 Apr 2017

Cited by 23 | Viewed by 7187

Abstract

Leishmaniases are neglected infectious diseases caused by parasites of the ‘protozoan’ genus Leishmania. Depending on the parasite species, different clinical forms are known as cutaneous, muco-cutaneous, and the visceral leishmaniasis (VL). VL is particularly fatal and the therapy presents limitations. In the [...] Read more.

Leishmaniases are neglected infectious diseases caused by parasites of the ‘protozoan’ genus Leishmania. Depending on the parasite species, different clinical forms are known as cutaneous, muco-cutaneous, and the visceral leishmaniasis (VL). VL is particularly fatal and the therapy presents limitations. In the search for new anti-leishmanial hit compounds, seven natural sesquiterpene lactones were evaluated against promastigotes and intracellular amastigotes of Leishmania (Leishmania) infantum, a pathogen causing VL. The pseudoguaianolides mexicanin I and helenalin acetate demonstrated the highest selectivity and potency against intracellular amastigotes. In addition, promastigotes treated with helenalin acetate were subject to an ultrastructural and biochemical investigation. The lethal action of the compound was investigated by fluorescence-activated cell sorting and related techniques to detect alterations in reactive oxygen species (ROS) content, plasma membrane permeability, and mitochondrial membrane potential. Helenalin acetate significantly reduced the mitochondrial membrane potential and the mitochondrial structural damage was also confirmed by transmission electron microscopy, displaying an intense organelle swelling. No alteration of plasma membrane permeability or ROS content could be detected. Additionally, helenalin acetate significantly increased the production of nitric oxide in peritoneal macrophages, probably potentiating the activity against the intracellular amastigotes. Helenalin acetate could hence be a useful anti-leishmanial scaffold for further optimization studies. Full article

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

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14 pages, 1625 KiB

Open AccessArticle

Relationship between Expression of Chalcone Synthase Genes and Chromones in Artificial Agarwood induced by Formic Acid Stimulation Combined with Fusarium sp. A2 Inoculation

by Xiaodong Chen^1,2,3

, Xiaoling Zhu², Meirou Feng², Zhaojian Zhong², Xin Zhou², Xiaoying Chen², Wei Ye¹, Weimin Zhang^1,* and Xiaoxia Gao^1,2,*

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

² School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China

³ Sirio Pharma Co., Ltd., Shantou 515041, China

Molecules 2017, 22(5), 686; https://doi.org/10.3390/molecules22050686 - 25 Apr 2017

Cited by 19 | Viewed by 4647

Abstract

Agarwood (gaharu) is a fragrant resin produced in the heartwood of resinous Gyrinops and Aquilaria species. Artificial agarwood samples were obtained from Aquilaria sinensis (Lour.) Gilg using formic acid (FA) stimulation combined with Fusarium sp. A2 inoculation. The relationship between the expression of [...] Read more.

Agarwood (gaharu) is a fragrant resin produced in the heartwood of resinous Gyrinops and Aquilaria species. Artificial agarwood samples were obtained from Aquilaria sinensis (Lour.) Gilg using formic acid (FA) stimulation combined with Fusarium sp. A2 inoculation. The relationship between the expression of chalcone synthase genes (CHS) and dynamic changes in chromone content was explored in resin-deposited parts of the trunks of A. sinensis. CHS gene expression levels were detected by qRT-PCR analysis. The chemical composition of agarwood obtained from the heartwood of A. sinensis before and within 1 year after induction was determined by GC-MS. After induction with FA stimulation combined with F. sp. A2 inoculation, the CHS1 gene showed relatively high expression, whereas the CHS2 gene showed low expression. The relative gene expression level of CHS1 peaked at 12 months, with a 153.1-fold increase, and the dominant period of the CHS2 gene expression was 10 months with a 14.13-fold increase. Moreover, chromones were not detected until after 2 months, and a large proportion of chromone compounds were detected after 4 months. Chromone content increased with time and peaked at 12 months. CHS1 gene expression was significantly correlated with 6-hydroxy-2-(2-phenylethyl)chromone accumulation, and CHS2 gene expression was significantly correlated with 5-hydroxy-6-methoxy-2-(2-phenylethyl)chromone accumulation. CHS gene expression was extremely sensitive to FA stimulation combined with F. sp. A2 inoculation and responded to late-onset injury. CHS genes expression also preceded the chromone accumulation. This work laid the foundation for studies on the mechanism by which genes regulate chromone biosynthesis pathways during the formation of agarwood resin in A. sinensis. Full article

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13 pages, 879 KiB

Open AccessArticle

Synthesis and Bioactivity Evaluation of Novel 2-Salicyloylbenzofurans as Antibacterial Agents

by Phuong-Thuy T. Phan^1,*, Thu-Trang T. Nguyen^2,3, Hong-Nhung T. Nguyen³, Bao-Khanh N. Le³, Thao T. Vu⁴, Dong C. Tran⁴ and Tuan-Anh N. Pham^3,*

¹ Department of Medicinal Chemistry, Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam

² Department of Pharmaceutics, Faculty of Pharmacy, Da Nang University of Medical Technology and Pharmacy, Da Nang 550000, Vietnam

³ Department of Organic Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 700000, Vietnam

⁴ Department of Microbiology and Parasitology, Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 700000, Vietnam

Molecules 2017, 22(5), 687; https://doi.org/10.3390/molecules22050687 - 25 Apr 2017

Cited by 17 | Viewed by 7428

Abstract

In order to discover new antibacterial agents, series of 2-salicyloylbenzofuran derivatives were designed, synthesized and evaluated for their antibacterial activities against three Gram-(+) strains (methicillin-sensitive Staphylococcus aureus (MSSA) ATCC 29213, methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, and Streptococcus faecalis (S. faecalis) [...] Read more.

In order to discover new antibacterial agents, series of 2-salicyloylbenzofuran derivatives were designed, synthesized and evaluated for their antibacterial activities against three Gram-(+) strains (methicillin-sensitive Staphylococcus aureus (MSSA) ATCC 29213, methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, and Streptococcus faecalis (S. faecalis) ATCC 29212) and one Gram-(−) strain (Escherichia coli (E. coli) ATCC 25922). The 2-salicyloylbenzofuran heterocycles were generated by Rap–Stoermer condensation of salicylaldehydes with phenacyl bromides and then converted to diverse O-ether derivatives by Williamson synthesis. The targeted products were screened for in vitro qualitative (zone of inhibition) and quantitative (MIC) antibacterial activities by agar well diffusion assay and agar dilution method. Amongst the compounds, those bearing carboxylic acid functional group were found to exhibit reasonable activity against Gram-(+) bacterial strains including S. faecalis, MSSA and MRSA with the most potent antibacterial agent 8h (MICs = 0.06–0.12 mM). Besides, the 2-salicyloylbenzofurans partly displayed inhibitory activity against MRSA with the best MICs = 0.14 mM (8f) and 0.12 mM (8h). Finally, the antibacterial results preliminarily suggested that the substituent bearing carboxylic acid group at salicyloyl-C2 and the bromine atoms on the benzofuran moiety seem to be the functionality necessary for antibacterial activities. Full article

(This article belongs to the Section Medicinal Chemistry)

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9 pages, 1997 KiB

Open AccessArticle

Anthocyanin Profiles in Flowers of Grape Hyacinth

by Qian Lou^1,2,3,†, Lin Wang^2,3,4,†, Hongli Liu^2,3,4 and Yali Liu^2,3,4,*

¹ College of Horticulture, Northwest A & F University, Yangling 712100, Shaanxi, China

² Key Laboratory of Biology and Genetic Improvement of Horticultural Crops (Northwest Region), Ministry of Agriculture, Yangling 712100, Shaanxi, China

³ State Key Laboratory of Crop Stress Biology in Arid Areas, Northwest A&F University, Yangling 712100, Shaanxi, China

⁴ College of Landscape Architecture and Arts, Northwest A & F University, Yangling 712100, Shaanxi, China

^† The first two authors contributed equally to this research.

Molecules 2017, 22(5), 688; https://doi.org/10.3390/molecules22050688 - 26 Apr 2017

Cited by 30 | Viewed by 8868

Abstract

Grape hyacinth (Muscari spp.) is a popular ornamental bulbous perennial famous for its blue flowers. To understand the chemical basis of the rich blue colors in this plant, anthocyanin profiles of six blue flowering grape hyacinths as well as one pink and [...] Read more.

Grape hyacinth (Muscari spp.) is a popular ornamental bulbous perennial famous for its blue flowers. To understand the chemical basis of the rich blue colors in this plant, anthocyanin profiles of six blue flowering grape hyacinths as well as one pink and one white cultivar were determined using high-performance liquid chromatography and mass spectrometry. Along with two known compounds, eight putative anthocyanins were identified in the tepals of grape hyacinth for the first time. The accumulation and distribution of anthocyanins in the plant showed significant cultivar and flower development specificity. Violet-blue flowers mainly contained simple delphinidin-type anthocyanins bearing one or two methyl-groups but no acyl groups, whereas white and pink flowers synthesised more complex pelargonidin/cyanidin-derivatives with acyl-moieties but no methyl-groups. The results partially reveal why solid blue, orange or red flowers are rare in this plant in nature. In addition, pelargonidin-type anthocyanins were found for the first time in the genus, bringing more opportunities in terms of breeding of flower color in grape hyacinth. Full article

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

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14 pages, 3514 KiB

Open AccessArticle

Application of UHPLC-ESI-Q-TOF-MS to Identify Multiple Constituents in Processed Products of the Herbal Medicine Ligustri Lucidi Fructus

by Hui Li, Weifeng Yao^*, Qinan Liu, Jia Xu, Beihua Bao

, Mingqiu Shan

, Yudan Cao, Fangfang Cheng, Anwei Ding and Li Zhang^*

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and State Key Laboratory Cultivation Base for TCM Quality and Efficacy, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China

Molecules 2017, 22(5), 689; https://doi.org/10.3390/molecules22050689 - 26 Apr 2017

Cited by 83 | Viewed by 9469

Abstract

Ligustri Lucidi Fructus (LLF), the fruit of Ligustrum lucidum Ait. (Oleaceae), has been used as a common herbal medicine in clinical practice in China for nearly 2000 years. In most cases, LLF is prescribed in decoctions in the form of processed products rather [...] Read more.

Ligustri Lucidi Fructus (LLF), the fruit of Ligustrum lucidum Ait. (Oleaceae), has been used as a common herbal medicine in clinical practice in China for nearly 2000 years. In most cases, LLF is prescribed in decoctions in the form of processed products rather than crude drugs. In this study, an ultra-high performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-ESI-Q-TOF-MS) method was established for rapid separation and identification of multiple constituents in the 80% methanol extract of processed-LLF. A total of 50 compounds (one phenylethanoid, seven phenylethanoid glycosides, seven flavonoids, 25 iridoids, nine triterpenoids and one cyclohexanecarboxylic acid) were either unambiguously identified or tentatively characterized with the aid of authentic standards or published data. Luteolin-7-O-rutinoside, oleoside and secologanoside were detected in LLF for the first time. This study enriches the chemical profiling of processed-LLF and could provide valuable information for the quality control and further investigation of processed-LLF and crude LLF. Full article

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13 pages, 1787 KiB

Open AccessArticle

Discovery of Farnesoid X Receptor Antagonists Based on a Library of Oleanolic Acid 3-O-Esters through Diverse Substituent Design and Molecular Docking Methods

by Shao-Rong Wang^1,2,†, Tingting Xu^3,4,†, Kai Deng¹, Chi-Wai Wong⁵, Jinsong Liu⁴ and Wei-Shuo Fang^1,*

¹ State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 2A Nanwei Road, Beijing 100050, China

² Center for Drug Evaluation, China Food and Drug Administration, 1A Fuxing Road, Beijing 100038, China

³ School of Life Sciences, University of Science and Technology of China, Hefei 230026, China

⁴ State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China

⁵ NeuMed Pharmaceuticals Limited, Unit 509, 5/F BioTech Center I, No. 9 Science Park West Avenue, Shatin, Hong Kong, China

^† These authors contributed equally to this paper.

Molecules 2017, 22(5), 690; https://doi.org/10.3390/molecules22050690 - 26 Apr 2017

Cited by 7 | Viewed by 5843

Abstract

The pentacyclic triterpene oleanolic acid (OA, 1) with known farnesoid X receptor (FXR) modulatory activity was modified at its C-3 position to find new FXR-interacting agents. A diverse substitution library of OA derivatives was constructed in silico through a 2D fingerprint similarity [...] Read more.

The pentacyclic triterpene oleanolic acid (OA, 1) with known farnesoid X receptor (FXR) modulatory activity was modified at its C-3 position to find new FXR-interacting agents. A diverse substitution library of OA derivatives was constructed in silico through a 2D fingerprint similarity cluster strategy. With further docking analysis, four top-scored OA 3-O-ester derivatives were selected for synthesis. The bioassay results indicated that all four compounds 3 inhibited chenodeoxycholic acid (CDCA)-induced FXR transactivation in a concentration-dependent mode. Among them 3b and 3d are more active than the parent compound OA. A molecular simulation study was performed to attempt to explain the structure-activity relationship (SAR) and the antagonistic action. To the best of our knowledge, this is the first report on semi-synthetic pentacyclic triterpenoids with FXR-modulatory activities. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 1705 KiB

Open AccessArticle

The Effect of Deoxynivalenol on Selected Populations of Immunocompetent Cells in Porcine Blood—A Preliminary Study

by Michał Dąbrowski, Ewa Jakimiuk, Mirosław Baranowski, Magdalena Gajęcka, Łukasz Zielonka^* and Maciej Tadeusz Gajęcki

Department of Veterinary Prevention and Feed Hygiene, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland

Molecules 2017, 22(5), 691; https://doi.org/10.3390/molecules22050691 - 26 Apr 2017

Cited by 5 | Viewed by 4038

Abstract

Deoxynivalenol (DON) is one of the most prevalent mycotoxins in Europe. Pigs are an animal species that is most susceptible to this mycotoxin. Deoxynivalenol causes significant losses in pig production by lowering feed intake, decreasing daily weight gains, disrupting immune responses, and increasing [...] Read more.

Deoxynivalenol (DON) is one of the most prevalent mycotoxins in Europe. Pigs are an animal species that is most susceptible to this mycotoxin. Deoxynivalenol causes significant losses in pig production by lowering feed intake, decreasing daily weight gains, disrupting immune responses, and increasing susceptibility to diseases. The aim of this experiment was to determine the influence of feed contaminated with DON at concentrations insignificantly higher than recommended by the European Commission (900 µg/kg). The experimental feed contained 1008 μg DON/kg. The experiment was performed on eight weaners from the same litter. The animals were randomly divided into two groups: an experimental group (M, n = 4) fed contaminated feed and a control group (C, n = 4) administered feed free of mycotoxins. The experiment lasted for six weeks, and peripheral blood samples were collected from the animals for analyses of selected morphological parameters and changes in the percentages of CD4⁺8⁻, CD4⁻8⁺, and CD4⁺8⁺ lymphocytes and antigen-presenting cells (APC) with CD14⁺172⁺ (monocytes), CD172a^high4⁻14⁻ (conventional dendritic cells, cDC), and CD172a^dim4⁺14⁻ (plasmacytoid dendritic cells, pDC) phenotypes. The morphological parameters of porcine blood samples were determined by flow cytometry with non-fluorescent particle-size calibration standards, and no differences were observed between groups M and C. An immunophenotyping analysis of lymphocytes and dendritic cells (DC) revealed an increase in the percentage of CD4⁺8⁻, CD172a^high4⁻14⁻, and CD172a^dim4⁺14⁻ cells, and a decrease in the number of CD4⁻8⁺ cells in group M. The results of this experiment suggest that prolonged exposure to low doses of DON can change the proportions of immunocompetent cells (a shift towards humoral immunity), without affecting their overall counts. Full article

(This article belongs to the Section Natural Products Chemistry)

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19 pages, 3576 KiB

Open AccessArticle

Bioactive Components from Qingwen Baidu Decoction against LPS-Induced Acute Lung Injury in Rats

by Qi Zhang¹

, Hai-Min Lei¹

, Peng-Long Wang¹, Zhi-Qiang Ma¹, Yan Zhang², Jing-Jing Wu³, Jing Nie¹, Su-Juan Chen¹, Wen-Jie Han¹, Qing Wang¹, Dan-Yang Chen¹, Cheng-Ke Cai^1,* and Qiang Li^1,*

¹ School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China

² Fuzhou General Hospital of Chinese People ‘s Liberation Army, Fuzhou 350000, China

³ No. 476 Hospital of Chinese People ‘s Liberation Army, Fuzhou 350000, China

Molecules 2017, 22(5), 692; https://doi.org/10.3390/molecules22050692 - 26 Apr 2017

Cited by 18 | Viewed by 6512

Abstract

Qingwen Baidu Decoction (QBD) is an extraordinarily “cold” formula. It was traditionally used to cure epidemic hemorrhagic fever, intestinal typhoid fever, influenza, sepsis and so on. The purpose of this study was to discover relationships between the change of the constituents in different [...] Read more.

Qingwen Baidu Decoction (QBD) is an extraordinarily “cold” formula. It was traditionally used to cure epidemic hemorrhagic fever, intestinal typhoid fever, influenza, sepsis and so on. The purpose of this study was to discover relationships between the change of the constituents in different extracts of QBD and the pharmacological effect in a rat model of acute lung injury (ALI) induced by lipopolysaccharide (LPS). The study aimed to discover the changes in constituents of different QBD extracts and the pharmacological effects on acute lung injury (ALI) induced by LPS. The results demonstrated that high dose and middle dose of QBD had significantly potent anti-inflammatory effects and reduced pulmonary edema caused by ALI in rats (p < 0.05). To explore the underlying constituents of QBD, we assessed its influence of six different QBD extracts on ALI and analyzed the different constituents in the corresponding HPLC chromatograms by a Principal Component Analysis (PCA) method. The results showed that the pharmacological effect of QBD was related to the polarity of its extracts, and the medium polarity extracts E2 and E5 in particular displayed much better protective effects against ALI than other groups. Moreover, HPLC-DAD-ESI-MSⁿ and PCA analysis showed that verbascoside and angoroside C played a key role in reducing pulmonary edema. In addition, the current study revealed that ethyl gallate, pentagalloylglucose, galloyl paeoniflorin, mudanpioside C and harpagoside can treat ALI mainly by reducing the total cells and infiltration of activated polymorphonuclear leukocytes (PMNs). Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 1149 KiB

Open AccessArticle

Quantification of a Novel Photosensitizer of Chlorin e6-C15-Monomethyl Ester in Beagle Dog Plasma Using HPLC: Application to Pharmacokinetic Studies

by Xiuxiu Li^1,2, Jun Wen^1,2, Jingjing Jiang^1,2, Xin Zhao³, Tingting Zhou^1,2,* and Guorong Fan^1,2,4,5,*

¹ Shanghai Key Laboratory for Pharmaceutical Metabolite Research, School of Pharmacy, Second Military Medical University, Shanghai 200433, China

² Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, No. 325 Guohe Road, Shanghai 200433, China

³ Department of Pharmaceutical Analysis, School of Pharmacy, China Pharmaceutical University, No. 24 Tong Jia Xiang, Nanjing 210009, China

⁴ Department of Clinical Pharmacy, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, No. 100 Haining Road, Shanghai 200025, China

⁵ School of Medicine, Tongji University, No. 1239 Siping Road, Shanghai 200092, China

Molecules 2017, 22(5), 693; https://doi.org/10.3390/molecules22050693 - 26 Apr 2017

Cited by 4 | Viewed by 4802

Abstract

Chlorin e6-C15-monomethyl ester (CMME) is a novel photosensitizer, which is synthetized from the degradation products of silkworm excrement. Preclinical studies on the promising photosensitizer CMME are necessary to determine its therapeutic efficacy and druglikeness. A high-performance liquid chromatography with UV detection (HPLC–UV) method [...] Read more.

Chlorin e6-C15-monomethyl ester (CMME) is a novel photosensitizer, which is synthetized from the degradation products of silkworm excrement. Preclinical studies on the promising photosensitizer CMME are necessary to determine its therapeutic efficacy and druglikeness. A high-performance liquid chromatography with UV detection (HPLC–UV) method was established for the determination of CMME in beagle dog plasma. The sample preparation involved a protein-precipitation method with acetonitrile after the addition of tanshinone IIA as an internal standard (IS). CMME and the IS were separated on a Diamonsil C18 (2) column (100 mm × 4.6 mm, 5 μm) with a isocratic system of methanol–water containing 20 mM ammonium acetate with 0.3% glacial acetic acid (85:15, v/v). The flow rate was 1.0 mL/min with UV detection using a wavelength of 400 nm. The method was sensitive enough with a lower limit of quantitation (LLOQ) of 0.05 μg/mL and had a good linearity (r² > 0.999) over the linear range of 0.05–5.00 μg/mL. The intra-day and inter-day accuracies ranged from 98.5% to 102.8% and precisions (RSD) were within 6.8%. The validated method was successfully applied to the pharmacokinetic study of CMME after intravenous administration of single and multiple doses in beagle dogs. Full article

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10 pages, 1049 KiB

Open AccessArticle

Synthesis of Gibberellic Acid Derivatives and Their Effects on Plant Growth

by Hao Tian^1,2, Yiren Xu², Shaojin Liu¹, Dingsha Jin¹, Jianjun Zhang², Liusheng Duan¹ and Weiming Tan^1,*

¹ Engineering Research Centre of Plant Growth Regulators, Ministry of Education, College of Agronomy and Biotechnology, China Agricultural University, Beijing 100193, China

² Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China

Molecules 2017, 22(5), 694; https://doi.org/10.3390/molecules22050694 - 26 Apr 2017

Cited by 18 | Viewed by 11688

Abstract

A series of novel C-3-OH substituted gibberellin derivatives bearing an amide group were designed and synthesized from the natural product gibberellic acid (GA₃). Their activities on the plant growth regulation of rice and Arabidopsis were evaluated in vivo. Among these compounds, [...] Read more.

A series of novel C-3-OH substituted gibberellin derivatives bearing an amide group were designed and synthesized from the natural product gibberellic acid (GA₃). Their activities on the plant growth regulation of rice and Arabidopsis were evaluated in vivo. Among these compounds, 10d and 10f exhibited appreciable inhibitory activities on rice (48.6% at 100 μmol/L) and Arabidopsis (41.4% at 100 μmol/L), respectively. These results provide new insights into the design and synthesis of potential plant growth regulators. Full article

(This article belongs to the Section Organic Chemistry)

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12 pages, 1550 KiB

Open AccessArticle

Base-Promoted Synthesis of β-Substituted-Tryptophans via a Simple and Convenient Three-Component Condensation of Nickel(II) Glycinate

by Rui Zhou^1,2,†, Zhaoping Pan^1,3,†, Yuehua Zhang³, Fengbo Wu³, Qinglin Jiang^2,3,* and Li Guo^1,*

¹ West China School of Pharmacy, Sichuan University, Chengdu 610041, Sichuan, China

² Department of Medicinal Chemistry, School of Pharmacy, Chengdu Medical College, Chengdu 610500, Sichuan, China

³ Department of Pharmacy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China

^† These authors contributed equally.

Molecules 2017, 22(5), 695; https://doi.org/10.3390/molecules22050695 - 27 Apr 2017

Cited by 2 | Viewed by 4415

Abstract

A three-component reaction of nickel(II) glycinate was conducted for the convenient synthesis of β-substituted-tryptophans. The reaction worked smoothly under mild conditions and the procedure was simple and easy to handle. Full article

(This article belongs to the Section Organic Chemistry)

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7 pages, 781 KiB

Open AccessArticle

An Increased Understanding of Enolate Additions under Mechanochemical Conditions

by Heather Hopgood and James Mack^*

Department of Chemistry, University of Cincinnati, Cincinnati, OH 45221-0172, USA

Molecules 2017, 22(5), 696; https://doi.org/10.3390/molecules22050696 - 27 Apr 2017

Cited by 5 | Viewed by 6701

Abstract

Very little is known about enolate addition chemistry under solver-free mechanochemical conditions. In this report, we investigated the ability to selectively form products arising from the primary, secondary, and tertiary enolates under solvent-free conditions. Using potassium tert-butoxide as the base and primary, [...] Read more.

Very little is known about enolate addition chemistry under solver-free mechanochemical conditions. In this report, we investigated the ability to selectively form products arising from the primary, secondary, and tertiary enolates under solvent-free conditions. Using potassium tert-butoxide as the base and primary, secondary, and tertiary electrophiles, we were able to generate various enolate addition products including, 1,3,3,3-tetraphenyl-2,2-dimethyl-1-propanone; a molecule we did not observe under traditional solution-based conditions. Full article

(This article belongs to the Section Green Chemistry)

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11 pages, 2110 KiB

Open AccessArticle

Characterization of Compounds with Tumor–Cell Proliferation Inhibition Activity from Mushroom (Phellinus baumii) Mycelia Produced by Solid-State Fermentation

by Henan Zhang, Qian Shao, Wenhan Wang

, Jingsong Zhang, Zhong Zhang, Yanfang Liu and Yan Yang^*

Institute of Edible Fungi, Shanghai Academy of Agricultural Sciences, National Engineering Research Center of Edible Fungi, Key Laboratory of Edible Fungi Resources and Utilization (South), Ministry of Agriculture, Shanghai 201403, China

Molecules 2017, 22(5), 698; https://doi.org/10.3390/molecules22050698 - 27 Apr 2017

Cited by 23 | Viewed by 5457

Abstract

The inhibition of tumor-cell proliferationbyan organicsolvent extract from the solid-state fermentation of Phellinus baumii mycelia inoculated in rice medium was investigated in vitro. The active compounds inhibiting tumor-cell proliferation were characterized. Results revealed that all (petroleum ether, chloroform, ethyl acetate, and butanol) fractions [...] Read more.

The inhibition of tumor-cell proliferationbyan organicsolvent extract from the solid-state fermentation of Phellinus baumii mycelia inoculated in rice medium was investigated in vitro. The active compounds inhibiting tumor-cell proliferation were characterized. Results revealed that all (petroleum ether, chloroform, ethyl acetate, and butanol) fractions inhibited tumor-cell proliferation in a dose-dependent fashion. The ethyl acetate extract had the highest inhibitory effecton tumor-cell proliferation, and the butanol fraction had the lowest. Six compounds were isolated and purified from the ethyl acetate extract of P. baumii mycelia by the tandem application of silica-gel column chromatography (SGCC), high-speed countercurrent chromatography (HSCCC), and preparative HPLC. These compounds were identified by NMR and electrospray ionization-mass spectrometry (ESI-MS) spectroscopic methods as ergosterol (RF1), ergosta-7,22-dien-3β-yl pentadecanoate (RF3), 3,4-dihydroxy benzaldehyde(RF6), inoscavinA (RF7), baicalein(RF10), and 24-ethylcholesta-5,22-dien-3β-ol (RF13). To further clarify the activity of these compounds, the cell-proliferation-inhibition tests of these compounds on various tumor cells were carried out and evaluatedin vitro. Results suggested that compounds RF6, RF7, and RF10 had potent inhibition effects on the proliferation of a series of tumor cell lines, including K562, L1210, SW620, HepG2, LNCaP, and MCF-7cells. These findings indicated that P. baumii mycelia produced by solid-state fermentation in rice canbe used to obtain active compounds with the ability to inhibittumor-cell proliferation. Full article

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13 pages, 2527 KiB

Open AccessArticle

Pectic Bee Pollen Polysaccharide from Rosa rugosa Alleviates Diet-Induced Hepatic Steatosis and Insulin Resistance via Induction of AMPK/mTOR-Mediated Autophagy

by Xinzhi Li^†, Haiquan Gong^†, Siwen Yang, Lulu Yang, Yuying Fan^*

and Yifa Zhou^*

¹ School of Life Sciences, Northeast Normal University, Changchun 130024, China

^† These authors contributed equally to the paper.

Molecules 2017, 22(5), 699; https://doi.org/10.3390/molecules22050699 - 28 Apr 2017

Cited by 81 | Viewed by 8689

Abstract

Despite it is used as a nutraceutical against diabetes and obesity, the mechanism of action of bee pollen is still unclear. Pectic bee pollen polysaccharide (RBPP-P) was isolated from Rosa rugosa, and its structure was characterized by ¹³C-NMR and Fourier transform-infrared [...] Read more.

Despite it is used as a nutraceutical against diabetes and obesity, the mechanism of action of bee pollen is still unclear. Pectic bee pollen polysaccharide (RBPP-P) was isolated from Rosa rugosa, and its structure was characterized by ¹³C-NMR and Fourier transform-infrared spectroscopy (FT-IR). Using high glucose and fatty acids-treated HepG2 cells and high fat diet (HFD)-induced obesity mice, we detected its effect on insulin function and lipid metabolism based on autophagy. RBPP-P contained arabinogalactan, rhamnogalacturonan I, and homogalacturonan domains. In vivo studies demonstrated that RBPP-P markedly ameliorated insulin resistance, glucose intolerance, and liver steatosis in obese mice. The suppressive effects of RBPP-P on liver steatosis and triglyceride content were mediated by increased autophagy and lipase expression in liver. In AMPK knockdown cells (prkaa 1/2^−/− MEF) and HFD-fed mice tissues (liver, gonadal white adipose, and inguinal white adipose), RBPP-P enhanced autophagy in AMPK/mTOR-dependent way in liver, but not in adipose tissue. These findings demonstrated that bee pollen polysaccharide alleviated liver steatosis and insulin resistance by promoting autophagy via an AMPK/mTOR-mediated signaling pathway, suggesting that RBPP-P could be a novel therapeutic agent used for the treatment of obesity and diabetes. Full article

(This article belongs to the Collection Bioactive Compounds)

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13 pages, 1109 KiB

Open AccessArticle

Formulation, Characterization and Properties of Hemp Seed Oil and Its Emulsions

by Veronika Mikulcová¹, Věra Kašpárková^1,2,*, Petr Humpolíček^2,3

and Leona Buňková⁴

¹ Department of Fat, Surfactant and Cosmetics Technology, Faculty of Technology, Tomas Bata University in Zlin, nam. T. G. Masaryka 5555, 760 01 Zlin, Czech Republic

² Centre of Polymer Systems, Tomas Bata University in Zlin, nam. T. G. Masaryka 5555, 760 01 Zlin, Czech Republic

³ Polymer Centre, Faculty of Technology, Tomas Bata University in Zlin, 760 01 Zlin, Czech Republic

⁴ Department of Environmental Protection and Engineering, Faculty of Technology, Tomas Bata University in Zlin, nam. T. G. Masaryka 5555, 760 01 Zlin, Czech Republic

Molecules 2017, 22(5), 700; https://doi.org/10.3390/molecules22050700 - 27 Apr 2017

Cited by 103 | Viewed by 18553

Abstract

The formulation, characterization, and anticipated antibacterial properties of hemp seed oil and its emulsions were investigated. The oil obtained from the seeds of Cannabis sativa L. in refined and unrefined form was characterized using iodine, saponification, acid values, and gas chromatography, and was [...] Read more.

The formulation, characterization, and anticipated antibacterial properties of hemp seed oil and its emulsions were investigated. The oil obtained from the seeds of Cannabis sativa L. in refined and unrefined form was characterized using iodine, saponification, acid values, and gas chromatography, and was employed for the preparation of stable oil-in-water emulsions. The emulsions were prepared using pairs of non-ionic surfactants (Tween, Span). The effects of the emulsification method (spontaneous emulsification vs. high-intensity stirring), hydrophilic lipophilic balance (HLB), type and concentration of surfactant, and oil type on the size and distribution of the emulsion particles were investigated. It was found that the ability to form stable emulsions with small, initial particle sizes is primarily dependent on the given method of preparation and the HLB value. The most efficient method of emulsification that afforded the best emulsions with the smallest particles (151 ± 1 nm) comprised the high-energy method, and emulsions stable over the long-term were observed at HBL 9 with 10 wt % concentration of surfactants. Under high-intensity emulsification, refined and unrefined oils performed similarly. The oils as well as their emulsions were tested against the growth of selected bacteria using the disk diffusion and broth microdilution methods. The antibacterial effect of hemp seed oil was documented against Micrococcus luteus and Staphylococcus aureus subsp. aureus. The formulated emulsions did not exhibit the antibacterial activity that had been anticipated. Full article

(This article belongs to the Special Issue Antibacterial Materials and Coatings)

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20 pages, 3321 KiB

Open AccessArticle

Silver Nanoparticles Mediated by Costus afer Leaf Extract: Synthesis, Antibacterial, Antioxidant and Electrochemical Properties

by Elias E. Elemike^1,2,3, Omolola E. Fayemi^1,2, Anthony C. Ekennia⁴, Damian C. Onwudiwe^1,2,* and Eno E. Ebenso^1,2

¹ Material Science Innovation and Modelling (MaSIM) Research Focus Area, Faculty of Agriculture, Science and Technology, North-West University, Mafikeng Campus, Private Bag X2046, Mmabatho 2735, South Africa

² Department of Chemistry, School of Mathematics and Physical Sciences, Faculty of Agriculture, Science and Technology, North-West University, Mafikeng Campus, Private Bag X2046, Mmabatho 2735, South Africa

³ Department of Chemistry, College of Science, Federal University of Petroleum Resources, P.M.B 1221 Effurun, Delta State, Nigeria

⁴ Department of Chemistry, Federal University Ndufu-Alike Ikwo (FUNAI), P.M.B 1010 Abakiliki, Ebonyi State, Nigeria

Molecules 2017, 22(5), 701; https://doi.org/10.3390/molecules22050701 - 29 Apr 2017

Cited by 86 | Viewed by 10229

Abstract

Synthesis of metallic and semiconductor nanoparticles through physical and chemical routes has been extensively reported. However, green synthesized metal nanoparticles are currently in the limelight due to the simplicity, cost-effectiveness and eco-friendliness of their synthesis. This study explored the use of aqueous leaf [...] Read more.

Synthesis of metallic and semiconductor nanoparticles through physical and chemical routes has been extensively reported. However, green synthesized metal nanoparticles are currently in the limelight due to the simplicity, cost-effectiveness and eco-friendliness of their synthesis. This study explored the use of aqueous leaf extract of Costus afer in the synthesis of silver nanoparticles (CA-AgNPs). The optical and structural properties of the resulting silver nanoparticles were studied using UV-visible spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Fourier transform infra–red spectrophotometer (FTIR). TEM images of the silver nanoparticles confirmed the existence of monodispersed spherical nanoparticles with a mean size of 20 nm. The FTIR spectra affirmed the presence of phytochemicals from the Costus afer leaf extract on the surface of the silver nanoparticles. The electrochemical characterization of a CA-AgNPs/multiwalled carbon nanotubes (MWCNT)-modified electrode was carried out to confirm the charge transfer properties of the nanocomposites. The comparative study showed that the CA-AgNPs/MWCNT-modified electrode demonstrated faster charge transport behaviour. The anodic current density of the electrodes in Fe(CN)₆]⁴⁻/[Fe(CN)₆]³⁻ redox probe follows the order: GCE/CA-Ag/MWCNT (550 mA/cm²) > GCE/MWCNT (270 mA/cm²) > GCE (80 mA/cm²) > GCE/CA-Ag (7.93 mA/cm²). The silver nanoparticles were evaluated for their antibacterial properties against Gram negative (Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa) and Gram positive (Bacillus subtilis and Staphylococcus aureus) pathogens. The nanoparticles exhibited better inhibition of the bacterial strains compared to the precursors (leaf extract of Costus afer and silver nitrate). Furthermore, the ability of the nanoparticles to scavenge DPPH radicals at different concentrations was studied using the DPPH radical scavenging assay and compared to that of the leaf extract and ascorbic acid. The nanoparticles were better DPPH scavengers compared to the leaf extract and their antioxidant properties compared favorably the antioxidant results of ascorbic acid. The green approach to nanoparticles synthesis carried out in this research work is simple, non-polluting, inexpensive and non-hazardous. Full article

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

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16 pages, 2438 KiB

Open AccessArticle

Protective Effect of Caffeic Acid Derivatives on tert-Butyl Hydroperoxide-Induced Oxidative Hepato-Toxicity and Mitochondrial Dysfunction in HepG2 Cells

by Tzung-Hsun Tsai^1,†, Chun-Hsien Yu^2,3,†

, Yu-Ping Chang⁴, Yu-Ting Lin⁴, Ching-Jang Huang⁵, Yueh-Hsiung Kuo^6,7,*

and Po-Jung Tsai^4,*

¹ Department of Dentistry, Keelung Chang-Gung Memorial Hospital, Keelung 204, Taiwan

² Department of Pediatrics, Taipei Tzu-Chi Hospital, Buddhist Tzu-Chi Medical Foundation, New Taipei City 231, Taiwan

³ Department of Pediatrics, College of Medicine, Buddhist Tzu-Chi University, Hualien 970, Taiwan

⁴ Department of Human Development and Family Studies, National Taiwan Normal University, Taipei 106, Taiwan

⁵ Institute of Microbiology and Biochemistry, and Department of Biochemical Science and Technology, National Taiwan University, Taipei 106, Taiwan

⁶ Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan

⁷ Department of Biotechnology, Asia University, Taichung 413, Taiwan

^† These authors contributed equally to this work.

Molecules 2017, 22(5), 702; https://doi.org/10.3390/molecules22050702 - 28 Apr 2017

Cited by 29 | Viewed by 6181

Abstract

Oxidative stress results in structural and functional abnormalities in the liver and is thought to be a crucial factor in liver diseases. The aim of this study was to investigate the cytoprotective and antioxidant effects of caffeic acid (CA) derivatives on tert-butyl [...] Read more.

Oxidative stress results in structural and functional abnormalities in the liver and is thought to be a crucial factor in liver diseases. The aim of this study was to investigate the cytoprotective and antioxidant effects of caffeic acid (CA) derivatives on tert-butyl hydroperoxide (t-BHP)-induced oxidative stress in HepG2 cells. Nine CA derivatives were synthesized, including N-phenylethyl caffeamide (PECA), N-(3-florophen)methyl caffeamide (FMCA), N-(4-methoxy-phen)methyl caffeamide (MPMCA), N-heptyl caffeamide (HCA), N-octyl caffeamide (OCA), octyl caffeate (CAOE), phenpropyl caffeate (CAPPE), phenethyl caffeate (CAPE), and phenmethyl caffeate (CAPME). The results showed that CA and its derivatives significantly inhibited t-BHP-induced cell death of HepG2 cells. The rank order of potency of the CA derivatives for cytoprotection was CAOE > HCA > OCA > FMCA > CAPPE > CAPME > CAPE > PECA > MPMCA > CA. Their cytoprotective activity was associated with lipophilicity. The antioxidant effect of these compounds was supported by the reduction in the levels of thiobarbituric acid reactive substrates, a biomarker of lipid peroxidation, in HepG2 cells. Pre-treatment of CA derivatives significantly prevented the depletion of glutathione, the most important water-soluble antioxidant in hepatocytes. Pre-treatment of CA derivatives before t-BHP exposure maintained mitochondrial oxygen consumption rate and ATP content in the injured HepG2 cells. CA derivatives except OCA and HCA significantly suppressed t-BHP-induced hypoxia-inducible factor-1α (HIF-1α) protein level. In addition, all of these CA derivatives markedly increased the nuclear factor erythroid 2-related factor 2 (Nrf2) accumulation in the nucleus, indicating that their cytoprotection may be mediated by the activation of Nrf2. Our results suggest that CA derivatives might be a hepatoprotective agent against oxidative stress. Full article

(This article belongs to the Section Medicinal Chemistry)

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14 pages, 1419 KiB

Open AccessArticle

Chemical Composition, Antioxidant and α-Glucosidase-Inhibiting Activities of the Aqueous and Hydroethanolic Extracts of Vaccinium myrtillus Leaves

by Kristina Bljajić¹, Roberta Petlevski¹, Lovorka Vujić¹

, Ana Čačić^1,2, Nina Šoštarić¹

, Jasna Jablan¹

, Isabel Saraiva de Carvalho²

and Marijana Zovko Končić^1,*

¹ Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, 10000 Zagreb, Croatia

² Faculty of Sciences and Technology, University of Algarve, Campus de Gambelas, Bd. 8, 8005-139 Faro, Portugal

Molecules 2017, 22(5), 703; https://doi.org/10.3390/molecules22050703 - 28 Apr 2017

Cited by 53 | Viewed by 6821

Abstract

Vaccinium myrtillus (bilberry) leaf is traditionally used in southeastern Europe for the treatment of diabetes. In the present study, the ability of bilberry leaf extracts to inhibit carbohydrate-hydrolyzing enzymes and restore glutathione concentration in Hep G2 cells subjected to glucose-induced oxidative stress was [...] Read more.

Vaccinium myrtillus (bilberry) leaf is traditionally used in southeastern Europe for the treatment of diabetes. In the present study, the ability of bilberry leaf extracts to inhibit carbohydrate-hydrolyzing enzymes and restore glutathione concentration in Hep G2 cells subjected to glucose-induced oxidative stress was investigated. A comprehensive analysis of the antioxidant activity of two bilberry leaf extracts was performed. The aqueous extract showed excellent total antioxidant and chelating activity. Its antioxidant activity in the β-carotene-linoleic acid assay was very good, reaching the activity of the antioxidant standard BHA (93.4 ± 2.3% vs. 95.1 ± 2.4%, respectively). The hydroethanolic extract (ethanol/H₂O, 8:2, v/v), on the other hand, was a better radical scavenger and Fe²⁺ reducing agent. Furthermore, the aqueous extract was able to efficiently increase glutathione concentration in Hep G2 cells subjected to glucose-induced oxidative stress and restore it to the levels observed in non-hyperglycaemic cells. The hydroethanolic extract strongly inhibited α-glucosidase, with the IC₅₀ statistically equal to the antidiabetic drug acarbose (0.29 ± 0.02 mg/mL vs. 0.50 ± 0.01 mg/mL, respectively). Phytochemical analysis revealed the presence of quercetin and kaemferol derivatives, as well as chlorogenic and p-coumaric acid. The study results indicate that V. myrtillus leaf may have promising properties as a supporting therapy for diabetes. Full article

(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)

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15 pages, 1841 KiB

Open AccessArticle

Electrochemical Enhancement of Photocatalytic Disinfection on Aligned TiO₂ and Nitrogen Doped TiO₂ Nanotubes

by Cristina Pablos^1,*, Javier Marugán¹

, Rafael Van Grieken¹, Patrick Stuart Morris Dunlop², Jeremy William John Hamilton², Dionysios D. Dionysiou³ and John Anthony Byrne²

¹ Department of Chemical and Environmental Technology, ESCET, Universidad Rey Juan Carlos, c/Tulipán s/n, 28933 Móstoles, Madrid, Spain

² Nanotechnology and Integrated BioEngineering Centre (NIBEC), Ulster University, Newtownabbey BT37 0QB, Northern Ireland, UK

³ Environmental Engineering and Science program, University of Cincinnati, 705 Engineering Research Center, Cincinnati, OH 45221, USA

Molecules 2017, 22(5), 704; https://doi.org/10.3390/molecules22050704 - 28 Apr 2017

Cited by 39 | Viewed by 8339

Abstract

TiO₂ photocatalysis is considered as an alternative to conventional disinfection processes for the inactivation of waterborne microorganisms. The efficiency of photocatalysis is limited by charge carrier recombination rates. When the photocatalyst is immobilized on an electrically conducting support, one may assist charge [...] Read more.

TiO₂ photocatalysis is considered as an alternative to conventional disinfection processes for the inactivation of waterborne microorganisms. The efficiency of photocatalysis is limited by charge carrier recombination rates. When the photocatalyst is immobilized on an electrically conducting support, one may assist charge separation by the application of an external electrical bias. The aim of this work was to study electrochemically assisted photocatalysis with nitrogen doped titania photoanodes under visible and UV-visible irradiation for the inactivation of Escherichia coli. Aligned TiO₂ nanotubes were synthesized (TiO₂-NT) by anodizing Ti foil. Nanoparticulate titania films were made on Ti foil by electrophoretic coating (P25 TiO₂). N-doped titania nanotubes and N,F co-doped titania films were also prepared with the aim of extending the active spectrum into the visible. Electrochemically assisted photocatalysis gave higher disinfection efficiency in comparison to photocatalysis (electrode at open circuit) for all materials tested. It is proposed that electrostatic attraction of negatively charged bacteria to the positively biased photoanodes leads to the enhancement observed. The N-doped TiO₂ nanotube electrode gave the most efficient electrochemically assisted photocatalytic inactivation of bacteria under UV-Vis irradiation but no inactivation of bacteria was observed under visible only irradiation. The visible light photocurrent was only a fraction (2%) of the UV response. Full article

(This article belongs to the Special Issue Photon-involving Purification of Water and Air)

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9 pages, 2444 KiB

Open AccessArticle

Generation and Applications of a DNA Aptamer against Gremlin-1

by Qian Li^1,†, Yongwei Huo^2,†, Yonghong Guo³, Xiaoyan Zheng¹, Wengang Sun¹ and Zhiming Hao^1,*

¹ Department of Rheumatology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China

² Research Center of Reproductive Medicine, Medical School of Xi’an Jiaotong University, Xi’an 710061, China

³ Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China

^† These authors contributed equally to this work.

Molecules 2017, 22(5), 706; https://doi.org/10.3390/molecules22050706 - 28 Apr 2017

Cited by 11 | Viewed by 7273

Abstract

Gremlin-1, a highly conserved glycosylated and phosphorylated secretory protein, plays important roles in diverse biological processes including early embryonic development, fibrosis, tumorigenesis, and renal pathophysiology. Aptamers, which are RNA or DNA single-stranded oligonucleotides capable of binding specifically to different targets ranging from small [...] Read more.

Gremlin-1, a highly conserved glycosylated and phosphorylated secretory protein, plays important roles in diverse biological processes including early embryonic development, fibrosis, tumorigenesis, and renal pathophysiology. Aptamers, which are RNA or DNA single-stranded oligonucleotides capable of binding specifically to different targets ranging from small organics to whole cells, have potential applications in targeted imaging, diagnosis and therapy. In this study, we obtained a DNA aptamer against Gremlin-1 (G-ap49) using in vitro Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Binding assay and dot-blot showed that G-ap49 had high affinity for Gremlin-1. Further experiments indicated that G-ap49 was quite stable in a cell culture system and could be used in South-Western blot analysis, enzyme-linked aptamer sorbent assay (ELASA), and aptamer-based cytochemistry and histochemistry staining to detect Gremlin-1. Moreover, our study demonstrated that G-ap49 is capable of revealing the subcellular localization of Gremlin-1. These data indicate that G-ap49 can be used as an alternative to antibodies in detecting Gremlin-1. Full article

(This article belongs to the Special Issue Synthesis and Applications of Oligonucleotide Conjugates)

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16 pages, 2196 KiB

Open AccessFeature PaperArticle

Selenium Speciation in the Fountain Creek Watershed (Colorado, USA) Correlates with Water Hardness, Ca and Mg Levels

by James S. Carsella^1,2, Irma Sánchez-Lombardo^3,4, Sandra J. Bonetti¹ and Debbie C. Crans^2,3,*

¹ Department of Chemistry, Colorado State University–Pueblo, 2200 Bonforte Blvd, Pueblo, CO 81001, USA

² Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO 80523, USA

³ Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA

⁴ División de Ciencias Básicas, Universidad Juárez Autónoma de Tabasco, Cunduacán, Tabasco 86690, Mexico

Molecules 2017, 22(5), 708; https://doi.org/10.3390/molecules22050708 - 30 Apr 2017

Cited by 10 | Viewed by 6040

Abstract

The environmental levels of selenium (Se) are regulated and strictly enforced by the Environmental Protection Agency (EPA) because of the toxicity that Se can exert at high levels. However, speciation plays an important role in the overall toxicity of Se, and only when [...] Read more.

The environmental levels of selenium (Se) are regulated and strictly enforced by the Environmental Protection Agency (EPA) because of the toxicity that Se can exert at high levels. However, speciation plays an important role in the overall toxicity of Se, and only when speciation analysis has been conducted will a detailed understanding of the system be possible. In the following, we carried out the speciation analysis of the creek waters in three of the main tributaries—Upper Fountain Creek, Monument Creek and Lower Fountain Creek—located in the Fountain Creek Watershed (Colorado, USA). There are statistically significant differences between the Se, Ca and Mg, levels in each of the tributaries and seasonal swings in Se, Ca and Mg levels have been observed. There are also statistically significant differences between the Se levels when grouped by Pierre Shale type. These factors are considered when determining the forms of Se present and analyzing their chemistry using the reported thermodynamic relationships considering Ca²⁺, Mg²⁺, SeO₄²⁻, SeO₃²⁻ and carbonates. This analysis demonstrated that the correlation between Se and water hardness can be explained in terms of formation of soluble CaSeO₄. The speciation analysis demonstrated that for the Fountain Creek waters, the Ca²⁺ ion may be mainly responsible for the observed correlation with the Se level. Considering that the Mg²⁺ level is also correlating linearly with the Se levels it is important to recognize that without Mg²⁺ the Ca²⁺ would be significantly reduced. The major role of Mg²⁺ is thus to raise the Ca²⁺ levels despite the equilibria with carbonate and other anions that would otherwise decrease Ca²⁺ levels. Full article

(This article belongs to the Special Issue Celebrating Two Centuries of Research in Selenium Chemistry: State of the Art and New Prospectives)

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26 pages, 11158 KiB

Open AccessArticle

Multi-Anti-Parasitic Activity of Arylidene Ketones and Thiazolidene Hydrazines against Trypanosoma cruzi and Leishmania spp.

by Guzmán Álvarez^1,*

, Cintya Perdomo¹, Cathia Coronel², Elena Aguilera³

, Javier Varela³, Gonzalo Aparicio^4,5

, Flavio R. Zolessi^4,5

, Nallely Cabrera⁶, Celeste Vega², Miriam Rolón², Antonieta Rojas de Arias², Ruy Pérez-Montfort⁶, Hugo Cerecetto³ and Mercedes González³

¹ Laboratorio de Moléculas Bioactivas, CENUR Litoral Norte, Universidad de la República, Ruta 3 (km 363), Paysandú, C.P. 60000, Uruguay

² Centro Para el Desarrollo de la Investigación Científica (CEDIC/FMB/Diaz Gill Medicina Laboratorial), Asunción, C.P. 1255, Paraguay

³ Grupo de Química Medicinal-Laboratorio de Química Orgánica, Facultad de Ciencias, Universidad de la República, Montevideo, C.P. 11400, Uruguay

⁴ Sección Biología Celular, Facultad de Ciencias, Universidad de la República, Montevideo, C.P. 11400, Uruguay

⁵ Cell Biology of Neural Development Laboratory, Institut Pasteur de Montevideo, Montevideo, C.P. 11400, Uruguay

⁶ Departamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de México, C.P. 04510, Mexico

Molecules 2017, 22(5), 709; https://doi.org/10.3390/molecules22050709 - 7 May 2017

Cited by 26 | Viewed by 6235

Abstract

A series of fifty arylideneketones and thiazolidenehydrazines was evaluated against Leishmania infantum and Leishmania braziliensis. Furthermore, new simplified thiazolidenehydrazine derivatives were evaluated against Trypanosoma cruzi. The cytotoxicity of the active compounds on non-infected fibroblasts or macrophages was established in vitro to [...] Read more.

A series of fifty arylideneketones and thiazolidenehydrazines was evaluated against Leishmania infantum and Leishmania braziliensis. Furthermore, new simplified thiazolidenehydrazine derivatives were evaluated against Trypanosoma cruzi. The cytotoxicity of the active compounds on non-infected fibroblasts or macrophages was established in vitro to evaluate the selectivity of their anti-parasitic effects. Seven thiazolidenehydrazine derivatives and ten arylideneketones had good activity against the three parasites. The IC₅₀ values for T. cruzi and Leishmania spp. ranged from 90 nM–25 µM. Eight compounds had multi-trypanocidal activity against T. cruzi and Leishmania spp. (the etiological agents of cutaneous and visceral forms). The selectivity of these active compounds was better than the three reference drugs: benznidazole, glucantime and miltefosine. They also had low toxicity when tested in vivo on zebrafish. Trying to understand the mechanism of action of these compounds, two possible molecular targets were investigated: triosephosphate isomerase and cruzipain. We also used a molecular stripping approach to elucidate the minimal structural requirements for their anti-T. cruzi activity. Full article

(This article belongs to the Special Issue Polypharmacology and Multitarget Drug Discovery)

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12 pages, 837 KiB

Open AccessArticle

Adamantane-Isothiourea Hybrid Derivatives: Synthesis, Characterization, In Vitro Antimicrobial, and In Vivo Hypoglycemic Activities

by Lamya H. Al-Wahaibi¹, Hanan M. Hassan², Amal M. Abo-Kamar^2,3, Hazem A. Ghabbour⁴

and Ali A. El-Emam^4,*

¹ Department of Chemistry, College of Sciences, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia

² Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia

³ Department of Microbiology, Faculty of Pharmacy, Tanta University, Tanta, Egypt

⁴ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11671, Saudi Arabia

Molecules 2017, 22(5), 710; https://doi.org/10.3390/molecules22050710 - 29 Apr 2017

Cited by 39 | Viewed by 5958

Abstract

A new series of adamantane-isothiourea hybrid derivatives, namely 4-arylmethyl (Z)-N′-(adamantan-1-yl)-morpholine-4-carbothioimidates 7a–e and 4-arylmethyl (Z)-N′-(adamantan-1-yl)-4-phenylpiperazine-1-carbothioimidates 8a–e were prepared via the reaction of N-(adamantan-1-yl)morpholine-4-carbothioamide 5 and N-(adamantan-1-yl)-4-phenylpiperazine-1-carbothioamide 6 with benzyl or [...] Read more.

A new series of adamantane-isothiourea hybrid derivatives, namely 4-arylmethyl (Z)-N′-(adamantan-1-yl)-morpholine-4-carbothioimidates 7a–e and 4-arylmethyl (Z)-N′-(adamantan-1-yl)-4-phenylpiperazine-1-carbothioimidates 8a–e were prepared via the reaction of N-(adamantan-1-yl)morpholine-4-carbothioamide 5 and N-(adamantan-1-yl)-4-phenylpiperazine-1-carbothioamide 6 with benzyl or substituted benzyl bromides, in acetone, in the presence of anhydrous potassium carbonate. The structures of the synthesized compounds were confirmed by ¹H-NMR, ¹³C-NMR, electrospray ionization mass spectral (ESI-MS) data, and X-ray crystallographic data. The in vitro antimicrobial activity of the new compounds was determined against certain standard strains of pathogenic bacteria and the yeast-like pathogenic fungus Candida albicans. Compounds 7b, 7d and 7e displayed potent broad-spectrum antibacterial activity, while compounds 7a, 7c, 8b, 8d and 8e were active against the tested Gram-positive bacteria. The in vivo oral hypoglycemic activity of the new compounds was carried on streptozotocin (STZ)-induced diabetic rats. Compounds 7a, 8ab, and 8b produced potent dose-independent reduction of serum glucose levels, compared to the potent hypoglycemic drug gliclazide. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 6757 KiB

Open AccessArticle

MALDI-MS Imaging of Urushiols in Poison Ivy Stem

by Mina Aziz¹, Drew Sturtevant¹, Jordan Winston², Eva Collakova², John G. Jelesko^2,*

and Kent D. Chapman^1,*

¹ Department of Biological Sciences, BioDiscovery Institute, University of North Texas, Denton, TX 76203, USA

² Department of Plant Pathology, Physiology, and Weed Science, Virginia Tech University, Blacksburg, VA 24061, USA

Molecules 2017, 22(5), 711; https://doi.org/10.3390/molecules22050711 - 29 Apr 2017

Cited by 23 | Viewed by 7930

Abstract

Urushiols are the allergenic components of Toxicodendron radicans (poison ivy) as well as other Toxicodendron species. They are alk-(en)-yl catechol derivatives with a 15- or 17-carbon side chain having different degrees of unsaturation. Although several methods have been developed for analysis of urushiols [...] Read more.

Urushiols are the allergenic components of Toxicodendron radicans (poison ivy) as well as other Toxicodendron species. They are alk-(en)-yl catechol derivatives with a 15- or 17-carbon side chain having different degrees of unsaturation. Although several methods have been developed for analysis of urushiols in plant tissues, the in situ localization of the different urushiol congeners has not been reported. Here, we report on the first analysis of urushiols in poison ivy stems by matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI). Our results show that the urushiol congeners with 15-carbon side chains are mainly localized to the resin ducts, while those with 17-carbon side chains are widely distributed in cortex and vascular tissues. The presence of these urushiols in stem extracts of poison ivy seedlings was confirmed by GC-MS. These novel findings provide new insights into the spatial tissue distribution of urushiols that might be biosynthetically or functionally relevant. Full article

(This article belongs to the Special Issue Expanding the Potential of Metabolomics for Under Investigated Organisms and in Drug Discovery)

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9 pages, 869 KiB

Open AccessArticle

4-Hydroxy-7-methyl-3-phenylcoumarin Suppresses Aflatoxin Biosynthesis via Downregulation of aflK Expressing Versicolorin B Synthase in Aspergillus flavus

by Young-Sun Moon^1,†

, Leesun Kim^1,†, Hyang Sook Chun^2,‡ and Sung-Eun Lee^1,*,‡

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

² Advanced Food Safety Research Group, BK21 Plus, School of Food Science and Technology, Chung-Ang University, Anseong 17546, Korea

^† Authors equally contributed to this paper as first authors.

^‡ Authors equally contributed to this paper as corresponding authors.

Molecules 2017, 22(5), 712; https://doi.org/10.3390/molecules22050712 - 29 Apr 2017

Cited by 15 | Viewed by 5869

Abstract

Naturally occurring coumarins possess antibacterial and antifungal properties. In this study, these natural and synthetic coumarins were used to evaluate their antifungal activities against Aspergillus flavus, which produces aflatoxins. In addition to control antifungal activities, antiaflatoxigenic properties were also determined using a [...] Read more.

Naturally occurring coumarins possess antibacterial and antifungal properties. In this study, these natural and synthetic coumarins were used to evaluate their antifungal activities against Aspergillus flavus, which produces aflatoxins. In addition to control antifungal activities, antiaflatoxigenic properties were also determined using a high-performance liquid chromatography in conjunction with fluorescence detection. In this study, 38 compounds tested and 4-hydroxy-7-methyl-3-phenyl coumarin showed potent antifungal and antiaflatoxigenic activities against A. flavus. Inhibitory mode of antiaflatoxigenic action by 4-hydroxy-7-methyl-3-phenyl coumarin was based on the downregulation of aflD, aflK, aflQ, and aflR in aflatoxin biosynthesis. In the cases of coumarins, antifungal and aflatoxigenic activities are highly related to the lack of diene moieties in the structures. In structurally related compounds, 2,3-dihydrobenzofuran exhibited antifungal and antiaflatoxigenic activities against A. flavus. The inhibitory mode of antiaflatoxigenic action by 2,3-dihydrobenzofuran was based on the inhibition of the transcription factor (aflS) in the aflatoxin biosynthesis pathway. These potent inhibitions of 2,3-dihydrobenzofuran and 4-hydroxy-7-methyl-3-phenyl coumarin on the Aspergillus growth and production of aflatoxins contribute to the development of new controlling agents to mitigate aflatoxin contamination. Full article

(This article belongs to the Special Issue Structure, Chemical Analysis, Biosynthesis, Metabolism, Molecular Engineering and Biological Functions of Phytoalexins)

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14 pages, 946 KiB

Open AccessArticle

Markers of Oxidative Stress and Antioxidant Defense in Romanian Patients with Type 2 Diabetes Mellitus and Obesity

by Ariana Picu^1,2, Laura Petcu^1,2,*, Simona Ştefan¹, Manuela Mitu¹, Daniela Lixandru³, Constantin Ionescu-Tîrgovişte^1,3, Grațiela Grădișteanu Pîrcălăbioru^2,4

, Felicia Ciulu-Costinescu⁴, Maria-Viorica Bubulica⁵ and Mariana Carmen Chifiriuc^2,4

¹ NIDNMD “Prof. N.C. Paulescu”, 2th district, Bucharest 020042, Romania

² Faculty of Biology, University of Bucharest, 5th district, Bucharest 050095, Romania

³ Department of Biochemstry, University of Medicine and Pharmacy “Carol Davila”, 5th district, Bucharest 050474, Romania

⁴ Research Institute of the University of Bucharest, ICUB, 5th district, Bucharest 050107, Romania

⁵ Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, Petru Rareș Str., Craiova 200638, Romania

Molecules 2017, 22(5), 714; https://doi.org/10.3390/molecules22050714 - 1 May 2017

Cited by 48 | Viewed by 6826

Abstract

Type 2 diabetes mellitus (T2DM) is strongly associated with obesity. The adipose tissue secretes bioactive adipokines leading to low grade inflammation, amplified by oxidative stress, which promotes the formation of advanced glycation end products and eventually leads to dyslipidemia and vascular complications. The [...] Read more.

Type 2 diabetes mellitus (T2DM) is strongly associated with obesity. The adipose tissue secretes bioactive adipokines leading to low grade inflammation, amplified by oxidative stress, which promotes the formation of advanced glycation end products and eventually leads to dyslipidemia and vascular complications. The aim of this study was to correlate anthropometric, biochemical and oxidative stress parameters in newly diagnosed (ND) T2DM patients and to investigate the role of oxidative stress in T2DM associated with obesity. A group of 115 ND- T2DM patients was compared to a group of 32 healthy subjects in terms of clinical, anthropometric, biochemical and oxidative stress parameters. ND-T2DM patients had significantly lower adiponectin, glutathione (GSH) and gluthatione peroxidase (GPx) and elevated insulin, proinsulin, HOMA-IR index, proinsulin/insulin (P/I) and proinsulin/adiponectin (P/A) ratio, fructosamine, and total oxidant status (TOS). The total body fat mass was positively correlated with total oxidant status (TOS). Positive correlations were found between TOS and glycated hemoglobin (HbA1c), and between TOS and glycaemia. Negative correlations were identified between: GPx and glycaemia, GPx and HbA1c, and also between GSH and fructosamine. The total antioxidant status was negatively correlated with the respiratory burst. The identified correlations suggest the existence of a complex interplay between diabetes, obesity and oxidative stress. Full article

(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)

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9 pages, 4166 KiB

Open AccessArticle

Anti-Inflammatory Effects, SAR, and Action Mechanism of Monoterpenoids from Radix Paeoniae Alba on LPS-Stimulated RAW 264.7 Cells

by Xiaoxu Bi¹, Li Han^1,*, Tiange Qu², Yu Mu¹, Peipei Guan¹, Xiaodan Qu¹, Zhanyou Wang¹ and Xueshi Huang^1,*

¹ College of Life and Health Sciences, Northeastern University, Shenyang 110819, China

² Dongzhimen Hospital of the First Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100700, China

Molecules 2017, 22(5), 715; https://doi.org/10.3390/molecules22050715 - 29 Apr 2017

Cited by 55 | Viewed by 6413

Abstract

Nine monoterpenoids from Radix Paeoniae Alba, including paeoniflorin derivatives, paeoniflorin (PF), 4-O-methylpaeoniflorin (MPF), 4-O-methylbenzoylpaeoniflorin (MBPF); paeonidanin derivatives, paeonidanin (PD), paeonidanin A (PDA), albiflorin derivatives, albiflorin (AF), benzoylalbiflorin (BAF), galloylalbiflorin (GAF), and debenzoylalbiflorin (DAF), were obtained in our previous [...] Read more.

Nine monoterpenoids from Radix Paeoniae Alba, including paeoniflorin derivatives, paeoniflorin (PF), 4-O-methylpaeoniflorin (MPF), 4-O-methylbenzoylpaeoniflorin (MBPF); paeonidanin derivatives, paeonidanin (PD), paeonidanin A (PDA), albiflorin derivatives, albiflorin (AF), benzoylalbiflorin (BAF), galloylalbiflorin (GAF), and debenzoylalbiflorin (DAF), were obtained in our previous phytochemistry investigations. Their anti-inflammatory effects were determined in the present study. The expression and production of pro-inflammatory cytokines in lipopolysaccharides (LPS)-stimulated RAW 264.7 cells were measured using an Elisa assay and nitric oxide (NO) release was determined using the Griess method. The results demonstrated that the most of the monoterpenoids suppressed the LPS-induced production of NO, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). The anti-inflammatory activities of these monoterpenoids were closely related to their structural characteristics. Paeoniflorins and paeonidanins presented stronger anti-inflammatory activities than those of albiflorin derivatives. Furthermore, the action mechanisms of MBPF, having a strong anti-inflammatory effect, were investigated using quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot methods. The results indicated that MBPF could down-regulate the mRNA and protein expression level of inducible nitric oxide synthase (iNOS) in LPS-stimulated RAW 264.7 cells. The mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/AKT and nuclear factor κB (NF-κB) signaling pathways are involved in mediating the role of MBPF in suppressing the expression and production of pro-inflammatory cytokines in RAW 264.7 cells. Full article

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17 pages, 576 KiB

Open AccessFeature PaperArticle

Volatile Composition in Two Pummelo Cultivars (Citrus grandis L. Osbeck) from Different Cultivation Regions in China

by Mingxia Zhang^1,*, Linbo Li¹, Zhongwei Wu¹, Yanjie Wang¹, Yiming Zang² and Guojie Liu²

¹ School of Life Science and Technology, Henan Institute of Science and Technology, Xinxiang 453003, Henan, China

² College of Agriculture and Biotechnology, China Agriculture University, Yuanmingyuan Xilu, Beijing 10093, China

Molecules 2017, 22(5), 716; https://doi.org/10.3390/molecules22050716 - 29 Apr 2017

Cited by 16 | Viewed by 4755

Abstract

This study investigated the composition of volatile compounds in two pummelo cultivars, including ‘Shatian’ and ‘Guanxi’, cultivated in different regions of China with the aim of studying the effect of cultivar and cultivation condition on biosynthesis of volatile compounds in pummelo. Volatile compounds [...] Read more.

This study investigated the composition of volatile compounds in two pummelo cultivars, including ‘Shatian’ and ‘Guanxi’, cultivated in different regions of China with the aim of studying the effect of cultivar and cultivation condition on biosynthesis of volatile compounds in pummelo. Volatile compounds were extracted from pummelo juice using head-space microextraction and then analyzed using gas chromatography coupled with mass spectrometry. Results showed that a total of 49 volatile compounds was detected in the study, including 11 aldehydes, 7 alcohols, 3 ketones, 7 esters, 19 terpenes and 2 other volatiles. The ‘Guanxi’ pummelo cultivar possessed a more complex composition of volatile compounds compared with the ‘Shatian’ cultivar. Meanwhile, the volatile compounds appeared to exhibit a higher concentration in the ‘Guanxi’ cultivar samples than the ‘Shatian’ cultivar. Cluster analysis revealed that the ‘Guanxi’ cultivar samples from the different regions were grouped together, whereas the ‘Shatian’ cultivar samples were assembled. Principal component analysis showed that an obvious separation was observed between the ‘Guanxi’ and ‘Shatian’ cultivar. However, the ‘Shatian-SC15’ was significantly separated from the other ‘Shatian’ cultivar samples. These indicated that cultivar genotype was the primary factor that determined the volatile profile of the pummelo cultivar. Cultivation region might affect the biosynthesis of volatile compounds, resulting in the differentiation of the volatile composition in each pummelo cultivar. Full article

(This article belongs to the Section Molecular Diversity)

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10 pages, 1189 KiB

Open AccessArticle

Chemical Comparison of Two Drying Methods of Mountain Cultivated Ginseng by UPLC-QTOF-MS/MS and Multivariate Statistical Analysis

by Xin-fang Xu¹

, Shu-ya Xu¹, Ying Zhang¹, Hui Zhang¹, Meng-nan Liu¹, Huan Liu¹, Yan Gao¹, Xue Xue¹, Hui Xiong¹, Rui-chao Lin^1,2 and Xiang-ri Li^1,2,*

¹ School of Chinese Materia Medica, Beijing University of Chinese Medicine, No. 6 Wangjing zhonghuannan Road, Beijing 100102, China

² Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, No. 11 North Third Ring Road, Beijing 100029, China

Molecules 2017, 22(5), 717; https://doi.org/10.3390/molecules22050717 - 30 Apr 2017

Cited by 29 | Viewed by 6185

Abstract

In traditional Chinese medicine practice, drying method is an essential factor to influence the components of Chinese medicinal herbs. In this study, an ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS)-based approach was used to compare the content of chemical compounds of [...] Read more.

In traditional Chinese medicine practice, drying method is an essential factor to influence the components of Chinese medicinal herbs. In this study, an ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS)-based approach was used to compare the content of chemical compounds of mountain cultivated ginseng that had been natural air dried (LX-P) and vacuum freeze-dried (LX-L). Multivariate statistical analysis such as principal component analysis (PCA) and supervised orthogonal partial least squared discrimination analysis (OPLS-DA) were used to select the influential components of different samples. There were 41 ginsenosides unambiguously identified and tentatively assigned in both LX-L and LX-P. The results showed that the characteristic components in LX-P were ginsenoside Rb1, ginsenoside Rc, ginsenoside Rg6, dendrolasin, and ginsenoside Rb2. The characteristic components in LX-L were malonyl-ginsenoside Re, malonyl-ginsenoside Rb1, malonyl-ginsenoside Rc, malonyl-ginsenoside Rb1 isomer, malonyl-ginsenoside Rb2, malonyl-ginsenoside Rb3, malonyl-ginsenoside Rd isomer, gypenoside XVII, and notoginsenoside Fe. This is the first time that the differences between LX-L and LX-P have been observed systematically at the chemistry level. It was indicated that vacuum freeze-drying method can improve the content of malonyl-ginsensides in mountain cultivated ginseng. Full article

(This article belongs to the Special Issue Current Trends in Ginseng Research)

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17 pages, 1156 KiB

Open AccessArticle

Rapid Quantification and Quantitation of Alkaloids in Xinjiang Fritillaria by Ultra Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry

by Aziz Mohammat^1,3,4, Abulimiti Yili^1,2 and Haji Akber Aisa^1,2,*

¹ Key Laboratory of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China

² Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China

³ University of Chinese Academy of Sciences, Beijing 100039, China

⁴ Xinjiang Institute of Food and Drug Control, Urumqi 830000, China

Molecules 2017, 22(5), 719; https://doi.org/10.3390/molecules22050719 - 1 May 2017

Cited by 19 | Viewed by 5153

Abstract

The Fritillaria genus, including different kinds of medicinal and edible plants belonging to the Liliaceae family which have the function of treating and relieving a cough and eliminating phlegm, is widely planted in Xinjiang (China). There are few comprehensive studies reporting on the [...] Read more.

The Fritillaria genus, including different kinds of medicinal and edible plants belonging to the Liliaceae family which have the function of treating and relieving a cough and eliminating phlegm, is widely planted in Xinjiang (China). There are few comprehensive studies reporting on the characterization of the chemical constituents of Fritillaria from Xinjiang, and to date, no work describing the quantitative differences between the components in Fritillaria from Xinjiang and related species. The purpose of this study was to develop qualitative and quantitative analytical methods by Ultra Performance Liquid Chromatography-Quadrupole Time-of-flight Mass Spectrometry (UPLC-QTOF-MS) for the rapid quantification and quantitation of alkaloids in wild and cultivated Xinjiang Fritillaria, which could be used in the quality control of medicine based on this natural herb. Using the UPLC-QTOF-MS method, the chemical constituents of Xinjiang Fritillaria were identified by fragmentation information and retention behavior, and were compared to reference standards. Furthermore, a quantitative comparision of four major alkaloids in wild and cultivated Xinjiang Fritillaria was conducted by determining the content of Sipeimine-3β-d-glucoside, Sipeimine, Peimisine, and Yibeinoside A, respectively. A total of 89 characteristic peaks, including more than 40 alkaloids, were identified in the chromatographic results of Fritillaria. Four main alkaloids were quantified by using a validated method based on UPLC-QTOF-MS. The relative contents of Sipeimine-3β-d-glucoside, Sipeimine, Peimisine, and Yibeinoside A varied from 0.0013%~0.1357%, 0.0066%~0.1218%, 0.0033%~0.0437%, and 0.0019%~0.1398%, respectively. A rough separation of wild and cultivated Fritillaria could be achieved by the cluster analysis method. Full article

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11 pages, 1810 KiB

Open AccessArticle

Toward Exploring Novel Organic Materials: MP4-DFT Properties of 4-Amino-3-Iminoindene

by Tareq Irshaidat

Department of Chemistry, College of Sciences, Al-Hussein Bin Talal University, P. O. Box 20, Ma’an, Jordan

Molecules 2017, 22(5), 720; https://doi.org/10.3390/molecules22050720 - 30 Apr 2017

Cited by 5 | Viewed by 4113

Abstract

Tautomerism links with many applications and remains an attracting feature in exploring novel systems. In this regard, properties of indene-based HNCCCN segments have not received any considerable attention. In this computational organic chemistry study, first, to calculate the proton transfer energy barrier at [...] Read more.

Tautomerism links with many applications and remains an attracting feature in exploring novel systems. In this regard, properties of indene-based HNCCCN segments have not received any considerable attention. In this computational organic chemistry study, first, to calculate the proton transfer energy barrier at a reasonable cost, the study identified an accurate forth order Møller–Plesset perturbation theory-density functional theory (MP4-DFT) protocol equivalent to the outstanding pioneering benchmark calculations. The calculations illustrate that the two tautomers of the 4-amino-3-iminoindene nucleus are separated by a considerable energy barrier while featuring different molecular orbital characteristics; frontier orbital distribution, λmax, and energies, which are known basic requirements in molecular switching and logic circuit applications. The N-H/BH₂ substitution was found to have significant influence on the electronic structure of the skeleton. Similarities in the two tautomers and the boron derivative to properties of known molecular materials have been found. Full article

(This article belongs to the Section Computational and Theoretical Chemistry)

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14 pages, 18225 KiB

Open AccessArticle

One-Step Synthesis of Silver Nanoparticles on Polydopamine-Coated Sericin/Polyvinyl Alcohol Composite Films for Potential Antimicrobial Applications

by Rui Cai¹, Gang Tao², Huawei He²

, Kai Song², Hua Zuo³, Wenchao Jiang² and Yejing Wang^1,*

¹ College of Biotechnology, Southwest University, Beibei, Chongqing 400715, China

² State Key Laboratory of Silkworm Genome Biology, Southwest University, Beibei, Chongqing 400715, China

³ College of Pharmaceutical Sciences, Southwest University, Beibei, Chongqing 400715, China

Molecules 2017, 22(5), 721; https://doi.org/10.3390/molecules22050721 - 30 Apr 2017

Cited by 58 | Viewed by 12254

Abstract

Silk sericin has great potential as a biomaterial for biomedical applications due to its good hydrophilicity, reactivity, and biodegradability. To develop multifunctional sericin materials for potential antibacterial application, a one-step synthesis method for preparing silver nanoparticles (AgNPs) modified on polydopamine-coated sericin/polyvinyl alcohol (PVA) [...] Read more.

Silk sericin has great potential as a biomaterial for biomedical applications due to its good hydrophilicity, reactivity, and biodegradability. To develop multifunctional sericin materials for potential antibacterial application, a one-step synthesis method for preparing silver nanoparticles (AgNPs) modified on polydopamine-coated sericin/polyvinyl alcohol (PVA) composite films was developed. Polydopamine (PDA) acted as both metal ion chelating and reducing agent to synthesize AgNPs in situ on the sericin/PVA composite film. Scanning electron microscopy and energy dispersive spectroscopy analysis revealed that polydopamine could effectively facilitate the high-density growth of AgNPs as a 3-D matrix. X-ray diffractometry studies suggested the synthesized AgNPs formed good face-centered cubic crystalline structures. Contact angle measurement and mechanical test indicated AgNPs modified PDA-sericin/PVA composite film had good hydrophilicity and mechanical property. The bacterial growth curve and inhibition zone assays showed the AgNPs modified PDA-sericin/PVA composite film had long-term antibacterial activities. This work develops a new method for the preparation of AgNPs modified PDA-sericin/PVA film with good hydrophilicity, mechanical performance and antibacterial activities for the potential antimicrobial application in biomedicine. Full article

(This article belongs to the Special Issue Antibacterial Materials and Coatings)

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12 pages, 4197 KiB

Open AccessArticle

Hibiscus sabdariffa L. and Its Bioactive Constituents Exhibit Antiviral Activity against HSV-2 and Anti-enzymatic Properties against Urease by an ESI-MS Based Assay

by Sherif T. S. Hassan^1,2,*

, Emil Švajdlenka¹ and Kateřina Berchová-Bímová²

¹ Department of Natural Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackého tř. 1946/1, 612 42 Brno, Czech Republic

² Department of Applied Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamýcká 129, 165 21 Praha-Suchdol, Czech Republic

Molecules 2017, 22(5), 722; https://doi.org/10.3390/molecules22050722 - 30 Apr 2017

Cited by 41 | Viewed by 7586

Abstract

For decades, Hibiscus sabdariffa L. and its phytochemicals have been shown to possess a wide range of pharmacologic properties. In this study, aqueous extract of Hibiscus sabdariffa (AEHS) and its bioactive constituent protocatechuic acid (PCA), have been evaluated in vitro for their antiviral [...] Read more.

For decades, Hibiscus sabdariffa L. and its phytochemicals have been shown to possess a wide range of pharmacologic properties. In this study, aqueous extract of Hibiscus sabdariffa (AEHS) and its bioactive constituent protocatechuic acid (PCA), have been evaluated in vitro for their antiviral activity against HSV-2 clinical isolates and anti-enzymatic activity against urease. Antiherpetic activity was evaluated by the titer reduction assay in infected Vero cells, and cytotoxicity was evaluated by the neutral red dye-uptake method. Anti-urease activity was determined by a developed Electrospray Ionization-Mass Spectrometry (ESI-MS)-based assay. PCA showed potent anti-HSV-2 activity compared with that of acyclovir, with EC₅₀ values of 0.92 and 1.43 µg∙mL⁻¹, respectively, and selectivity indices > 217 and > 140, respectively. For the first time, AEHS was shown to exert anti-urease inhibition activity, with an IC₅₀ value of 82.4 µg∙mL⁻¹. This, combined with its safety, could facilitate its use in practical applications as a natural urease inhibitor. Our results present Hibiscus sabdariffa L. and its bioactive compound PCA as potential therapeutic agents in the treatment of HSV-2 infection and the treatment of diseases caused by urease-producing bacteria. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 885 KiB

Open AccessArticle

Rhodium(I)-Complexes Catalyzed 1,4-Conjugate Addition of Arylzinc Chlorides to N-Boc-4-pyridone

by Fenghai Guo^1,*

, Matthew A. McGilvary¹, Malcolm C. Jeffries¹, Briana N. Graves¹, Shekinah A. Graham¹ and Yuelin Wu²

¹ Department of Chemistry, Winston-Salem State University, Winston Salem, NC 27110, USA

² School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China

Molecules 2017, 22(5), 723; https://doi.org/10.3390/molecules22050723 - 1 May 2017

Cited by 1 | Viewed by 6360

Abstract

Rhodium(I)-complexes catalyzed the 1,4-conjugate addition of arylzinc chlorides to N-Boc-4-pyridone in the presence of chlorotrimethylsilane (TMSCl). A combination of [RhCl(C₂H₄)₂]₂ and BINAP was determined to be the most effective catalyst to promote the 1,4-conjugate addition [...] Read more.

Rhodium(I)-complexes catalyzed the 1,4-conjugate addition of arylzinc chlorides to N-Boc-4-pyridone in the presence of chlorotrimethylsilane (TMSCl). A combination of [RhCl(C₂H₄)₂]₂ and BINAP was determined to be the most effective catalyst to promote the 1,4-conjugate addition reactions of arylzinc chlorides to N-Boc-4-pyridone. A broad scope of arylzinc reagents with both electron-withdrawing and electron-donating substituents on the aromatic ring successfully underwent 1,4-conjugate addition to N-Boc-4-pyridone to afford versatile 1,4-adducts 2-substituted-2,3-dihydropyridones in good to excellent yields (up to 91%) and excellent ee (up to 96%) when (S)-BINAP was used as chiral ligand. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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8 pages, 1029 KiB

Open AccessArticle

Quasi-Living Polymerization of Propene with an Isotactic-Specific Zirconocene Catalyst

by Kei Nishii¹, Miyuki Murase² and Takeshi Shiono^3,*

¹ Department of Materials Chemistry and Bioengineering, National Institute of Technology, Oyama College, 771 Nakakuki, Oyama, Tochigi 323-0806, Japan

² Japan Polypropylene Corporation Polymerization Technical Center 1 Toho-cho, Yokkaichi, Mie 510-0848, Japan

³ Department of Applied Chemistry, Graduate School of Engineering, Hiroshima University, Higashi-Hiroshima 739-8527, Japan

Molecules 2017, 22(5), 725; https://doi.org/10.3390/molecules22050725 - 2 May 2017

Cited by 1 | Viewed by 4961

Abstract

Propene polymerization with isotactic (iso)-specific C₂-symmetric rac-Me₂Si(2-Me-Benz(e)-Ind)₂ZrCl₂ (1) and rac-Me₂Si(2-Me-4-Ph-1-Ind)₂ZrCl₂ (2) were conducted under various conditions for achieving iso-specific living polymerization of [...] Read more.

Propene polymerization with isotactic (iso)-specific C₂-symmetric rac-Me₂Si(2-Me-Benz(e)-Ind)₂ZrCl₂ (1) and rac-Me₂Si(2-Me-4-Ph-1-Ind)₂ZrCl₂ (2) were conducted under various conditions for achieving iso-specific living polymerization of propene. When Complex 1 was activated with trialkylaluminum-free modified methylaluminoxane (dMMAO) at −40 °C, the number-average molecular weight (M_n) linearly increased against the polymerization time to reach M_n = 704,000 within 15 min of polymerization, although the molecular weight distributions was broad (M_w/M_n < 3). Thus, it was found that quasi-living polymerization of propene proceeded in the 1-dMMAO system. The living nature of iso-polypropene was confirmed by the block copolymerization, where the M_n value increased from 221,000 to 382,000 after the addition of 1-octene to yield the block copolymer with a melting point of 150 °C. Full article

(This article belongs to the Special Issue Organometallic Catalysis for Olefin Polymerization/Oligomerization)

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16 pages, 979 KiB

Open AccessArticle

Effects of Copper Pollution on the Phenolic Compound Content, Color, and Antioxidant Activity of Wine

by Xiangyu Sun, Tingting Ma, Luyang Han, Weidong Huang and Jicheng Zhan^*

College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing 100083, China

Molecules 2017, 22(5), 726; https://doi.org/10.3390/molecules22050726 - 3 May 2017

Cited by 37 | Viewed by 6599

Abstract

The effects of copper pollution on the polyphenol content, color, and antioxidant activity of wine, as well as correlations among these factors, were investigated. Copper had clear influences on wine polyphenol content. At low copper concentrations, the concentrations of nearly all polyphenols increased, [...] Read more.

The effects of copper pollution on the polyphenol content, color, and antioxidant activity of wine, as well as correlations among these factors, were investigated. Copper had clear influences on wine polyphenol content. At low copper concentrations, the concentrations of nearly all polyphenols increased, and the antioxidant activity values of the wine also increased. When the copper concentration reached the lowest level of the medium copper range (9.6~16 mg/L), most of the indices also improved. When the copper concentrations reached the latter part of the medium copper range (19.2 and 22.4 mg/L), many of the tested indices began to decrease. Furthermore, when the copper concentration reached the high ranges (32, 64, and 96 mg/L), the polyphenol content, CIELAB color parameters, and antioxidant activity of wine were substantially decreased, indicating the need to control increasing copper content in grape must. Full article

(This article belongs to the Collection Wine Chemistry)

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8 pages, 2213 KiB

Open AccessArticle

Acetylcholinesterase Inhibitory Meroterpenoid from a Mangrove Endophytic Fungus Aspergillus sp. 16-5c

by Yuhua Long^1,2, Hui Cui¹, Xinglie Liu³, Ze’en Xiao¹, Shitong Wen², Zhigang She¹ and Xishan Huang^1,*

¹ School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, China

² School of Chemistry and Environment, South China Normal University, Guangzhou 510006, China

³ The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510275, China

Molecules 2017, 22(5), 727; https://doi.org/10.3390/molecules22050727 - 3 May 2017

Cited by 37 | Viewed by 5287

Abstract

One new meroterpenoid, named 2-hydroacetoxydehydroaustin (1), together with nine known meroterpenoids, 11-acetoxyisoaustinone (2), isoaustinol (3), austin (4), austinol (5), acetoxydehydroaustin (6), dehydroaustin (7), dehydroaustinol (8), preaustinoid A2 [...] Read more.

One new meroterpenoid, named 2-hydroacetoxydehydroaustin (1), together with nine known meroterpenoids, 11-acetoxyisoaustinone (2), isoaustinol (3), austin (4), austinol (5), acetoxydehydroaustin (6), dehydroaustin (7), dehydroaustinol (8), preaustinoid A2 (9), and 1,2-dihydro-acetoxydehydroaustin B (10), were isolated from the mangrove endophytic fungus, Aspergillus sp. 16-5c. These structures were characterized by spectroscopic analysis, further the absolute configurations of stereogenic carbons for Compounds 1, 3, 4, 6, 7, 8, 9, and 10 were determined by single crystal X-ray diffraction analysis using Cu Kα radiation. Moreover, the absolute configurations of stereogenic carbons for Known Compounds 3, 7, 8, and 9 are identified here for the first time. Compounds 3, 7, and 8 showed acetylcholinesterase (AchE) inhibitory activity with IC₅₀ values of 2.50, 0.40, and 3.00 μM, respectively. Full article

(This article belongs to the Special Issue Metabolites of Terrestrial and Marine Origin on the Age-Related Disorders)

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10 pages, 2338 KiB

Open AccessArticle

The Impact of the Low Molecular Weight Heparin Tinzaparin on the Sensitization of Cisplatin-Resistant Ovarian Cancers—Preclinical In Vivo Evaluation in Xenograft Tumor Models

by Thomas Mueller¹

, Daniel Bastian Pfankuchen², Kathleen Wantoch von Rekowski², Martin Schlesinger², Franziska Reipsch¹ and Gerd Bendas^2,*

¹ Department of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Straße 40, 06120 Halle (Saale), Germany

² Department of Pharmacy, University Bonn, An der Immenburg 4, 53121 Bonn, Germany

Molecules 2017, 22(5), 728; https://doi.org/10.3390/molecules22050728 - 3 May 2017

Cited by 16 | Viewed by 5934

Abstract

Resistance formation of tumors against chemotherapeutics is the major obstacle in clinical cancer therapy. Although low molecular weight heparin (LMWH) is an important component in oncology referring to guideline-based antithrombotic prophylaxis of tumor patients, a potential interference of LMWH with chemoresistance is unknown. [...] Read more.

Resistance formation of tumors against chemotherapeutics is the major obstacle in clinical cancer therapy. Although low molecular weight heparin (LMWH) is an important component in oncology referring to guideline-based antithrombotic prophylaxis of tumor patients, a potential interference of LMWH with chemoresistance is unknown. We have recently shown that LMWH reverses the cisplatin resistance of A2780cis human ovarian cancer cells in vitro. Here we address the question whether this LMWH effect is also valid under in vivo conditions. Therefore, we established tumor xenografts of A2780 and cisplatin resistant A2780cis cells in nude mice and investigated the impact of daily tinzaparin applications (10 mg/kg BW) on anti-tumor activity of cisplatin (6 mg/kg BW, weekly) considering the tumor growth kinetics. Intratumoral platinum accumulation was detected by GF-AAS. Xenografts of A2780 and A2780cis cells strongly differed in cisplatin sensitivity. As an overall consideration, tinzaparin co-treatment affected the response to cisplatin of A2780cis, but not A2780 tumors in the later experimental time range. A subgroup analysis confirmed that initially smaller A2780cis tumors benefit from tinzaparin, but also small A2780 xenografts. Tinzaparin did not affect cisplatin accumulation in A2780cis xenografts, but strongly increased the platinum content in A2780, obviously related to morphological differences in both xenografts. Although we cannot directly confirm a return of A2780cis cisplatin resistance by tinzaparin, as shown in vitro, the present findings give reason to discuss heparin effects on cytostatic drug efficiency for small tumors and warrants further investigation. Full article

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

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10 pages, 1141 KiB

Open AccessArticle

Assessing Scaffold Diversity of Kinase Inhibitors Using Alternative Scaffold Concepts and Estimating the Scaffold Hopping Potential for Different Kinases

by Dilyana Dimova

and Jürgen Bajorath^*

Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Dahlmannstr. 2, Bonn D-53113, Germany

Molecules 2017, 22(5), 730; https://doi.org/10.3390/molecules22050730 - 3 May 2017

Cited by 14 | Viewed by 7239

Abstract

Publicly available kinase inhibitors provide a large source of information for structure–activity relationship analysis and kinase drug design. In this study, publicly available inhibitors of the human kinome were collected and analog series formed by kinase inhibitors systematically identified. Then, alternative scaffold concepts [...] Read more.

Publicly available kinase inhibitors provide a large source of information for structure–activity relationship analysis and kinase drug design. In this study, publicly available inhibitors of the human kinome were collected and analog series formed by kinase inhibitors systematically identified. Then, alternative scaffold concepts were applied to assess diversity and promiscuity of kinase inhibitors. Over the past two years, the number of publicly available kinase inhibitors with high-confidence activity data more than doubled, but coverage of the human kinome only slightly increased. Approximately 70% of current kinase inhibitors belonged to analog series. However, the detectable degree of promiscuity among these kinase inhibitors remained low. Approximately 76% of all inhibitors were only annotated with a single kinase, compared to ~70% two years ago. For many kinases, the assessment of scaffold diversity among their inhibitors and the distribution of differently defined scaffolds over analog series made it possible to assess scaffold hopping potential. Our analysis revealed that the consideration of conventional compound-based scaffolds most likely leads to an overestimation of scaffold hopping frequency, at least for compounds forming analog series. Full article

(This article belongs to the Special Issue Kinase Inhibitors)

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9 pages, 1369 KiB

Open AccessArticle

Template Effect of the Graphene Moiré Lattice on Phthalocyanine Assembly

by Nicolas Néel^* and Jörg Kröger

Institut für Physik, Technische Universität Ilmenau, D-98693 Ilmenau, Germany

Molecules 2017, 22(5), 731; https://doi.org/10.3390/molecules22050731 - 3 May 2017

Cited by 7 | Viewed by 7765

Abstract

Superstructures of metal-free phthalocyanine (2H-Pc) molecules on graphene-covered Ir(111) have been explored by scanning tunnelling microscopy. Depending on the sub-monolayer coverage different molecular assemblies form at the surface. They reflect the transition from a graphene template effect on the 2H-Pc arrangement to molecular [...] Read more.

Superstructures of metal-free phthalocyanine (2H-Pc) molecules on graphene-covered Ir(111) have been explored by scanning tunnelling microscopy. Depending on the sub-monolayer coverage different molecular assemblies form at the surface. They reflect the transition from a graphene template effect on the 2H-Pc arrangement to molecular superstructures that are mainly governed by the intermolecular coupling. Full article

(This article belongs to the Special Issue Porphyrins and Phthalocyanines: Synthesis, Properties and Applications)

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13 pages, 6336 KiB

Open AccessArticle

Brazilian Green Propolis Extract Synergizes with Protoporphyrin IX-mediated Photodynamic Therapy via Enhancement of Intracellular Accumulation of Protoporphyrin IX and Attenuation of NF-κB and COX-2

by Cheng-Cheng Wang^1,†, Yu-Xuan Wang^2,†, Nian-Qin Yu³, Die Hu³, Xiao-Yan Wang³, Xing-Guang Chen³, You-Wei Liao³, Jing Yao^3,4,5, Hao Wang^3,4,5, Ling He^6,* and Liang Wu^3,*

¹ School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China

² School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China

³ Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China

⁴ State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China

⁵ Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China

⁶ Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China

^† These authors contributed equally to this work and should be considered co-first authors.

Molecules 2017, 22(5), 732; https://doi.org/10.3390/molecules22050732 - 4 May 2017

Cited by 25 | Viewed by 6904

Abstract

Brazilian green propolis (BGP) is noted for its impressive antitumor effects and has been used as a folk medicine in various cultures for many years. It has been demonstrated that BGP could enhance the cytotoxic effect of cytostatic drugs on tumor cells. Photodynamic [...] Read more.

Brazilian green propolis (BGP) is noted for its impressive antitumor effects and has been used as a folk medicine in various cultures for many years. It has been demonstrated that BGP could enhance the cytotoxic effect of cytostatic drugs on tumor cells. Photodynamic therapy (PDT) is a therapeutic approach used against malignant cells. To assess the synergistic effect of BGP extract on protoporphyrin IX (PpIX)-mediated photocytotoxicity, MTT assays were performed using A431 and HeLa cells. TUNEL assay and Annexin V-FITC/PI staining were performed to confirm the induction of apoptosis. Western blotting analysis was performed to examine the pro-apoptotic proteins, anti-apoptotic proteins and inflammation related proteins in A431 cells. Intracellular accumulation of PpIX was examined by flow cytometry. The synergistic effect of BGP extract in PpIX-PDT was also evaluated with a xenograft model. Our findings reveal that BGP extract increased PpIX-mediated photocytotoxicity in A431 and HeLa cells. PpIX-PDT with BGP extract treatment resulted in a decrease in Bcl-xL and an increase in NOXA, Bax and caspase-3 cleavage. The protein expression levels of p-IKKα/β, NF-κB and COX-2 were upregulated by PpIX-PDT but significantly attenuated when in combination with BGP extract. BGP extract was also found to significantly enhance the intracellular accumulation of PpIX in A431 cells. BGP extract increased PpIX-mediated photocytotoxicity in a xenograft model as well. Our findings provide evidence for a synergistic effect of BGP extract in PpIX-PDT both in vitro and in vivo. Full article

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12 pages, 1759 KiB

Open AccessArticle

In Vitro Glucuronidation and Sulfation of ε-Viniferin, a Resveratrol Dimer, in Humans and Rats

by Arnaud Courtois^1,2,3,†

, Michael Jourdes^1,2,†, Adeline Dupin^1,2, Caroline Lapèze^1,2, Elodie Renouf^1,4, Benoît Biais¹, Pierre-Louis Teissedre^1,2, Jean-Michel Mérillon^1,2,4, Tristan Richard^1,2 and Stéphanie Krisa^1,2,*

¹ Unité de Recherche Œnologie, Molécules d’Intérêt Biologique, EA 4577, USC 1366 INRA, Bordeaux INP, Institut des Sciences de la Vigne et du Vin, 210 Chemin de Leysottes, 33882 Villenave d’Ornon, France

² Université de Bordeaux, 146, rue Léo Saignat, 33076 Bordeaux, France

³ Centre Antipoison et de Toxicovigilance d’Aquitaine Poitou-Charentes, Bâtiment UNDR, CHU de Bordeaux, Place Amélie Raba Léon, 33076 Bordeaux, France

⁴ Polyphénols Biotech, Université de Bordeaux, Institut des Sciences de la Vigne et du Vin, 210 Chemin de Leysottes, 33882 Villenave d’Ornon, France

^† These authors contributed equally to the paper.

Molecules 2017, 22(5), 733; https://doi.org/10.3390/molecules22050733 - 3 May 2017

Cited by 19 | Viewed by 6443

Abstract

ε-Viniferin is a resveratrol dimer that possesses antioxidant or anti-inflammatory activities. However little is known about the metabolism of this oligostilbene. This study was thus undertaken as a first approach to identify and characterize the metabolites of ε-viniferin and to describe the kinetic [...] Read more.

ε-Viniferin is a resveratrol dimer that possesses antioxidant or anti-inflammatory activities. However little is known about the metabolism of this oligostilbene. This study was thus undertaken as a first approach to identify and characterize the metabolites of ε-viniferin and to describe the kinetic profile of their appearance in humans and rats. The glucuronides and sulfates of ε-viniferin were first obtained by chemical hemi-synthesis and were fully characterized by UPLC-MS and NMR spectroscopy. Then, ε-viniferin was incubated with human or rat S9 liver fractions that led to the formation of four glucuronoconjugates and four sulfoconjugates. In both species, ε-viniferin was subjected to an intense metabolism as 70 to 80% of the molecule was converted to glucuronides and sulfates. In humans, the hepatic clearance of ε-viniferin (V_max/K_m) for glucuronidation and sulfation were 4.98 and 6.35 µL/min/mg protein, respectively, whereas, in rats, the hepatic clearance for glucuronidation was 20.08 vs. 2.59 µL/min/mg protein for sulfation. In humans, three major metabolites were observed: two glucuronides and one sulfate. By contrast, only one major glucuronide was observed in rats. This strong hepatic clearance of ε-viniferin in human and rat could explain its poor bioavailability and could help to characterize its active metabolites. Full article

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

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15 pages, 1229 KiB

Open AccessArticle

Dynamic Changes in Neutral and Acidic Ginsenosides with Different Cultivation Ages and Harvest Seasons: Identification of Chemical Characteristics for Panax ginseng Quality Control

by Zhi Liu^1,2,3, Chong-Zhi Wang³, Xing-You Zhu⁴, Jin-Yi Wan³, Jing Zhang², Wei Li^2,*

, Chang-Chun Ruan^1,* and Chun-Su Yuan³

¹ Institute of Agricultural Modernization, Jilin Agricultural University, Changchun 130118, China

² College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China

³ Tang Center for Herbal Medicine Research and The Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA

⁴ Jinlin Provincial Sericulture Institute, Jilin 132012, China

Molecules 2017, 22(5), 734; https://doi.org/10.3390/molecules22050734 - 4 May 2017

Cited by 57 | Viewed by 7939

Abstract

In this study, dynamic changes in ginsenoside content and ratios in the Panax ginseng root were investigated with different cultivation ages and different collection months, using high-performance liquid chromatography (HPLC). Our data indicate that changes in ginsenoside Ro and malonyl ginsenosides content were [...] Read more.

In this study, dynamic changes in ginsenoside content and ratios in the Panax ginseng root were investigated with different cultivation ages and different collection months, using high-performance liquid chromatography (HPLC). Our data indicate that changes in ginsenoside Ro and malonyl ginsenosides content were dependent on the ginseng cultivation age (p < 0.05); especially, the Ro content varied from 0.16 to 4.91 mg/g, with a difference about 30-fold. Further, we found that the samples of 5 and 6-year-old P. ginseng had high Ro/Re ratio, whereas two and three-year-old P. ginseng possessed low Ro/Re ratio. Thus, the Ro/Re ratio can be used as a characteristic marker for differentiating the age of the root. The relative content of ginsenosides Rg₁ and Re were affected by the ginseng’s harvest season. The Re content was higher than the Rg₁ content in May and June, but lower than the Rg₁ content from August to October. Thus, the Rg₁/Re ratio can be used as a characteristic marker for differentiating the ginseng’s harvest seasons. These results indicate that the chemical characteristics of P. ginseng at different cultivation ages and harvest seasons are clearly different, which may cause differences in pharmacological activities and therapeutic effects. In addition, we developed HPLC coupled with hierarchical cluster analysis and principal component analysis methods to identify the cultivation age and harvest season of P. ginseng using characteristic ginsenosides. Our results showed that this method can be used to discriminate the cultivation age and harvest season of P. ginseng. Full article

(This article belongs to the Special Issue Current Trends in Ginseng Research)

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13 pages, 2562 KiB

Open AccessArticle

Characterization of Chinese Unifloral Honeys Based on Proline and Phenolic Content as Markers of Botanical Origin, Using Multivariate Analysis

by Ya-Qin Wen^1,2,3, Jinzhen Zhang^1,2,3,4, Yi Li^1,2,3,4, Lanzhen Chen^1,2,3,4, Wen Zhao^1,2,3,4, Jinhui Zhou^1,2,3,4,* and Yue Jin^1,2,3,4,*

¹ Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing 100093, China

² Bee Product Quality Supervision and Testing Center, Ministry of Agriculture, Beijing 100093, China

³ Laboratory of Risk Assessment for Quality and Safety of Bee Products, Ministry of Agriculture, Beijing 100093, China

⁴ Key Laboratory of Bee Products for Quality and Safety Control, Ministry of Agriculture, Beijing 100093, China

Molecules 2017, 22(5), 735; https://doi.org/10.3390/molecules22050735 - 17 May 2017

Cited by 35 | Viewed by 6043

Abstract

The phenolic and proline content were determined in honey samples of different floral origins (rapeseed, sunflower, buckwheat and Codonopsis) from five different regions of China. The phenolic and proline profile of these samples were used to construct a statistical model to distinguish [...] Read more.

The phenolic and proline content were determined in honey samples of different floral origins (rapeseed, sunflower, buckwheat and Codonopsis) from five different regions of China. The phenolic and proline profile of these samples were used to construct a statistical model to distinguish honeys from different floral origins. Significant differences were identified among the studied honey samples from multivariate chemometric methods. The proline content varied among the four types of honeys, with the values decreasing in the order: buckwheat > Codonopsis > sunflower > rapeseed. Rapeseed honeys contained a high level of benzoic acid, while rutin, p-coumaric acid, p-hydroxybenzoic acid were present at relatively high levels in buckwheat honeys. Principal component analysis (PCA) revealed that rapeseed honey could be distinguished from the other three unifloral honeys, and benzoic acid, proline and kaempferol could serve as potential floral markers. Using 18 phenolic compounds and proline the honey samples were satisfactorily classified according to floral origin at 94% correct prediction by linear discriminant analysis (LDA). The results indicated that phenolic compounds and proline were useful for the identification of the floral origin of the four type honeys. Full article

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12 pages, 1705 KiB

Open AccessArticle

Ontogenetic Variation of Individual and Total Capsaicinoids in Malagueta Peppers (Capsicum frutescens) during Fruit Maturation

by Oreto Fayos¹, Ana Carolina De Aguiar², Ana Jiménez-Cantizano³, Marta Ferreiro-González⁴

, Ana Garcés-Claver¹

, Julián Martínez², Cristina Mallor¹

, Ana Ruiz-Rodríguez⁴, Miguel Palma⁴, Carmelo G. Barroso⁴ and Gerardo F. Barbero^4,*

¹ Agrifood Research Centre of Aragón (CITA), Montañana Avenue, 930, 50059 Zaragoza, Spain

² Department of Food Engineering, College of Food Engineering, University of Campinas, DEA/FEA/UNICAMP, Campinas 13083-862, SP, Brazil

³ Department of Chemical Engineering and Food Technology, Faculty of Sciences, University of Cádiz, Agrifood Campus of International Excellence (CeiA3), IVAGRO, P.O. Box 40, 11510 Puerto Real, Cádiz, Spain

⁴ Department of Analytical Chemistry, Faculty of Sciences, University of Cádiz, Agrifood Campus of International Excellence (CeiA3), IVAGRO, P.O. Box 40, 11510 Puerto Real, Cádiz, Spain

Molecules 2017, 22(5), 736; https://doi.org/10.3390/molecules22050736 - 3 May 2017

Cited by 28 | Viewed by 8052

Abstract

The ontogenetic variation of total and individual capsaicinoids (nordihydrocapsaicin (n-DHC), capsaicin (C), dihydrocapsaicin (DHC), homocapsaicin (h-C) and homodihydrocapsaicin (h-DHC)) present in Malagueta pepper (Capsicum frutescens) during fruit ripening has been studied. Malagueta peppers were grown in a greenhouse under controlled temperature [...] Read more.

The ontogenetic variation of total and individual capsaicinoids (nordihydrocapsaicin (n-DHC), capsaicin (C), dihydrocapsaicin (DHC), homocapsaicin (h-C) and homodihydrocapsaicin (h-DHC)) present in Malagueta pepper (Capsicum frutescens) during fruit ripening has been studied. Malagueta peppers were grown in a greenhouse under controlled temperature and humidity conditions. Capsaicinoids were extracted using ultrasound-assisted extraction (UAE) and the extracts were analyzed by ultra-performance liquid chromatography (UHPLC) with fluorescence detection. A significant increase in the total content of capsaicinoids was observed in the early days (between 12 and 33). Between day 33 and 40 there was a slight reduction in the total capsaicinoid content (3.3% decrease). C was the major capsaicinoid, followed by DHC, n-DHC, h-C and h-DHC. By considering the evolution of standardized values of the capsaicinoids it was verified that n-DHC, DHC and h-DHC (dihydrocapsaicin-like capsaicinoids) present a similar behavior pattern, while h-C and C (capsaicin-like capsaicinoids) show different evolution patterns. Full article

(This article belongs to the Collection Bioactive Compounds)

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11 pages, 4335 KiB

Open AccessArticle

Synthesis, Crystal Structures and Properties of Ferrocenyl Bis-Amide Derivatives Yielded via the Ugi Four-Component Reaction

by Mei Zhao, Guang-Kui Shao, Dan-Dan Huang, Xue-Xin Lv and Dian-Shun Guo^*

College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Shandong Normal University, Jinan 250014, China

Molecules 2017, 22(5), 737; https://doi.org/10.3390/molecules22050737 - 4 May 2017

Cited by 6 | Viewed by 4656

Abstract

Ten ferrocenyl bis-amide derivatives were successfully synthesized via the Ugi four-component reaction by treating ferrocenecarboxylic acid with diverse aldehydes, amines, and isocyanides in methanol solution. Their chemical structures were fully characterized by IR, NMR, HR-MS, and X-ray diffraction analyses. They feature unique molecular [...] Read more.

Ten ferrocenyl bis-amide derivatives were successfully synthesized via the Ugi four-component reaction by treating ferrocenecarboxylic acid with diverse aldehydes, amines, and isocyanides in methanol solution. Their chemical structures were fully characterized by IR, NMR, HR-MS, and X-ray diffraction analyses. They feature unique molecular morphologies and create a 14-membered ring motif in the centro-symmetric dimers generated in the solid state. Moreover, the electrochemical behavior of these ferrocenyl bis-amides was assessed by cyclic voltammetry. Full article

(This article belongs to the Section Organic Chemistry)

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18 pages, 851 KiB

Open AccessArticle

Design, Synthesis and Fungicidal Activity of 2-Substituted Phenyl-2-oxo-, 2-Hydroxy- and 2-Acyloxyethylsulfonamides

by Minlong Wang^1,†, Peng Rui^1,†, Caixiu Liu¹, Ying Du¹, Peiwen Qin¹, Zhiqiu Qi¹, Mingshan Ji¹, Xinghai Li^1,* and Zining Cui^2,3,*

¹ Department of Pesticide Science, Plant Protection College, Shenyang Agricultural University, Shenyang 110866, 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 Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, China

^† These authors contributed equally to this work.

Molecules 2017, 22(5), 738; https://doi.org/10.3390/molecules22050738 - 4 May 2017

Cited by 15 | Viewed by 5581

Abstract

Sulfonyl-containing compounds, which exhibit a broad spectrum of biological activities, comprise a substantial proportion of and play a vital role, not only in medicines but also in agrochemicals. As a result increasing attention has been paid to the research and development of sulfonyl [...] Read more.

Sulfonyl-containing compounds, which exhibit a broad spectrum of biological activities, comprise a substantial proportion of and play a vital role, not only in medicines but also in agrochemicals. As a result increasing attention has been paid to the research and development of sulfonyl derivatives. A series of thirty-eight 2-substituted phenyl-2-oxo- III, 2-hydroxy- IV and 2-acyloxyethylsulfonamides V were obtained and their structures confirmed by IR, ¹H-NMR, and elemental analysis. The in vitro and in vivo bioactivities against two Botrytis cinerea strains, DL-11 and HLD-15, which differ in their sensitivity to procymidone, were evaluated. The in vitro activity results showed that the EC₅₀ values of compounds V-1 and V-9 were 0.10, 0.01 mg L⁻¹ against the sensitive strain DL-11 and 3.32, 7.72 mg L⁻¹ against the resistant strain HLD-15, respectively. For in vivo activity against B. cinerea, compound V-13 and V-14 showed better control effect than the commercial fungicides procymidone and pyrimethanil. The further in vitro bioassay showed that compounds III, IV and V had broad fungicidal spectra against different phytopathogenic fungi. Most of the title compounds showed high fungicidal activities, which could be used as lead compounds for further developing novel fungicidal compounds against Botrytis cinerea. Full article

(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)

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14 pages, 1523 KiB

Open AccessArticle

The Combined Use of Schizosaccharomyces pombe and Lachancea thermotolerans—Effect on the Anthocyanin Wine Composition

by Ángel Benito, Fernando Calderón and Santiago Benito^*

Departamento de Química y Tecnología de Alimentos, Universidad Politécnica de Madrid, Ciudad Universitaria S/N, 28040 Madrid, Spain

Molecules 2017, 22(5), 739; https://doi.org/10.3390/molecules22050739 - 4 May 2017

Cited by 67 | Viewed by 7637

Abstract

The most popular methodology to make red wine is through the combined use of Saccharomyces cerevisiae yeast and lactic acid bacteria, for alcoholic fermentation and malolactic fermentation respectively. This classic winemaking practice produces stable red wines from a microbiological point of view. This [...] Read more.

The most popular methodology to make red wine is through the combined use of Saccharomyces cerevisiae yeast and lactic acid bacteria, for alcoholic fermentation and malolactic fermentation respectively. This classic winemaking practice produces stable red wines from a microbiological point of view. This study aims to investigate a recent red winemaking biotechnology, which through the combined use of Lachancea thermotolerans and Schizosaccharomyces pombe is used as an alternative to the classic malolactic fermentation. In this new methodology, Schizosaccharomyces pombe totally consumes malic acid, while Lachancea thermotolerans produces lactic acid, avoiding excessive deacidification of musts with low acidity in warm viticulture areas such as Spain. This new methodology has been reported to be a positive alternative to malolactic fermentation in low acidity wines, since it has the advantage to produce wines with a more fruity flavor, less acetic acid, less ethyl carbamate originators and less biogenic amines than the traditional wines produced via conventional fermentation techniques. The study focuses on unexplored facts related to this novel biotechnology such as color and anthocyanin profile. Full article

(This article belongs to the Collection Wine Chemistry)

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8 pages, 2298 KiB

Open AccessArticle

Off-Center Rotation of CuPc Molecular Rotor on a Bi(111) Surface and the Chiral Feature

by Kai Sun

, Min-Long Tao, Yu-Bing Tu and Jun-Zhong Wang^*

School of Physical Science and Technology, MOE Key Laboratory on Luminescence and Real-Time Analysis, Southwest University, Chongqing 400715, China

Molecules 2017, 22(5), 740; https://doi.org/10.3390/molecules22050740 - 4 May 2017

Cited by 8 | Viewed by 5797

Abstract

Molecular rotors with an off-center axis and the chiral feature of achiral CuPc molecules on a semi-metallic Bi(111) surface have been investigated by means of a scanning tunneling microscopy (STM) at liquid nitrogen (LN₂) temperature. The rotation axis of each CuPc [...] Read more.

Molecular rotors with an off-center axis and the chiral feature of achiral CuPc molecules on a semi-metallic Bi(111) surface have been investigated by means of a scanning tunneling microscopy (STM) at liquid nitrogen (LN₂) temperature. The rotation axis of each CuPc molecular rotor is located at the end of a phthalocyanine group. As molecular coverage increases, the CuPc molecules are self-assembled into various nanoclusters and finally into two-dimensional (2D) domains, in which each CuPc molecule exhibits an apparent chiral feature. Such chiral features of the CuPc molecules can be attributed to the combined effect of asymmetric charge transfer between the CuPc and Bi(111) substrate, and the intermolecular van der Waals interactions. Full article

(This article belongs to the Special Issue Porphyrins and Phthalocyanines: Synthesis, Properties and Applications)

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11 pages, 723 KiB

Open AccessArticle

A Cost-Efficient Method for Unsymmetrical Meso-Aryl Porphyrin Synthesis Using NaY Zeolite as an Inorganic Acid Catalyst

by Mário J. F. Calvete^*

, Lucas D. Dias

, César A. Henriques, Sara M. A. Pinto

, Rui M. B. Carrilho and Mariette M. Pereira^*

Coimbra Chemistry Centre, CQC, Departamento de Química, Faculdade de Ciências e Tecnologia da Universidade de Coimbra, Rua Larga, 3004-535 Coimbra, Portugal

Molecules 2017, 22(5), 741; https://doi.org/10.3390/molecules22050741 - 5 May 2017

Cited by 19 | Viewed by 6731

Abstract

Herein we report the synthesis of unsymmetrical meso-aryl substituted porphyrins, using NaY zeolite as an inorganic acid catalyst. A comparative study between this method and the several synthetic strategies available in the literature was carried out. Our method presented a better, more [...] Read more.

Herein we report the synthesis of unsymmetrical meso-aryl substituted porphyrins, using NaY zeolite as an inorganic acid catalyst. A comparative study between this method and the several synthetic strategies available in the literature was carried out. Our method presented a better, more cost-efficient rationale and displayed a significantly lower environmental impact. Furthermore, it was possible to verify the scalability of the process as well as the reutilization of the inorganic catalyst NaY (up to 6 times) without significant yield decrease. In addition, this method was applied to the synthesis of several other unsymmetrical porphyrins, from a low melting point porphyrin to mono-carboxylated halogenated unsymmetrical porphyrins, in yields higher than those found in the literature. Additionally, for the first time, two acetamide functionalized halogenated porphyrins were prepared in high yields. This methodology opens the way to the preparation of high yielding functionalized porphyrins, which can be easily immobilized for a variety of applications, either in catalysis or in biomedicine. Full article

(This article belongs to the Special Issue Porphyrins and Phthalocyanines: Synthesis, Properties and Applications)

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14 pages, 2703 KiB

Open AccessArticle

AlCl₃·6H₂O-Catalyzed Friedel-Crafts Alkylation of Indoles by the para-Quinone Methide Moiety of Celastrol

by Yi Zhu^1,†, Ziwen Chen^1,†, Zhenfei Huang¹, Siwei Yan¹, Zhuoer Li¹, Hu Zhou¹, Xiaokun Zhang^1,2, Ying Su^1,2,* and Zhiping Zeng^1,*

¹ School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen 361102, China

² Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA

^† These authors contributed equally to this work.

Molecules 2017, 22(5), 742; https://doi.org/10.3390/molecules22050742 - 16 May 2017

Cited by 8 | Viewed by 9011

Abstract

A classical Friedel-Crafts alkylation of different indoles catalyzed by AlCl₃·6H₂O has been developed for a well-known important natural product, celastrol, resulting in a series of derivatives for further biological evaluation. The catalyst loading was reduced to 5 mol %, [...] Read more.

A classical Friedel-Crafts alkylation of different indoles catalyzed by AlCl₃·6H₂O has been developed for a well-known important natural product, celastrol, resulting in a series of derivatives for further biological evaluation. The catalyst loading was reduced to 5 mol %, the reaction proceeds at ambient temperature and reaction time is only 3 h. The product yields range from 20% to 99%. A reaction mechanism is also proposed, based on our experiment results. Full article

(This article belongs to the Special Issue Synthesis and Modification of Natural Product)

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17 pages, 4518 KiB

Open AccessArticle

Quercetin from Polygonum capitatum Protects against Gastric Inflammation and Apoptosis Associated with Helicobacter pylori Infection by Affecting the Levels of p38MAPK, BCL-2 and BAX

by Shu Zhang¹, Jian Huang^2,*, Xiaoqin Xie¹, Yun He¹, Fei Mo¹ and Zhaoxun Luo¹

¹ Department of Clinical Laboratory, School of Medical Laboratory Sciences, Guizhou Medical University, Guiyang 550004, China

² Department of Clinical Biochemistry, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China

Molecules 2017, 22(5), 744; https://doi.org/10.3390/molecules22050744 - 6 May 2017

Cited by 64 | Viewed by 7140

Abstract

Helicobacter pylori-associated gastritis is a major threat to public health and Polygonum capitatum (PC) may have beneficial effects on the disease. However, the molecular mechanism remains unknown. Quercetin was isolated from PC and found to be a main bioactive compound. The effects [...] Read more.

Helicobacter pylori-associated gastritis is a major threat to public health and Polygonum capitatum (PC) may have beneficial effects on the disease. However, the molecular mechanism remains unknown. Quercetin was isolated from PC and found to be a main bioactive compound. The effects of quercetin on human gastric cancer cells GES-1 were determined by xCELLigence. H. pylori-infected mouse models were established. All mice were divided into three groups: control (CG, healthy mice), model (MG, H. pylori infection) and quercetin (QG, mouse model treated by quercetin) groups. IL-8 (interleukin-8) levels were detected via enzyme-linked immunosorbent assay (ELISA). Cell cycle and apoptosis were measured by flow cytometry (FCM). Quantitative reverse transcription PCR (qRT-PCR) and Western Blot were used to detect the levels of p38MAPK (38-kD tyrosine phosphorylated protein kinase), apoptosis regulator BCL-2-associated protein X (BAX) and B cell lymphoma gene 2 (BCL-2). The levels of IL-8 were increased by 8.1-fold in a MG group and 4.3-fold in a QG group when compared with a CG group. In a MG group, G0–G1(phases of the cell cycle)% ratio was higher than a CG group while S phase fraction was lower in a model group than in a control group (p < 0.01). After quercetin treatment, G0–G1% ratio was lower in a QG group than a MG group while S phase fraction was higher than a MG group (p < 0.01). Quercetin treatment reduced the levels of p38MAPK and BAX, and increased the levels of BCL-2 when compared with a MG group (p < 0.05). Quercetin regulates the balance of gastric cell proliferation and apoptosis to protect against gastritis. Quercetin protects against gastric inflammation and apoptosis associated with H. pylori infection by affecting the levels of p38MAPK, BCL-2 and BAX. Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 1584 KiB

Open AccessArticle

Modulation of HO-1 by Ferulic Acid Attenuates Adipocyte Differentiation in 3T3-L1 Cells

by Eun-Jeong Koh^†, Kui-Jin Kim^†, Young-Jin Seo, Jia Choi and Boo-Yong Lee^*

¹ Department of Food Science and Biotechnology, College of Life Science, CHA University, Seongnam, Kyeonggi 13488, Korea

^† These authors equally contributed to this work.

Molecules 2017, 22(5), 745; https://doi.org/10.3390/molecules22050745 - 5 May 2017

Cited by 22 | Viewed by 6465

Abstract

Ferulic acid (FA) is phenolic compound found in fruits. Many studies have reported that FA has diverse therapeutic effects against metabolic diseases. However, the mechanism by which FA modulates adipogenesis via the expression of heme oxygenase-1 (HO-1) implicated in suppression of adipocyte differentiation [...] Read more.

Ferulic acid (FA) is phenolic compound found in fruits. Many studies have reported that FA has diverse therapeutic effects against metabolic diseases. However, the mechanism by which FA modulates adipogenesis via the expression of heme oxygenase-1 (HO-1) implicated in suppression of adipocyte differentiation is not fully understood. We investigated whether HO-1 can be activated by FA and suppress adipogenic factors in 3T3-L1. Our results showed that FA suppresses triglyceride-synthesizing enzymes, fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC). We observed that the expression of CCAAT/enhancer binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ) were suppressed by FA. In addition, HO-1 inhibitor stimulated lipid accumulation, while FA attenuated lipid accumulation in 3T3-L1 treated with HO-1 inhibitor. We also observed that the expression of HO-1 had the same tendency as C/EBP homologous protein 10 (CHOP10) during the mitotic clonal expansion (MCE) of adipogenesis. We next employed siRNA against HO-1 to clarify whether HO-1 regulates CHOP10. The results indicated that CHOP10 is downstream of HO-1. Furthermore, FA-mediated HO-1/CHOP10 axis activation prevented the initiation of MCE. Therefore, we demonstrated that FA is a positive regulator of HO-1 in 3T3-L1, and may be an effective bioactive compound to reduce adipocyte tissue mass. Full article

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

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13 pages, 5223 KiB

Open AccessArticle

Roles of Glycoproteins in the Diagnosis and Differential Diagnosis of Chronic and Latent Keshan Disease

by Sen Wang^1,†, Zheng Fan^2,†, Bing Zhou³, Yingting Wang¹, Peiru Du¹, Wuhong Tan^1,*, Mikko J. Lammi^1,4,* and Xiong Guo¹

¹ School of Public Health, Health Science Center of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China

² Office of Teaching Affairs, Xi’an University, Xi’an 710061, Shaanxi, China

³ Key Laboratory of Hormones and Development (Ministry of Health), Key laboratory of metabolic disease (Tianjin), Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China

⁴ Department of Integrative Medical Biology, University of Umeå, Umeå 90187, Sweden

^† These authors contributed equally to this work.

Molecules 2017, 22(5), 746; https://doi.org/10.3390/molecules22050746 - 8 May 2017

Cited by 8 | Viewed by 5318

Abstract

We aimed to explore the roles of glycoproteins in the pathogenesis of chronic and latent Keshan disease (CKD and LKD), and screen the lectins as indicators of significant differences in glycoproteins of KD saliva and serum. Blood and saliva were collected from 50 [...] Read more.

We aimed to explore the roles of glycoproteins in the pathogenesis of chronic and latent Keshan disease (CKD and LKD), and screen the lectins as indicators of significant differences in glycoproteins of KD saliva and serum. Blood and saliva were collected from 50 CKD, 50 LKD patients and 54 normal individuals. Saliva and serum lectin microarrays and saliva and serum microarrays were used to screen and verify the differences in the levels of lectin among the three groups. In the male saliva lectin microarray, Solanum tuberosum (potato) lectin (STL) and other 9 lectins showed differences between CKD and normal; STL and other 9 lectins showed differences between LKD and normal; Aleuria aurantia lectin (AAL) and other 15 lectins showed differences between CKD and LKD. In the female saliva microarray, Griffonia (Bandeiraea) simplicifolia lectin I (GSL-I) and other 9 lectins showed differences between CKD and normal; STL and other 7 lectins showed differences between LKD and normal; Maackia amurensis lectin I (MAL-I) and Triticum vulgaris (WGA) showed difference between CKD and LKD. In the male serum lectin microarray, Psophocarpus tetragonolobus lectin I (PTL-I) and other 16 lectins showed differences between CKD and normal; Ulexeuropaeus agglutinin I (UEA-I) and other 9 lectins showed differences between LKD and normal; AAL and other 13 lectins showed differences between CKD and LKD. In the female serum lectin microarray, WGA and other 13 lectins showed differences between CKD and normal; Euonymus europaeus lectin (EEL) and other 6 lectins showed differences between LKD and normal; MAL-I and other 14 lectins showed differences between CKD and LKD. Carbohydrate chain GlcNAc and α-Gal may play crucial roles in the pathogenesis of KD. STL may be considered the diagnostic biomarker for male CKD and LKD, while WGA may be useful in distinguishing between the two stages. STL may be considered the diagnostic biomarker for female LKD. Full article

(This article belongs to the Special Issue Synthesis and Biological Applications of Glycoconjugates)

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12 pages, 1589 KiB

Open AccessArticle

In Vitro Anticancer Activity and Structural Characterization of Ubiquinones from Antrodia cinnamomea Mycelium

by I-Chuan Yen^1,2, Shih-Yu Lee³

, Kuen-Tze Lin⁴, Feng-Yi Lai³, Mao-Tien Kuo⁵ and Wen-Liang Chang^2,*

¹ Graduate Institute of Medical Science, National Defense Medical Center, No.116, Sec.6, Minchuan East Road, Neihu District, Taipei 114, Taiwan

² School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan

³ Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei 114, Taiwan

⁴ Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan

⁵ LanTyng Biotech, Co, Ltd., Taipei 114, Taiwan

Molecules 2017, 22(5), 747; https://doi.org/10.3390/molecules22050747 - 6 May 2017

Cited by 12 | Viewed by 6308

Abstract

Two new ubiquinones, named antrocinnamone and 4-acetylantrocamol LT3, were isolated along with six known ubiquinones from Antrodia cinnamomea (Polyporaceae) mycelium. The developed HPLC analysis methods successfully identified eight different ubiquinones, two benzenoids, and one maleic acid derivative from A. cinnamomea. The ubiquinones [...] Read more.

Two new ubiquinones, named antrocinnamone and 4-acetylantrocamol LT3, were isolated along with six known ubiquinones from Antrodia cinnamomea (Polyporaceae) mycelium. The developed HPLC analysis methods successfully identified eight different ubiquinones, two benzenoids, and one maleic acid derivative from A. cinnamomea. The ubiquinones 1–8 exhibited potential and selective cytotoxic activity against three human cancer cell lines, with IC₅₀ values ranging from 0.001 to 35.883 μM. We suggest that the different cytotoxicity levels were related to their chemical structures, especially the 4-hydroxycyclohex-2-enone ring and the presence of a free hydroxyl group in the side chain. The suppression by 4-acetylantrocamol LT3 stopped the cell cycle at the beginning of the G2-M phase thus making the cell cycle arrest at the sub-G1 phase as compared with control cells. Full article

(This article belongs to the Special Issue New Methodologies in Natural Product Analytics and Structure Elucidation)

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19 pages, 828 KiB

Open AccessArticle

Anti-Onchocerca and Anti-Caenorhabditis Activity of a Hydro-Alcoholic Extract from the Fruits of Acacia nilotica and Some Proanthocyanidin Derivatives

by Jacqueline Dikti Vildina¹, Justin Kalmobe¹, Boursou Djafsia¹, Thomas J. Schmidt²

, Eva Liebau³ and Dieudonne Ndjonka^1,*

¹ Department of Biological Sciences, Faculty of Science, University of Ngaoundere, P.O. Box 454, Ngaoundere, Cameroon

² Institute of Pharmaceutical Biology and Phytochemistry (IPBP), University of Münster, PharmaCampus Correnstrasse 48, D-48149 Münster, Germany

³ Institute for Zoophysiology, University of Münster, Schlossplatz 8, D-48143 Münster, Germany

Molecules 2017, 22(5), 748; https://doi.org/10.3390/molecules22050748 - 6 May 2017

Cited by 27 | Viewed by 6116

Abstract

Acacia nilotica fruits with high tannin content are used in the northern parts of Cameroon as anti-filarial remedies by traditional healers. In this study, the hydro-alcoholic fruit extract (crude extract (CE)) and, one of the main constituents in its most active fractions, (+)-catechin-3- [...] Read more.

Acacia nilotica fruits with high tannin content are used in the northern parts of Cameroon as anti-filarial remedies by traditional healers. In this study, the hydro-alcoholic fruit extract (crude extract (CE)) and, one of the main constituents in its most active fractions, (+)-catechin-3-O-gallate (CG), as well as four related proanthocyanidins, (−)-epicatechin-3-O-gallate (ECG), (+)-gallocatechin (GC), (−)-epigallocatechin (EGC) and (−)-epigallocatechin-3-O-gallate (EGCG), were assessed for their potential in vitro anthelmintic properties against the free-living model organism Caenorhabditis elegans and against the cattle filarial parasite Onchocerca ochengi. Worms were incubated in the presence of different concentrations of fruit extract, fractions and pure compounds. The effects on mortality were monitored after 48 h. The plant extract and all of the pure tested compounds were active against O. ochengi (LC₅₀ ranging from 1.2 to 11.5 µg/mL on males) and C. elegans (LC₅₀ ranging from 33.8 to 350 µg/mL on wild type). While high LC₅₀ were required for the effects of the compounds on C. elegans, very low LC₅₀ were required against O. ochengi. Importantly, tests for acute oral toxicity (lowest dose: 10 mg/kg) in Wistar rats demonstrated that crude extract and pure compounds were non-toxic and safe to use. Additionally, the results of cytotoxicity tests with the Caco-2 cell line (CC₅₀ ranging from 47.1 to 93.2 µg/mL) confirmed the absence of significant toxicity of the crude extract and pure compounds. These results are in good accordance with the use of A. nilotica against nematode infections by traditional healers, herdsmen and pastoralists in Cameroon. Full article

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

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20 pages, 5112 KiB

Open AccessArticle

A Molecular Electron Density Theory Study of the Reactivity of Azomethine Imine in [3+2] Cycloaddition Reactions

by Luis R. Domingo^*

and Mar Ríos-Gutiérrez

Department of Organic Chemistry, University of Valencia, Dr. Moliner 50, E-46100 Burjassot, Valencia, Spain

Molecules 2017, 22(5), 750; https://doi.org/10.3390/molecules22050750 - 6 May 2017

Cited by 101 | Viewed by 7944

Abstract

The electronic structure and the participation of the simplest azomethine imine (AI) in [3+2] cycloaddition (32CA) reactions have been analysed within the Molecular Electron Density Theory (MEDT) using Density Functional Theory (DFT) calculations at the MPWB1K/6-311G(d) level. Topological analysis of the electron localisation [...] Read more.

The electronic structure and the participation of the simplest azomethine imine (AI) in [3+2] cycloaddition (32CA) reactions have been analysed within the Molecular Electron Density Theory (MEDT) using Density Functional Theory (DFT) calculations at the MPWB1K/6-311G(d) level. Topological analysis of the electron localisation function reveals that AI has a pseudoradical structure, while the conceptual DFT reactivity indices characterises this three-atom-component (TAC) as a moderate electrophile and a good nucleophile. The non-polar 32CA reaction of AI with ethylene takes place through a one-step mechanism with moderate activation energy, 8.7 kcal·mol⁻¹. A bonding evolution theory study indicates that this reaction takes place through a non-concerted [2n + 2τ] mechanism in which the C–C bond formation is clearly anticipated prior to the C–N one. On the other hand, the polar 32CA reaction of AI with dicyanoethylene takes place through a two-stage one-step mechanism. Now, the activation energy is only 0.4 kcal·mol⁻¹, in complete agreement with the high polar character of the more favourable regioisomeric transition state structure. The current MEDT study makes it possible to extend Domingo’s classification of 32CA reactions to a new pseudo(mono)radical type (pmr-type) of reactivity. Full article

(This article belongs to the Special Issue The Molecular Electron Density Theory: A Modern View of Molecular Reactivity in Organic Chemistry)

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12 pages, 9194 KiB

Open AccessArticle

Constrained Geometry Organotitanium Catalysts Supported on Nanosized Silica for Ethylene (co)Polymerization

by Kuo-Tseng Li^* and Ling-Huey Wu

Department of Chemical Engineering, Tunghai University, Taichung 407, Taiwan

Molecules 2017, 22(5), 751; https://doi.org/10.3390/molecules22050751 - 5 May 2017

Cited by 7 | Viewed by 5119

Abstract

Supported olefin polymerization catalysts can prevent reactor-fouling problems and produce uniform polymer particles. Constrained geometry complexes (CGCs) have less sterically hindered active sites than bis-cyclopentadienyl metallocene catalysts. In the literature, micrometer-sized silica particles were used for supporting CGC catalysts, which might have strong [...] Read more.

Supported olefin polymerization catalysts can prevent reactor-fouling problems and produce uniform polymer particles. Constrained geometry complexes (CGCs) have less sterically hindered active sites than bis-cyclopentadienyl metallocene catalysts. In the literature, micrometer-sized silica particles were used for supporting CGC catalysts, which might have strong mass transfer limitations. This study aims to improve the activity of supported CGC catalysts by using nanometer-sized silica. Ti[(C₅Me₄)SiMe₂(N^tBu)]Cl₂, a “constrained-geometry” titanium catalyst, was supported on MAO-treated silicas (nano-sized and micro-sized) by an impregnation method. Ethylene homo-polymerization and co-polymerization with 1-octene were carried out in a temperature range of 80–120 °C using toluene as the solvent. Catalysts prepared and polymers produced were characterized. For both catalysts and for both reactions, the maximum activities occurred at 100 °C, which is significantly higher than that (60 °C) reported before for supported bis-cyclopentadienyl metallocene catalysts containing zirconium, and is lower than that (≥140 °C) used for unsupported Ti[(C₅Me₄)SiMe₂(N^tBu)]Me₂ catalyst. Activities of nano-sized catalyst were 2.6 and 1.6 times those of micro-sized catalyst for homopolymerization and copolymerization, respectively. The former produced polymers with higher crystallinity and melting point than the latter. In addition, copolymer produced with nanosized catalyst contained more 1-octene than that produced with microsized catalyst. Full article

(This article belongs to the Special Issue Organometallic Catalysis for Olefin Polymerization/Oligomerization)

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7 pages, 2671 KiB

Open AccessArticle

Synthesis of Europium-Doped Fluorapatite Nanorods and Their Biomedical Applications in Drug Delivery

by Haifeng Zeng¹, Xiyu Li², Muyang Sun³, Sufan Wu^1,* and Haifeng Chen^3,*

¹ Department of Plastic Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China

² State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China

³ Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China

Molecules 2017, 22(5), 753; https://doi.org/10.3390/molecules22050753 - 6 May 2017

Cited by 27 | Viewed by 6958

Abstract

Europium (Eu)-doped fluorapatite (FA) nanorods have a biocompatibility similar to that of hydroxyapatite (HA) for use as cell imaging biomaterials due to their luminescent property. Here, we discuss the new application of europium-doped fluorapatite (Eu-FA) nanorods as an anticancer drug carrier. The Eu-FA [...] Read more.

Europium (Eu)-doped fluorapatite (FA) nanorods have a biocompatibility similar to that of hydroxyapatite (HA) for use as cell imaging biomaterials due to their luminescent property. Here, we discuss the new application of europium-doped fluorapatite (Eu-FA) nanorods as an anticancer drug carrier. The Eu-FA nanorods were prepared by using a hydrothermal method. The morphology, crystal structure, fluorescence, and composition were investigated. The specific crystal structure enables the effective loading of drug molecules. Doxorubicin (DOX), which was used as a model anticancer drug, effectively loaded onto the surface of the nanorods. The DOX release was pH-dependent and occurred more rapidly at pH 5.5 than at pH 7.4. The intracellular penetration of the DOX-loaded Eu-FA nanorods (Eu-FA/DOX) can be imaged in situ due to the self-fluorescence property. Treatment of melanoma A375 cells with Eu-FA/DOX elicited a more effective apoptosis rate than direct DOX treatment. Overall, Eu-FA exhibits potential for tracking and treating tumors and may be potentially useful as a multifunctional carrier system to effectively load and sustainably deliver drugs. Full article

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

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13 pages, 18221 KiB

Open AccessArticle

Protective Effects of Amarogentin against Carbon Tetrachloride-Induced Liver Fibrosis in Mice

by Ya Zhang¹, Hang Zhao¹, Hua Li¹, Wei Cao¹, Fang Wang¹, Tian Zhang² and Si-Wang Wang^1,*

¹ Department of Natural Medicine, School of Pharmacy, Fourth Military Medical University, 169 West Changle Road, Xi’an 710032, China

² Xi’an Day Natural Inc., F501 Gazelle Valley, Pioneering R&D Park, 69 Jinye Road, Xi’an 710077, China

Molecules 2017, 22(5), 754; https://doi.org/10.3390/molecules22050754 - 6 May 2017

Cited by 27 | Viewed by 6018

Abstract

Amarogentin, a secoiridoid glycoside that is mainly extracted from Swertia and Gentiana roots, has been suggested to exhibit many biological effects, including anti-oxidative, anti-tumour, and anti-diabetic activities. The present study was designed to evaluate the protective effects of amarogentin on carbon tetrachloride-induced liver [...] Read more.

Amarogentin, a secoiridoid glycoside that is mainly extracted from Swertia and Gentiana roots, has been suggested to exhibit many biological effects, including anti-oxidative, anti-tumour, and anti-diabetic activities. The present study was designed to evaluate the protective effects of amarogentin on carbon tetrachloride-induced liver fibrosis in vivo and the underlying mechanism. Fibrosis was induced by subcutaneous injections of 6 mL/kg of 20% carbon tetrachloride (dissolved in olive oil) twice per week for seven weeks. Mice were orally treated with 25, 50, and 100 mg/kg amarogentin and with colchicine as a positive control. Biochemical assays and histopathological investigations showed that amarogentin delayed the formation of liver fibrosis; decreased alanine aminotransferase, aspartate aminotransferase, malondialdehyde and hydroxyproline levels; and increased albumin, cyclic guanosine monophosphate, glutathione peroxidase, and superoxide dismutase levels. Moreover, amarogentin exhibited downregulation of α-smooth muscle actin and transforming growth factor-β₁ levels in immunohistochemical and Western blot analyses. The levels of phosphorylated extracellular regulated protein kinases, c-Jun N-terminal kinase, and p38 were also significantly reduced in all amarogentin-treated groups in a dose-dependent manner. These findings demonstrated that amarogentin exerted significant hepatoprotective effects against carbon tetrachloride-induced liver fibrosis in mice and suggested that the effect of amarogentin against liver fibrosis may be by anti-oxidative properties and suppressing the mitogen-activated protein kinase signalling pathway. Full article

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13 pages, 3317 KiB

Open AccessArticle

Isotactic and Syndiotactic Alternating Ethylene/Propylene Copolymers Obtained Through Non-Catalytic Hydrogenation of Highly Stereoregular cis-1,4 Poly(1,3-diene)s

by Giovanni Ricci^1,*

, Antonella Caterina Boccia¹

, Giuseppe Leone¹

, Ivana Pierro^1,2, Giorgia Zanchin^1,3, Miriam Scoti², Finizia Auriemma²

and Claudio De Rosa²

¹ CNR-Istituto per lo Studio delle Macromolecole (ISMAC), Via A. Corti 12, I-20133 Milano, Italy

² Dipartimento di Scienze Chimiche, Università di Napoli Federico II, Complesso Monte S. Angelo, Via Cintia, I-80126 Napoli, Italy

³ Dipartimento di Chimica, Università degli Studi di Milano, via C. Golgi 19, I-20133 Milano, Italy

Molecules 2017, 22(5), 755; https://doi.org/10.3390/molecules22050755 - 6 May 2017

Cited by 12 | Viewed by 6298

Abstract

The homogeneous non-catalytic hydrogenation of cis-1,4 poly(isoprene), isotactic cis-1,4 poly(1,3-pentadiene) and syndiotactic cis-1,4 poly(1,3-pentadiene) with diimide, formed by thermal decomposition of para-toluenesulfonylhydrazide, is examined. Perfectly alternating ethylene/propylene copolymers having different tacticity (i.e., isotactic and syndiotactic), which are difficult to [...] Read more.

The homogeneous non-catalytic hydrogenation of cis-1,4 poly(isoprene), isotactic cis-1,4 poly(1,3-pentadiene) and syndiotactic cis-1,4 poly(1,3-pentadiene) with diimide, formed by thermal decomposition of para-toluenesulfonylhydrazide, is examined. Perfectly alternating ethylene/propylene copolymers having different tacticity (i.e., isotactic and syndiotactic), which are difficult to synthesize by stereospecific copolymerization of the corresponding monomers, are obtained. Both isotactic and syndiotactic alternating ethylene/propylene copolymers are amorphous, with very low glass transition temperatures. Full article

(This article belongs to the Special Issue Organometallic Catalysis for Olefin Polymerization/Oligomerization)

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14 pages, 6942 KiB

Open AccessArticle

Hepatoprotective Effect of Carboxymethyl Pachyman in Fluorouracil-Treated CT26-Bearing Mice

by Canhong Wang^1,2,†, Xiaowei Huo^1,†, Li Gao¹, Guibo Sun¹ and Cao Li^1,*

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

² Hainan Branch Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Haikou 570311, China

^† These authors contribute equally to this work.

Molecules 2017, 22(5), 756; https://doi.org/10.3390/molecules22050756 - 6 May 2017

Cited by 24 | Viewed by 5539

Abstract

5-Fluorouracil (5-FU) is the chemotherapeutic agent of first choice for the treatment ofcolorectal cancer, however, treatment-related liver toxicity remains a major concern. Thereby, it is desirable to search for novel therapeutic approaches that can effectively enhance curative effects and reduce the toxic side [...] Read more.

5-Fluorouracil (5-FU) is the chemotherapeutic agent of first choice for the treatment ofcolorectal cancer, however, treatment-related liver toxicity remains a major concern. Thereby, it is desirable to search for novel therapeutic approaches that can effectively enhance curative effects and reduce the toxic side effects of 5-FU. Carboxymethyl Pachyman (CMP) exhibits strong antitumor properties, but the antitumor and hepatoprotective effects of CMP and the molecular mechanisms behind these activities, are however poorly explored. Thereby, the purpose of the present study was to evaluate the hepatoprotective effect of CMP in 5-FU-treated CT26-bearing mice, and further explore the underlying mechanism(s) of action. Initially, a CT26 colon carcinoma xenograft mice model was established. The immune organ indexes, blood indicators, liver tissue injury, and indicators associated with inflammation, antioxidant and apoptosis were then measured. Our results showed that CMP administration increased the tumor inhibitory rates of 5-FU and, meanwhile, it reversed reduction of peripheral white blood cells (WBC) and bone marrow nucleated cells (BMNC), increase of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and decrease of superoxide dismutase (SOD), catalase (CAT), GSH-Px and glutathione(GSH) induced by 5-FU. Moreover, CMP in combination with 5-FU alleviated severe liver injury induced by 5-FU via reducing the levels of ROS, IL-1β, and IL-6, decreasing expression of p-IκB-α, NF-κB, p-NF-κB, pp38 and Bax, and elevating levels of Nrf2, GCL, HO-1 and Bcl-2. Collectively, these outcomes suggested that CMP effectively enhanced the curative effects of 5-FU and simultaneously reduced the liver injuries induced by 5-FU in CT26-bearing mice, and the mechanism may be associated with regulation of NF-κB, Nrf2-ARE and MAPK/P38/JNK pathways. Full article

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12 pages, 930 KiB

Open AccessArticle

Synthesis and Biological Evaluation of New Substituted Hantzsch Thiazole Derivatives from Environmentally Benign One-Pot Synthesis Using Silica Supported Tungstosilisic Acid as Reusable Catalyst

by Houria Bouherrou¹, Aicha Saidoun¹, Ahmed Abderrahmani², Lamia Abdellaziz², Yahia Rachedi^1,*, Françoise Dumas³ and Albert Demenceau⁴

¹ Laboratory of Applied Organic Chemistry, Faculty of Chemistry, University of Science and Technology Houari Boumediene, BP 32, El Alia, 16111 Bab Ezzouar, Algiers, Algeria

² Laboratory of Cellular and Molecular Biology, Faculty of Biological Sciences, USTHB, BP 32, El Alia, 16111 Bab Ezzouar, Algiers, Algeria

³ Laboratoire BioCIS, UMR CNRS8076, Chimie des Substances Naturelles, IPSIT and LabEx LERMIT, CNRS, Université Paris-Saclay, Université Paris-Sud, Faculté de Pharmacie, 5, rue Jean-Baptiste Clément, 92296 Châtenay-Malabry CEDEX, France

⁴ Laboratoire de chimie macromoléculaire et catalyse organique, Institut de Chimie (B6a), Université de Liège, Quartier Agora, Allée du 6 Août, 4000 Liège (Sart-Tilman), Belgique

Molecules 2017, 22(5), 757; https://doi.org/10.3390/molecules22050757 - 7 May 2017

Cited by 30 | Viewed by 8810

Abstract

An efficient and green method has been developed for the synthesis of new substituted Hantzsch thiazole derivatives in 79%–90% yield, via the one-pot multi-component procedure, by the reaction of 3-(bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one, thiourea and substituted benzaldehydes in the presence of silica supported tungstosilisic [...] Read more.

An efficient and green method has been developed for the synthesis of new substituted Hantzsch thiazole derivatives in 79%–90% yield, via the one-pot multi-component procedure, by the reaction of 3-(bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one, thiourea and substituted benzaldehydes in the presence of silica supported tungstosilisic acid, as a reusable catalyst, under conventional heating or under ultrasonic irradiation. The catalyst is recoverable by a simple filtration and can be reused in the subsequent reactions. Most of the thiazoles exhibited significant antibacterial activity compared toamoxicillin and ciprofloxacin as positive controls. In addition, the new compounds showed moderate to good antioxidant (DPPH) radical scavenging activity. Full article

(This article belongs to the Special Issue Multicomponent Reaction-Based Synthesis of Bioactive Molecules)

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11 pages, 1551 KiB

Open AccessArticle

Tuning the Geometrical Structures and Optical Properties of Blue-Emitting Iridium(III) Complexes through Dimethylamine Substitutions: A Theoretical Study

by Xue-Feng Ren^1,2, Hong-Qu Tang¹ and Guo-Jun Kang^1,*

¹ Low Carbon Energy Institute, School of Chemical Engineering & Technology, China University of Mining &Technology, Xuzhou 221008, China

² Fukui Institute for Fundamental Chemistry, Kyoto University, 34-4 Takano Nishihiraki-cho, Sakyo, Kyoto 606-8103, Japan

Molecules 2017, 22(5), 758; https://doi.org/10.3390/molecules22050758 - 7 May 2017

Cited by 5 | Viewed by 4313

Abstract

The geometrical structures and photophysical properties of Ir(4,6-dFppy)₂(pic) (FIrpic) and its derivative (o-FIr, m-FIr, p-FIr) with dimethylamine substituted at the picolinic acid (N^∧O) ligand were fully investigated by density functional theory and time-dependent density functional [...] Read more.

The geometrical structures and photophysical properties of Ir(4,6-dFppy)₂(pic) (FIrpic) and its derivative (o-FIr, m-FIr, p-FIr) with dimethylamine substituted at the picolinic acid (N^∧O) ligand were fully investigated by density functional theory and time-dependent density functional theory. The simulated electronic structure, as well as absorption and emission spectra of FIrpic are in good agreement with the experimental observations. The introduction of dimethylamine at the N^∧O ligand at different positions is beneficial to extend the π-electron delocalization, increase HOMO energy levels, and hence improve the hole injection and transfer ability compared with those of FIrpic. Furthermore, o-FIr, m-FIr, and p-FIr have large absorption intensity and participation of metal-to-ligand charge transfer (MLCT) contribution in the main absorption spectra, which would be useful to improve the intersystem crossing (ISC) from the singlet to triplet excited state. More importantly, the high quantum yield of o-FIr (which is explained based on the detailed analysis of triplet energy, E_T1), participation of ³MLCT contribution in the phosphorescent spectra, and energy difference between ³MLCT and triplet metal centered (³MC) d-d excited state compared with m-FIr and p-FIr indicate that o-FIr is expected to be an excellent blue phosphorescence emitter with high efficiency. Full article

(This article belongs to the Special Issue Organic Light Emitting Diodes)

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11 pages, 1495 KiB

Open AccessArticle

The Functional Characterization of a Site-Specific Apigenin 4′-O-methyltransferase Synthesized by the Liverwort Species Plagiochasma appendiculatum

by Hui Liu

, Rui-Xue Xu, Shuai Gao and Ai-Xia Cheng^*

Key Laboratory of Chemical Biology of Natural Products, Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China

Molecules 2017, 22(5), 759; https://doi.org/10.3390/molecules22050759 - 7 May 2017

Cited by 31 | Viewed by 6932

Abstract

Apigenin, a widely distributed flavone, exhibits excellent antioxidant, anti-inflammatory, and antitumor properties. In addition, the methylation of apigenin is generally considered to result in better absorption and greatly increased bioavailability. Here, four putative Class II methyltransferase genes were identified from the transcriptome sequences [...] Read more.

Apigenin, a widely distributed flavone, exhibits excellent antioxidant, anti-inflammatory, and antitumor properties. In addition, the methylation of apigenin is generally considered to result in better absorption and greatly increased bioavailability. Here, four putative Class II methyltransferase genes were identified from the transcriptome sequences generated from the liverwort species Plagiochasma appendiculatum. Each was heterologously expressed as a His-fusion protein in Escherichia coli and their methylation activity against apigenin was tested. One of the four Class II OMT enzymes named 4′-O-methyltransferase (Pa4′OMT) was shown to react effectively with apigenin, catalyzing its conversion to acacetin. Besides the favorite substrate apigenin, the recombinant PaF4′OMT was shown to catalyze luteolin, naringenin, kaempferol, quercetin, genistein, scutellarein, and genkwanin to the corresponding 4′-methylation products. In vivo feeding experiments indicated that PaF4′OMT could convert apigenin to acacetin efficiently in E. coli and approximately 88.8 µM (25.2 mg/L) of product was synthesized when 100 µM of apigenin was supplemented. This is the first time that a Class II plant O-methyltransferase has been characterized in liverworts. Full article

(This article belongs to the Special Issue Synthesis and Modification of Natural Product)

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13 pages, 1634 KiB

Open AccessArticle

Synthesis of Aminoglycoside-2′-O-Methyl Oligoribonucleotide Fusions

by Lotta Granqvist¹, Andrzej Kraszewski^2,3, Ville Tähtinen¹ and Pasi Virta^1,*

¹ Department of Chemistry, University of Turku, Vatselankatu 2, 20014 Turku, Finland

² Centre of New Technologies, University of Warsaw, Banacha 2c, 02 097 Warsaw, Poland

³ College of Inter-Faculty Individual Studies in Mathematics and Natural Sciences, University of Warsaw, Banacha 2c, 02 097 Warsaw, Poland

Molecules 2017, 22(5), 760; https://doi.org/10.3390/molecules22050760 - 8 May 2017

Cited by 3 | Viewed by 5853

Abstract

Phosphoramidite building blocks of ribostamycin (3 and 4), that may be incorporated at any position of the oligonucleotide sequence, were synthesized. The building blocks, together with a previously described neomycin-modified solid support, were applied for the preparation of aminoglycoside-2′-O-methyl [...] Read more.

Phosphoramidite building blocks of ribostamycin (3 and 4), that may be incorporated at any position of the oligonucleotide sequence, were synthesized. The building blocks, together with a previously described neomycin-modified solid support, were applied for the preparation of aminoglycoside-2′-O-methyl oligoribonucleotide fusions. The fusions were used to clamp a single strand DNA sequence (a purine-rich strand of c-Myc promoter 1) to form triple helical 2′-O-methyl RNA/DNA-hybrid constructs. The potential of the aminoglycoside moieties to stabilize the triple helical constructs were studied by UV-melting profile analysis. Full article

(This article belongs to the Special Issue Synthesis and Applications of Oligonucleotide Conjugates)

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18 pages, 2719 KiB

Open AccessArticle

Phytochemical Profiles and Antimicrobial Activities of Allium cepa Red cv. and A. sativum Subjected to Different Drying Methods: A Comparative MS-Based Metabolomics

by Mohamed A. Farag^1,*, Sara E. Ali², Rashad H. Hodaya³, Hesham R. El-Seedi^4,5, Haider N. Sultani⁶, Annegret Laub⁶, Tarek F. Eissa⁷, Fouad O. F. Abou-Zaid³ and Ludger A. Wessjohann^6,*

¹ Pharmacognosy department, College of Pharmacy, Cairo University, Kasr el Aini St., P.B. 11562 Cairo, Egypt

² Department of Pharmaceutical Biology, Faculty of Pharmacy & Biotechnology, The German University in Cairo, P.B. 11835 Cairo, Egypt

³ Plant production Department, Desert Research Center, P.B. 11714 Cairo, Egypt

⁴ Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Box 574, SE-75 123 Uppsala, Sweden

⁵ Department of Chemistry, Faculty of Science, El-Menoufia University, 32512 Shebin El-Kom, Egypt

⁶ Leibniz Institute of Plant Biochemistry, Dept. Bioorganic Chemistry, Weinberg 3, D-06120 Halle (Saale), Germany

⁷ Pharmacognosy Department, College of Pharmacy, Modern Science and Arts University, P.B. 12566, Cairo, Egypt

Molecules 2017, 22(5), 761; https://doi.org/10.3390/molecules22050761 - 8 May 2017

Cited by 101 | Viewed by 12011

Abstract

Plants of the Allium genus produce sulphur compounds that give them a characteristic (alliaceous) flavour and mediate for their medicinal use. In this study, the chemical composition and antimicrobial properties of Allium cepa red cv. and A. sativum in the context of three [...] Read more.

Plants of the Allium genus produce sulphur compounds that give them a characteristic (alliaceous) flavour and mediate for their medicinal use. In this study, the chemical composition and antimicrobial properties of Allium cepa red cv. and A. sativum in the context of three different drying processes were assessed using metabolomics. Bulbs were dried using either microwave, air drying, or freeze drying and further subjected to chemical analysis of their composition of volatile and non-volatile metabolites. Volatiles were collected using solid phase micro-extraction (SPME) coupled to gas chromatography–mass spectrometry (GC/MS) with 42 identified volatiles including 30 sulphur compounds, four nitriles, three aromatics, and three esters. Profiling of the polar non-volatile metabolites via ultra-performance liquid chromatography coupled to high resolution MS (UPLC/MS) annotated 51 metabolites including dipeptides, flavonoids, phenolic acids, and fatty acids. Major peaks in GC/MS or UPLC/MS contributing to the discrimination between A. sativum and A. cepa red cv. were assigned to sulphur compounds and flavonoids. Whereas sulphur conjugates amounted to the major forms in A. sativum, flavonoids predominated in the chemical composition of A. cepa red cv. With regard to drying impact on Allium metabolites, notable and clear separations among specimens were revealed using principal component analysis (PCA). The PCA scores plot of the UPLC/MS dataset showed closer metabolite composition of microwave dried specimens to freeze dried ones, and distant from air dried bulbs, observed in both A. cepa and A. sativum. Compared to GC/MS, the UPLC/MS derived PCA model was more consistent and better in assessing the impact of drying on Allium metabolism. A phthalate derivative was found exclusively in a commercial garlic preparation via GC/MS, of yet unknown origin. The freeze dried samples of both Allium species exhibited stronger antimicrobial activities compared to dried specimens with A. sativum being in general more active than A. cepa red cv. Full article

(This article belongs to the Special Issue The Chemistry of Alliums)

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8 pages, 8800 KiB

Open AccessArticle

Ionic Liquid as an Efficient Medium for the Synthesis of Quinoline Derivatives via α-Chymotrypsin-Catalyzed Friedländer Condensation

by Zhang-Gao Le^1,2, Meng Liang², Zhong-Sheng Chen², Sui-Hong Zhang² and Zong-Bo Xie^1,2,*

¹ Jiangxi 2011 Joint Center for the Innovative Mass Spectrometry and Instrumentation, East China University of Technology, Nanchang 330013, China

² School of Chemistry, Biology and Material Science, East China University of Technology, Nanchang 330013, China

Molecules 2017, 22(5), 762; https://doi.org/10.3390/molecules22050762 - 8 May 2017

Cited by 22 | Viewed by 5911

Abstract

An efficient, convenient, and eco-friendly biocatalytic approach was developed for the synthesis of quinoline derivatives via the α-chymotrypsin-catalyzed Friedländer reaction. Interestingly, α-chymotrypsin exhibited higher catalytic activity in an ionic liquid (IL) aqueous solution as compared to that observed in our previous relevant study, [...] Read more.

An efficient, convenient, and eco-friendly biocatalytic approach was developed for the synthesis of quinoline derivatives via the α-chymotrypsin-catalyzed Friedländer reaction. Interestingly, α-chymotrypsin exhibited higher catalytic activity in an ionic liquid (IL) aqueous solution as compared to that observed in our previous relevant study, which was conducted using an organic solvent, and a series of substrates gave similar excellent yields at lower reaction temperature and under reduced enzyme-loading conditions. Full article

(This article belongs to the Special Issue Ionic Liquids and Deep Eutectic Solvents for Synthesis, Materials and Energy)

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14 pages, 4145 KiB

Open AccessArticle

Synthesis and Evaluation of Essential Oil-Derived β-Methoxyacrylate Derivatives as High Potential Fungicides

by Haihuan Su, Wenda Wang, Longzhu Bao, Shuangshuang Wang and Xiufang Cao^*

College of Science, Huazhong Agricultural University, Wuhan 430070, China

Molecules 2017, 22(5), 763; https://doi.org/10.3390/molecules22050763 - 8 May 2017

Cited by 9 | Viewed by 6305

Abstract

Essential oils (EOs) are plant-derived aroma compounds with a wide range of biological activity, but their actions are slow, and they are typically unstable to light or heat, difficult to extract and so on. To find highly potential fungicides derived from natural EOs, [...] Read more.

Essential oils (EOs) are plant-derived aroma compounds with a wide range of biological activity, but their actions are slow, and they are typically unstable to light or heat, difficult to extract and so on. To find highly potential fungicides derived from natural EOs, a series of essential oil-based β-methoxyacrylate derivatives have been designed and synthesized. The target compounds have been screened for their potential fungicidal activity against eleven species of plant pathogen fungi, including Alternaria alternata, Phomopsis adianticola, Pestalotiopsis theae, Sclerotinia sclerotiorum, etc. Compared with intermediates I, the parent essential oils and azoxystrobin, almost all of essential oil-based β-methoxyacrylate derivatives exhibited significantly better fungicidal activity. Further investigation revealed that some compounds showed remarkable inhibitory activities against Pestalotiopsis theae, Phomopsis adianticola, Sclerotinia sclerotiorum and Magnapothe grisea at different concentrations in contrast to the commercial product azoxystrobin. Compound II-8 exhibited particularly significant fungicidal activity. Full article

(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)

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14 pages, 7823 KiB

Open AccessArticle

Inferring the Genetic Determinants of Fruit Colors in Tomato by Carotenoid Profiling

by Hee Ju Yoo^1,†, Woo Jung Park^2,†, Gyu-Myung Lee¹, Chang-Sik Oh³, Inhwa Yeam⁴, Dong-Chan Won⁵, Chang Kil Kim¹ and Je Min Lee^1,*

¹ Department of Horticultural Science, Kyungpook National University, Daegu 41566, Korea

² Department of Marine Food Science and Technology, Gangneung-Wonju National University, Gangneung, Gangwon 25457, Korea

³ Department of Horticultural Biotechnology, College of Life Science, Kyung Hee University, Yongin, Gyeonggi 17104, Korea

⁴ Department of Horticulture and Breeding, Andong National University, Andong, Gyeongbuk 36729, Korea

⁵ Breeding Institute, Nongwoo Bio Co., Ltd., Yeoju, Gyeonggi 12655, Korea

^† These authors contributed equally to this work.

Molecules 2017, 22(5), 764; https://doi.org/10.3390/molecules22050764 - 8 May 2017

Cited by 55 | Viewed by 9350

Abstract

Carotenoids are essential for plant and animal nutrition, and are important factors in the variation of pigmentation in fruits, leaves, and flowers. Tomato is a model crop for studying the biology and biotechnology of fleshy fruits, particularly for understanding carotenoid biosynthesis. In commercial [...] Read more.

Carotenoids are essential for plant and animal nutrition, and are important factors in the variation of pigmentation in fruits, leaves, and flowers. Tomato is a model crop for studying the biology and biotechnology of fleshy fruits, particularly for understanding carotenoid biosynthesis. In commercial tomato cultivars and germplasms, visual phenotyping of the colors of ripe fruits can be done easily. However, subsequent analysis of metabolic profiling is necessary for hypothesizing genetic factors prior to performing time-consuming genetic analysis. We used high performance liquid chromatography (HPLC), employing a C₃₀ reverse-phase column, to efficiently resolve nine carotenoids and isomers of several carotenoids in yellow, orange, and red colored ripe tomatoes. High content of lycopene was detected in red tomatoes. The orange tomatoes contained three dominant carotenoids, namely δ-carotene, β-carotene, and prolycopene. The yellow tomatoes showed low levels of carotenoids compared to red or orange tomatoes. Based on the HPLC profiles, genes responsible for overproducing δ-carotene and prolycopene were described as lycopene ε-cyclase and carotenoid isomerase, respectively. Subsequent genetic analysis using DNA markers for segregating population and germplasms were conducted to confirm the hypothesis. This study establishes the usefulness of metabolic profiling for inferring the genetic determinants of fruit color. Full article

(This article belongs to the Section Molecular Diversity)

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7 pages, 941 KiB

Open AccessCommunication

Two New Metabolites from the Endophytic Fungus Alternaria sp. A744 Derived from Morinda officinalis

by Ying Wang^1,2,†, Hong-Xin Liu^1,†, Yu-Chan Chen¹, Zhang-Hua Sun¹, Hao-Hua Li¹, Sai-Ni Li¹, Ming-Li Yan² and Wei-Min Zhang^1,*

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

² School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411100, China

^† These authors contributed equally to this work.

Molecules 2017, 22(5), 765; https://doi.org/10.3390/molecules22050765 - 8 May 2017

Cited by 33 | Viewed by 4763

Abstract

Two new compounds isobenzofuranone A (1) and indandione B (2), together with eleven known compounds (3–13) were isolated from liquid cultures of an endophytic fungus Alternaria sp., which was obtained from the medicinal plant Morinda [...] Read more.

Two new compounds isobenzofuranone A (1) and indandione B (2), together with eleven known compounds (3–13) were isolated from liquid cultures of an endophytic fungus Alternaria sp., which was obtained from the medicinal plant Morinda officinalis. Among them, the indandione (2) showed a rarely occurring indanone skeleton in natural products. Their structures were elucidated mainly on the basis of extensive spectroscopic data analysis. All of the compounds were evaluated with cytotoxic and α-glucosidase inhibitory activity assays. Compounds 11 and 12 showed significant inhibitory activities against four tumor cell lines; MCF-7, HepG-2, NCI-H460 and SF-268, with IC₅₀ values in the range of 1.91–9.67 μM, and compounds 4, 5, 9, 10, 12 and 13 showed excellent inhibitory activities against α-glucosidase with IC₅₀ values in the range of 12.05–166.13 μM. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 17805 KiB

Open AccessArticle

Impact of a Microbial Cocktail Used as a Starter Culture on Cocoa Fermentation and Chocolate Flavor

by Igor Magalhães da Veiga Moreira¹, Leonardo De Figueiredo Vilela², Maria Gabriela Da Cruz Pedroso Miguel², Cledir Santos^2,3,*

, Nelson Lima⁴

and Rosane Freitas Schwan²

¹ Post-Graduate Program in Food Science, Federal University of Lavras, Lavras 37.200-000, Minas Gerais, Brazil

² Post-Graduate Program in Agricultural Microbiology, Federal University of Lavras, Lavras 37.200-000, Minas Gerais, Brazil

³ Department of Chemical Sciences and Natural Resources, Centro de Excelencia en Investigación Biotecnológica Aplicada al Medio Ambiente (CIBAMA), Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco 4811-230, Chile

⁴ CEB-Centre of Biological Engineering, Micoteca da Universidade do Minho, University of Minho, 4710-057 Braga, Portugal

Molecules 2017, 22(5), 766; https://doi.org/10.3390/molecules22050766 - 9 May 2017

Cited by 58 | Viewed by 11312

Abstract

Chocolate production suffered a vast impact with the emergence of the “witches’ broom” disease in cocoa plants. To recover cocoa production, many disease-resistant hybrid plants have been developed. However, some different cocoa hybrids produce cocoa beans that generate chocolate with variable quality. Fermentation [...] Read more.

Chocolate production suffered a vast impact with the emergence of the “witches’ broom” disease in cocoa plants. To recover cocoa production, many disease-resistant hybrid plants have been developed. However, some different cocoa hybrids produce cocoa beans that generate chocolate with variable quality. Fermentation of cocoa beans is a microbiological process that can be applied for the production of chocolate flavor precursors, leading to overcoming the problem of variable chocolate quality. The aim of this work was to use a cocktail of microorganisms as a starter culture on the fermentation of the ripe cocoa pods from PH15 cocoa hybrid, and evaluate its influence on the microbial communities present on the fermentative process on the compounds involved during the fermentation, and to perform the chocolate sensorial characterization. According to the results obtained, different volatile compounds were identified in fermented beans and in the chocolate produced. Bitterness was the dominant taste found in non-inoculated chocolate, while chocolate made with inoculated beans showed bitter, sweet, and cocoa tastes. 2,3-Butanediol and 2,3-dimethylpyrazine were considered as volatile compounds making the difference on the flavor of both chocolates. Saccharomyces cerevisiae UFLA CCMA 0200, Lactobacillus plantarum CCMA 0238, and Acetobacter pasteurianus CCMA 0241 are proposed as starter cultures for cocoa fermentation. Full article

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

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9 pages, 1845 KiB

Open AccessArticle

An Efficient Method for the Preparative Isolation and Purification of Flavonoids from Leaves of Crataegus pinnatifida by HSCCC and Pre-HPLC

by Lei Wen¹, Yunliang Lin², Ruimin Lv², Huijiao Yan², Jinqian Yu², Hengqiang Zhao², Xiao Wang²

and Daijie Wang^2,*

¹ College of Pharmacy, Shandong University of Traditional Chinese Medicine, 4655 Daxue Road, Jinan 250355, China

² Shandong Key Laboratory of TCM Quality Control Technology, Shandong Analysis and Test Center, Shandong Academy of Sciences, 19 Keyuan Street, Jinan 250014, China

Molecules 2017, 22(5), 767; https://doi.org/10.3390/molecules22050767 - 9 May 2017

Cited by 44 | Viewed by 7176

Abstract

In this work, flavonoid fraction from the leaves of Crataegus pinnatifida was separated into its seven main constituents using a combination of HSCCC coupled with pre-HPLC. In the first step, the total flavonoid extract was subjected to HSCCC with a two-solvent system of [...] Read more.

In this work, flavonoid fraction from the leaves of Crataegus pinnatifida was separated into its seven main constituents using a combination of HSCCC coupled with pre-HPLC. In the first step, the total flavonoid extract was subjected to HSCCC with a two-solvent system of chloroform/methanol/water/n-butanol (4:3:2:1.5, v/v), yielding four pure compounds, namely (–)-epicatechin (1), quercetin-3-O-(2,6-di-α-l-rhamnopyranosyl)-β-d-galactopyranoside (2), 4′′-O-glucosylvitexin (3) and 2′′-O-rhamnosylvitexin (4) as well as a mixture of three further flavonoids. An extrusion mode was used to rapidly separate quercetin-3-O-(2,6-di-α-l-rhamnopyranosyl)-β-d-galactopyranoside with a big K_D-value. In the second step, the mixture that resulted from HSCCC was separated by pre-HPLC, resulting in three pure compounds including: vitexin (5), hyperoside (6) and isoquercitrin (7). The purities of the isolated compounds were established to be over 98%, as determined by HPLC. The structures of these seven flavonoids were elucidated by ESI-MS and NMR spectroscopic analyses. Full article

(This article belongs to the Special Issue New Methodologies in Natural Product Analytics and Structure Elucidation)

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11 pages, 1409 KiB

Open AccessArticle

A Fluorescent Probe for Glycosaminoglycans Applied to the Detection of Dermatan Sulfate by a Mix-and-Read Assay

by Melissa Rappold, Ulrich Warttinger and Roland Krämer^*

Inorganic Chemistry Institute, Heidelberg University, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany

Molecules 2017, 22(5), 768; https://doi.org/10.3390/molecules22050768 - 9 May 2017

Cited by 14 | Viewed by 8302

Abstract

Glycosaminoglycans are complex biomolecules of great biological and medical importance. The quantification of glycosaminoglycans, in particular in complex matrices, is challenging due to their inherent structural heterogeneity. Heparin Red, a polycationic, fluorescent perylene diimide derivative, has recently emerged as a commercial probe for [...] Read more.

Glycosaminoglycans are complex biomolecules of great biological and medical importance. The quantification of glycosaminoglycans, in particular in complex matrices, is challenging due to their inherent structural heterogeneity. Heparin Red, a polycationic, fluorescent perylene diimide derivative, has recently emerged as a commercial probe for the convenient detection of heparins by a mix-and-read fluorescence assay. The probe also detects glycosaminoglycans with a lower negative charge density than heparin, although with lower sensitivity. We describe here the synthesis and characterization of a structurally related molecular probe with a higher positive charge of +10 (vs. +8 of Heparin Red). The superior performance of this probe is exemplified by the quantification of low dermatan sulfate concentrations in an aqueous matrix (quantification limit 1 ng/mL) and the detection of dermatan sulfate in blood plasma in a clinically relevant concentration range. The potential applications of this probe include monitoring the blood levels of dermatan sulfate after administration as an antithrombotic drug in the absence of heparin and other glycosaminoglycans. Full article

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

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13 pages, 2074 KiB

Open AccessArticle

Cs₂CO₃-Initiated Trifluoro-Methylation of Chalcones and Ketones for Practical Synthesis of Trifluoromethylated Tertiary Silyl Ethers

by Cheng Dong, Xing-Feng Bai, Ji-Yuan Lv, Yu-Ming Cui, Jian Cao, Zhan-Jiang Zheng^* and Li-Wen Xu^*

Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry of Education, Hangzhou Normal University, Hangzhou 311121, China

Molecules 2017, 22(5), 769; https://doi.org/10.3390/molecules22050769 - 18 May 2017

Cited by 7 | Viewed by 8823

Abstract

It was found that 1,2-trifluoromethylation reactions of ketones, enones, and aldehydes were easily accomplished using the Prakash reagent in the presence of catalytic amounts of cesium carbonate, which represents an experimentally convenient, atom-economic process for this anionic trifluoromethylation of non-enolisable aldehydes and ketones. [...] Read more.

It was found that 1,2-trifluoromethylation reactions of ketones, enones, and aldehydes were easily accomplished using the Prakash reagent in the presence of catalytic amounts of cesium carbonate, which represents an experimentally convenient, atom-economic process for this anionic trifluoromethylation of non-enolisable aldehydes and ketones. Full article

(This article belongs to the Special Issue Progress in Silicon and Organosilicon Chemistry)

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13 pages, 2426 KiB

Open AccessArticle

An Optimized Facile Procedure to Synthesize and Purify Allicin

by Frank Albrecht^1,†, Roman Leontiev^1,2,†, Claus Jacob² and Alan J. Slusarenko^1,*

¹ Department of Plant Physiology, RWTH Aachen University, D-52056 Aachen, Germany

² Division of Bioorganic Chemistry, School of Pharmacy, Campus B2 1, University of Saarland, D-66123 Saarbruecken, Saarland, Germany

^† These authors contributed equally to this work.

Molecules 2017, 22(5), 770; https://doi.org/10.3390/molecules22050770 - 10 May 2017

Cited by 32 | Viewed by 9395

Abstract

Allicin is a reactive sulfur species (RSS) and defence substance from garlic (Allium sativum L.). The compound is a broad-spectrum antibiotic that is also effective against multiple drug resistant (MDR) strains. A detailed protocol for allicin synthesis based on diallyl-disulfide (DADS) oxidation [...] Read more.

Allicin is a reactive sulfur species (RSS) and defence substance from garlic (Allium sativum L.). The compound is a broad-spectrum antibiotic that is also effective against multiple drug resistant (MDR) strains. A detailed protocol for allicin synthesis based on diallyl-disulfide (DADS) oxidation by H₂O₂ using acetic acid as a catalyst was published in 2001 by Lawson and Wang. Here we report on improvements to this basic method, clarify the mechanism of the reaction and show that it is zero-order with respect to DADS and first-order with respect to the concentration of H₂O₂. The progress of allicin synthesis and the reaction mechanism were analyzsd by high-performance liquid chromatography (HPLC) and the identity and purity of the products was verified with LC-MS and ¹H-NMR. We were able to obtain allicin of high purity (>98%) and >91% yield, with standard equipment available in any reasonable biological laboratory. This protocol will enable researchers to prepare and work with easily and cheaply prepared allicin of high quality. Full article

(This article belongs to the Special Issue The Chemistry of Alliums)

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16 pages, 13706 KiB

Open AccessArticle

Comparative Analysis of the Major Chemical Constituents in Salvia miltiorrhiza Roots, Stems, Leaves and Flowers during Different Growth Periods by UPLC-TQ-MS/MS and HPLC-ELSD Methods

by Huiting Zeng^1,2, Shulan Su^1,*, Xiang Xiang¹, Xiuxiu Sha¹, Zhenhua Zhu¹, Yanyan Wang¹, Sheng Guo¹, Hui Yan¹, Dawei Qian¹ and Jinao Duan^1,*

¹ Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Key Laboratory of Chinese Medicinal Resources Recycling Utilization, State Administration of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China

² Department of Traditional Chinese Medicine, Jiangxi Province Academy of Traditional Chinese Medicine, Nanchang 330046, China

Molecules 2017, 22(5), 771; https://doi.org/10.3390/molecules22050771 - 10 May 2017

Cited by 68 | Viewed by 6935

Abstract

Salvia miltiorrhiza is a traditional Chinese herbal medicine containing multiple components that contribute to its notable bioactivities. This article investigated the distribution and dynamic changes of chemical constituents in various parts of S. miltiorrhiza from different growth periods. An ultra-high performance liquid chromatography-triple [...] Read more.

Salvia miltiorrhiza is a traditional Chinese herbal medicine containing multiple components that contribute to its notable bioactivities. This article investigated the distribution and dynamic changes of chemical constituents in various parts of S. miltiorrhiza from different growth periods. An ultra-high performance liquid chromatography-triple quadrupole mass spectrometer (UPLC-TQ-MS/MS) and high-performance liquid chromatography coupled with evaporative light scattering detector (HPLC-ELSD) methods were developed for accurate determination of 24 compounds (including phenolic acids, flavonoids, triterpenes, and saccharides) in S. miltiorrhiza. The established methods were validated with good linearity, precision, repeatability, stability, and recovery. Results indicated that there were category and quantity discrepancies in different parts of the plant, for the roots mainly contained salvianolic acids and tanshinones, and most of the saccharides are stachyose. In the aerial parts, salvianolic acids, flavonoids, and triterpenes, except the tanshinones, were detected, and the saccharides were mainly monosaccharides. Dynamic accumulation analysis suggested the proper harvest time for S. miltiorrhiza Bunge was the seedling stage in spring, and for the aerial parts was July to August. This study provided valuable information for the development and utilization value of the aerial parts of S. miltiorrhiza and was useful for determining the optimal harvest time of the plant. Full article

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14 pages, 16347 KiB

Open AccessArticle

Synthesis and Characterization of Nano-Conducting Copolymer Composites: Efficient Sorbents for Organic Pollutants

by Khadija M. Emran¹, Shimaa M. Ali^1,2,* and Aishah L. L. Al-Oufi¹

¹ Department of Chemistry, Faculty of Science, Taibah University, Madinah 30002, Saudi Arabia

² Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt

Molecules 2017, 22(5), 772; https://doi.org/10.3390/molecules22050772 - 10 May 2017

Cited by 16 | Viewed by 4500

Abstract

Nano-conducting copolymers of aniline (ANI) and pyrrole (Py) with silica of different starting monomer ratios are prepared by oxidative chemical polymerization. X-ray diffraction (XRD) data showed that polyaniline (PANI) is the predominant phase in copolymer composites with a higher starting ANI monomer ratio [...] Read more.

Nano-conducting copolymers of aniline (ANI) and pyrrole (Py) with silica of different starting monomer ratios are prepared by oxidative chemical polymerization. X-ray diffraction (XRD) data showed that polyaniline (PANI) is the predominant phase in copolymer composites with a higher starting ANI monomer ratio while polypyrrole (PPy) is the major phase for other prepared samples. Transmission and scanning electron microscope images ascertained XRD results where hexagonal-shaped particles are assigned to PANI/SiO₂ and poly(9ANI-co-1Py)/SiO₂ samples; the cauliflower morphology can be observed for PPy/SiO₂, poly(1ANI-co-9Py)/SiO₂, poly(1ANI-co-2Py)/SiO₂, and poly(1ANI-co-1Py)/SiO₂ samples. One-dimensional nano-fibers can be obtained by using a starting monomer ratio of 2ANI:1Py during synthesis. Thermal analysis showed that copolymerization increases the thermal stability as compared with PANI/SiO₂ and PPy/SiO₂ composites. All prepared samples were applied as sorbents for Congo red dye from aqueous solutions. It was found that the sorption capacity value was affected by the starting monomer ratio; poly(2ANI-co-1Py)/SiO₂ has the highest sorption capacity; the q_m value is 142.9 mg g⁻¹ due to its highly-stabilized nano-structure. Full article

(This article belongs to the Section Green Chemistry)

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11 pages, 4907 KiB

Open AccessArticle

Direct Analyses of Secondary Metabolites by Mass Spectrometry Imaging (MSI) from Sunflower (Helianthus annuus L.) Trichomes

by Denise Brentan Silva^1,2

, Anna-Katharina Aschenbrenner³, Norberto Peporine Lopes^2,*

and Otmar Spring^3,*

¹ Laboratório de Produtos Naturais e Espectrometria de Massas (LaPNEM), Universidade Federal de Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil

² Núcleo de Pesquisas em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto 14040-020, SP, Brazil

³ Institute of Botany, University of Hohenheim, Garbenstraße 30, Stuttgart 70593, Germany

Molecules 2017, 22(5), 774; https://doi.org/10.3390/molecules22050774 - 10 May 2017

Cited by 24 | Viewed by 8045

Abstract

Helianthus annuus (sunflower) displays non-glandular trichomes (NGT), capitate glandular trichomes (CGT), and linear glandular trichomes (LGT), which reveal different chemical compositions and locations in different plant tissues. With matrix-assisted laser desorption/ionization (MALDI) and laser desorption/ionization (LDI) mass spectrometry imaging (MSI) techniques, efficient methods [...] Read more.

Helianthus annuus (sunflower) displays non-glandular trichomes (NGT), capitate glandular trichomes (CGT), and linear glandular trichomes (LGT), which reveal different chemical compositions and locations in different plant tissues. With matrix-assisted laser desorption/ionization (MALDI) and laser desorption/ionization (LDI) mass spectrometry imaging (MSI) techniques, efficient methods were developed to analyze the tissue distribution of secondary metabolites (flavonoids and sesquiterpenes) and proteins inside of trichomes. Herein, we analyzed sesquiterpene lactones, present in CGT, from leaf transversal sections using the matrix 2,5-dihydroxybenzoic acid (DHB) and α-cyano-4-hydroxycinnamic acid (CHCA) (mixture 1:1) with sodium ions added to increase the ionization in positive ion mode. The results observed for sesquiterpenes and polymethoxylated flavones from LGT were similar. However, upon desiccation, LGT changed their shape in the ionization source, complicating analyses by MSI mainly after matrix application. An alternative method could be applied to LGT regions by employing LDI (without matrix) in negative ion mode. The polymethoxylated flavones were easily ionized by LDI, producing images with higher resolution, but the sesquiterpenes were not observed in spectra. Thus, the application and viability of MALDI imaging for the analyses of protein and secondary metabolites inside trichomes were confirmed, highlighting the importance of optimization parameters. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Nikolaus (Klaus) Fischer on the Occasion of His 80th Birthday)

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11 pages, 2104 KiB

Open AccessArticle

Transparent Nanotubular TiO₂ Photoanodes Grown Directly on FTO Substrates

by Šárka Paušová^1,*, Štěpán Kment², Martin Zlámal¹, Michal Baudys¹, Zdeněk Hubička² and Josef Krýsa^1,*

¹ University of Chemistry and Technology Prague, Technická 5, 166 28 Prague 6, Czech Republic

² Palacký University, RCPTM, Joint Laboratory of Optics, 17. Listopadu 12, 771 46 Olomouc, Czech Republic

Molecules 2017, 22(5), 775; https://doi.org/10.3390/molecules22050775 - 10 May 2017

Cited by 9 | Viewed by 5460

Abstract

This work describes the preparation of transparent TiO₂ nanotube (TNT) arrays on fluorine-doped tin oxide (FTO) substrates. An optimized electrolyte composition (0.2 mol dm⁻³ NH₄F and 4 mol dm⁻³ H₂O in ethylene glycol) was used for [...] Read more.

This work describes the preparation of transparent TiO₂ nanotube (TNT) arrays on fluorine-doped tin oxide (FTO) substrates. An optimized electrolyte composition (0.2 mol dm⁻³ NH₄F and 4 mol dm⁻³ H₂O in ethylene glycol) was used for the anodization of Ti films with different thicknesses (from 100 to 1300 nm) sputtered on the FTO glass substrates. For Ti thicknesses 600 nm and higher, anodization resulted in the formation of TNT arrays with an outer nanotube diameter around 180 nm and a wall thickness around 45 nm, while for anodized Ti thicknesses of 100 nm, the produced nanotubes were not well defined. The transmittance in the visible region (λ = 500 nm) varied from 90% for the thinnest TNT array to 65% for the thickest TNT array. For the fabrication of transparent TNT arrays by anodization, the optimal Ti thickness on FTO was around 1000 nm. Such fabricated TNT arrays with a length of 2500 nm exhibit stable photocurrent densities in aqueous electrolytes (~300 µA cm⁻² at potential 0.5 V vs. Ag/AgCl). The stability of the photocurrent response and a sufficient transparency (≥65%) enables the use of transparent TNT arrays in photoelectrochemical applications when the illumination from the support/semiconductor interface is a necessary condition and the transmitted light can be used for another purpose (photocathode or photochemical reaction in the electrolyte). Full article

(This article belongs to the Special Issue Photon-involving Purification of Water and Air)

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11 pages, 3023 KiB

Open AccessArticle

Application of Soluplus to Improve the Flowability and Dissolution of Baicalein Phospholipid Complex

by Junting Fan¹, Yunhao Dai^2,3, Hongxue Shen³, Jianming Ju^2,3,* and Zhiying Zhao^4,*

¹ School of Pharmacy, Nanjing Medical University, Nanjing 211166, China

² Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese, Nanjing 210028, China

³ Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China

⁴ State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China

Molecules 2017, 22(5), 776; https://doi.org/10.3390/molecules22050776 - 11 May 2017

Cited by 22 | Viewed by 7427

Abstract

In this study, a novel ternary complex system (TCS) composed of baicalein, phospholipids, and Soluplus was prepared to improve the flowability and dissolution for baicalein phospholipid complex (BPC). TCS was characterized using differential scanning calorimetry (DSC), infrared spectroscopy (IR), powder X-ray diffraction (PXRD), [...] Read more.

In this study, a novel ternary complex system (TCS) composed of baicalein, phospholipids, and Soluplus was prepared to improve the flowability and dissolution for baicalein phospholipid complex (BPC). TCS was characterized using differential scanning calorimetry (DSC), infrared spectroscopy (IR), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The flowability, solubility, oil–water partition coefficient, in vitro dissolution, and in vivo pharmacokinetics of the system were also evaluated. DSC, IR, PXRD, and SEM data confirmed that the crystal form of baicalein disappeared in BPC and TCS. Furthermore, the angle of repose of TCS of 35° indicated an improvement in flowability, and solubility increased by approximately eight-fold in distilled water when TCS was compared with BPC (41.00 ± 4.89 μg/mL vs. 5.00 ± 0.16 μg/mL). Approximately 91.24% of TCS was released at the end of 60 min in 0.5% SDS (pH = 6.8), which suggested that TCS could improve the dissolution velocity and extent. Moreover, TCS exhibited a considerable enhancement in bioavailability with higher peak plasma concentration (25.55 μg/mL vs. 6.05 μg/mL) and increased AUC_0–∞ (62.47 μg·h/mL vs. 50.48 μg·h/mL) with 123.75% relative bioavailability compared with BPC. Thus, Soluplus achieved the purpose of improving the flowability and solubility of baicalein phospholipid complexes. The application of Soluplus to phospholipid complexes has great potential. Full article

(This article belongs to the Collection Poorly Soluble Drugs)

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12 pages, 2301 KiB

Open AccessArticle

Crude Ecklonia cava Flake Extracts Attenuate Inflammation through the Regulation of TLR4 Signaling Pathway in LPS-Induced RAW264.7 Cells

by Ji-Hyun Hwang^†, Kui-Jin Kim^† and Boo-Yong Lee^*

¹ Department of Food Science and Biotechnology, CHA University, Seongnam, Gyeonggi 463-400, Korea

^† These authors contributed equally to this work.

Molecules 2017, 22(5), 777; https://doi.org/10.3390/molecules22050777 - 10 May 2017

Cited by 13 | Viewed by 5293

Abstract

We investigated the beneficial effects of the crude Ecklonia cava flake (CEF), which is a residual product after polyphenol extraction from Ecklonia cava, on inflammation in LPS-stimulated RAW264.7 cells. A group of five different CEF extracts was obtained by a preparation process [...] Read more.

We investigated the beneficial effects of the crude Ecklonia cava flake (CEF), which is a residual product after polyphenol extraction from Ecklonia cava, on inflammation in LPS-stimulated RAW264.7 cells. A group of five different CEF extracts was obtained by a preparation process using water, hydrochloric acid or temperature. We observed that large-size (>19 kDa) CEF extract, which was extracted with water at 95 °C (CEF-W, 95 °C), suppressed the production of inflammatory cytokines by inhibiting its mRNA expression in LPS-induced RAW264.7 cells. TLR4 signaling involvements were negatively regulated by CEF-W, 95 °C. CEF-W, 95 °C repressed the translocation of NF-κB from cytoplasm into nucleus in LPS-induced RAW264.7 cells. CEF-W, 95 °C attenuated the phosphorylation of TBK1 and IRF3 by inhibiting the phosphorylation of ERK. Taken together, we demonstrated that large-size CEF-W, 95 °C may act as a negative regulator of inflammation through the suppression of TLR4 signaling constituents in LPS-induced RAW264.7 cells. Full article

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

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11 pages, 715 KiB

Open AccessArticle

Chemical Composition of Laurencia obtusa Extract and Isolation of a New C₁₅-Acetogenin

by Hélène Esselin¹, Sylvain Sutour¹, Joana Liberal^2,3, Maria Teresa Cruz², Ligia Salgueiro², Benjamin Siegler⁴, Ingrid Freuze⁴, Vincent Castola¹, Mathieu Paoli¹, 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 CNC.IBILI/Faculty of Pharmacy, University of Coimbra, Health Sciences Campus, Azinhaga de S. Comba, 3000-548 Coimbra, Portugal

³ Escola Superior de Saúde Dr. Lopes Dias, Instituto Politécnico de Castelo Branco, Campus da Talagueira, 6000-767 Castelo Branco, Portugal

⁴ Plateforme d’Ingénierie et d’Analyses Moléculaires, Université d’Angers, UFR Sciences, 49000 Angers, France

Molecules 2017, 22(5), 779; https://doi.org/10.3390/molecules22050779 - 11 May 2017

Cited by 13 | Viewed by 5061

Abstract

A new C₁₅-acetogenin, sagonenyne (20), exhibiting an unusual single tetrahydropyran ring was isolated from an ethyl acetate extract of Laurencia obtusa collected on the Corsican coastline. Its structure was established by detailed NMR spectroscopic analysis, mass spectrometry, and comparison [...] Read more.

A new C₁₅-acetogenin, sagonenyne (20), exhibiting an unusual single tetrahydropyran ring was isolated from an ethyl acetate extract of Laurencia obtusa collected on the Corsican coastline. Its structure was established by detailed NMR spectroscopic analysis, mass spectrometry, and comparison with literature data. Twenty-three known compounds were identified in the same extract by means of column chromatography steps, using a ¹³C-NMR computer aided method developed in our laboratory. In addition to sesquiterpenes, which represent the main chemical class of this extract, diterpenes, sterols, and C₁₅-acetogenins were identified. The crude extract was submitted to a cytotoxicity assay and was particularly active against THP-1 cells, a human leukemia monocytic cell line. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 4400 KiB

Open AccessArticle

Inclusion Complexes of a New Family of Non-Ionic Amphiphilic Dendrocalix[4]arene and Poorly Water-Soluble Drugs Naproxen and Ibuprofen

by Khalid Khan^1,*

, Syed Lal Badshah¹

, Nasir Ahmad¹, Haroon Ur Rashid²

and Yahia Mabkhot^3,*

¹ Department of Chemistry, Islamia College University, Peshawar 25120, Khyber Pukhtunkhwa, Pakistan

² Department of Chemistry, Sarhad University of Science and Technology, Peshawar 25120, Khyber Pukhtunkhwa, Pakistan

³ Department of Chemistry, College of Science, King Saud University, Riyadh 11495, Saudi Arabia

Molecules 2017, 22(5), 783; https://doi.org/10.3390/molecules22050783 - 11 May 2017

Cited by 15 | Viewed by 5618

Abstract

The inclusion complexes of a new family of nonionic amphiphilic calix[4]arenes with the anti-inflammatory hydrophobic drugs naproxen (NAP) and ibuprofen (IBP) were investigated. The effects of the alkyl chain’s length and the inner core of calix[4]arenes on the interaction of the two drugs [...] Read more.

The inclusion complexes of a new family of nonionic amphiphilic calix[4]arenes with the anti-inflammatory hydrophobic drugs naproxen (NAP) and ibuprofen (IBP) were investigated. The effects of the alkyl chain’s length and the inner core of calix[4]arenes on the interaction of the two drugs with the calix[4]arenes were explored. The inclusion complexes of Amphiphiles 1a–c with NAP and IBP increased the solubility of these drugs in aqueous media. The interaction of 1a–c with the drugs in aqueous media was investigated through fluorescence, molecular modeling, and ¹H-NMR analysis. TEM studies further supported the formation of inclusion complexes. The length of lipophilic alkyl chains and the intrinsic cyclic nature of cailx[4]arene derivatives 1a–c were found to have a significant impact on the solubility of NAP and IBP in pure water. Full article

(This article belongs to the Special Issue Calixarenes, Pillararenes, and Cucurbiturils)

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16 pages, 1683 KiB

Open AccessArticle

Ortho-Nitro Effect on the Diastereoselective Control in Sulfa-Staudinger and Staudinger Cycloadditions

by Zhanhui Yang

, Hassane Abdellaoui, Wei He and Jiaxi Xu^*

State Key Laboratory of Chemical Resource Engineering, Department of Organic Chemistry, Faculty of Science, Beijing University of Chemical Technology, Beijing 100029, China

Molecules 2017, 22(5), 784; https://doi.org/10.3390/molecules22050784 - 12 May 2017

Cited by 7 | Viewed by 5477

Abstract

The ortho-nitro effect was discovered in sulfa-Staudinger cycloadditions of ethoxycarbonylsulfene with linear imines. When an ortho-nitro group is present at the C-aryl substituents of linear imines, the sulfa-Staudinger cycloadditions deliver cis-β-sultams in considerable amounts, together with the predominant trans [...] Read more.

The ortho-nitro effect was discovered in sulfa-Staudinger cycloadditions of ethoxycarbonylsulfene with linear imines. When an ortho-nitro group is present at the C-aryl substituents of linear imines, the sulfa-Staudinger cycloadditions deliver cis-β-sultams in considerable amounts, together with the predominant trans-β-sultams. In other cases, the above sulfa-Staudinger cycloadditions give rise to trans-β-sultams exclusively. Further mechanistic rationalization discloses that the ortho-nitro effect is attributed to its strong electron-withdrawing inductive effect. Similarly, the ortho-nitro effect also exists in Staudinger cycloadditions of ethoxycarbonyl ketene with the imines. The current research provides further insights into the diastereoselective control in sulfa-Staudinger and Staudinger cycloadditions. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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15 pages, 7381 KiB

Open AccessArticle

Design, Synthesis, Molecular Docking Analysis, and Carbonic Anhydrase IX Inhibitory Evaluations of Novel N-Substituted-β-d-Glucosamine Derivatives that Incorporate Benzenesulfonamides

by Feng-Ran Li, Zhan-Fang Fan, Su-Jiao Qi, Yan-Shi Wang, Jian Wang, Yang Liu^*

and Mao-Sheng Cheng^*

Key Laboratory of Structure-Based Drugs Design and Discovery (Ministry of Education), School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China

Molecules 2017, 22(5), 785; https://doi.org/10.3390/molecules22050785 - 12 May 2017

Cited by 19 | Viewed by 5873

Abstract

A series of novel N-substituted-β-d-glucosamine derivatives that incorporate benzenesulfonamides were designed using a fragment-based drug design strategy. Each derivative was synthesized and evaluated in vitro for its inhibitory activity against human carbonic anhydrase (hCA) IX; several derivatives displayed [...] Read more.

A series of novel N-substituted-β-d-glucosamine derivatives that incorporate benzenesulfonamides were designed using a fragment-based drug design strategy. Each derivative was synthesized and evaluated in vitro for its inhibitory activity against human carbonic anhydrase (hCA) IX; several derivatives displayed desirable potency profiles against this enzyme. The molecular docking studies provided the design rationale and predicted potential binding modes for carbonic anhydrase (CA) IX and three target compounds, including the most potent inhibitor, compound 7f (IC₅₀ = 10.01 nM). Moreover, the calculated Log P (cLog P) values showed that all the compounds tended to be hydrophilic. In addition, topological polar surface area (TPSA) value-based predictions highlighted the selectivity of these carbohydrate-based inhibitors for membrane-associated CA IX. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 5131 KiB

Open AccessArticle

Anti-Helicobacter pylori Activity of Isocoumarin Paepalantine: Morphological and Molecular Docking Analysis

by João Paulo L. Damasceno¹, Ricardo P. Rodrigues¹, Rita De Cássia R. Gonçalves^1,2 and Rodrigo R. Kitagawa^1,2,*

¹ Graduate Program in Pharmaceutical Sciences, Federal University of Espirito Santo–UFES, Marechal Campos Av., 1468, Vitoria 29043-900, ES, Brazil

² Department of Pharmaceutical Sciences, Federal University of Espirito Santo–UFES, Marechal Campos Av., 1468, Vitoria 29043-900, ES, Brazil

Molecules 2017, 22(5), 786; https://doi.org/10.3390/molecules22050786 - 12 May 2017

Cited by 22 | Viewed by 6200

Abstract

The Helicobacter pylori bacterium is one of the main causes of chronic gastritis, peptic ulcers, and even gastric cancer. It affects an average of half of the world population. Its difficult eradication depends upon multi-drug therapy. Since its classification as a group 1 [...] Read more.

The Helicobacter pylori bacterium is one of the main causes of chronic gastritis, peptic ulcers, and even gastric cancer. It affects an average of half of the world population. Its difficult eradication depends upon multi-drug therapy. Since its classification as a group 1 carcinogenic by International Agency for Research on Cancer (IARC), the importance of H. pylori eradication has obtained a novel meaning. There is considerable interest in alternative therapies for the eradication of H. pylori using compounds from a wide range of natural products. In the present study, we investigated the antibacterial property of the isocoumarin paepalantine against H. pylori and it exhibited significant anti-H. pylori activity at a minimum inhibitory concentration (MIC) of 128 μg/mL and at a minimum bactericidal concentration (MBC) of 256 μg/mL. The scanning electron microscopy (SEM) revealed significant morphological changes of the bacterial cell as a response to a sub-MIC of paepalantine, suggesting a penicillin-binding protein (PBP) inhibition. Computational studies were carried out in order to study binding modes for paepalantine in PBP binding sites, exploring the active and allosteric sites. The data from the present study indicates that paepalantine exhibits significant anti-H. pylori activity, most likely by inhibiting membrane protein synthesis. Full article

(This article belongs to the Section Natural Products Chemistry)

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17 pages, 8885 KiB

Open AccessArticle

Gubenyiliu II Inhibits Breast Tumor Growth and Metastasis Associated with Decreased Heparanase Expression and Phosphorylation of ERK and AKT Pathways

by Yi Zhang¹, Gan-Lin Zhang^1,*, Xu Sun¹, Ke-Xin Cao¹, Ya-Wen Shang², Mu-Xin Gong²

, Cong Ma¹, Nan Nan¹, Jin-Ping Li^1,3, Ming-Wei Yu¹, Guo-Wang Yang¹ and Xiao-Min Wang^1,*

¹ Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China

² School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China

³ Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Uppsala 75123, Sweden

Molecules 2017, 22(5), 787; https://doi.org/10.3390/molecules22050787 - 15 May 2017

Cited by 12 | Viewed by 6899

Abstract

Gubenyiliu II (GYII), a Traditional Chinese Medicine (TCM) formula used in our hospital, has shown beneficial effects in cancer patients. In this study, we investigated the molecular mechanisms underlying the beneficial effects of GYII on murine breast cancer models. GYII showed significant inhibitory [...] Read more.

Gubenyiliu II (GYII), a Traditional Chinese Medicine (TCM) formula used in our hospital, has shown beneficial effects in cancer patients. In this study, we investigated the molecular mechanisms underlying the beneficial effects of GYII on murine breast cancer models. GYII showed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model. Additionally, GYII suppressed the proliferation of 4T1 and MCF-7 cells in a dose-dependent manner. A better inhibitory effect on 4T1 cell proliferation and migration was found in the decomposed recipes (DR) of GYII. Moreover, heparanase expression and the degree of angiogenesis were reduced in tumor tissues. Western blot analysis showed decreased expression of heparanase and growth factors in the cells treated with GYII and its decomposed recipes (DR2 and DR3), and thereby a reduction in the phosphorylation of extracellular signal-regulated kinase (ERK) and serine-threonine kinase (AKT). These results suggest that GYII exerts anti-tumor growth and anti-metastatic effects in the murine breast cancer model. The anti-tumor activity of GYII and its decomposed recipes is, at least partly, associated with decreased heparanase and growth factor expression, which subsequently suppressed the activation of the ERK and AKT pathways. Full article

(This article belongs to the Special Issue Herbal Remedies Meet Modern Day Medicine: Challenges and Opportunities)

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16 pages, 3633 KiB

Open AccessArticle

Design, Synthesis and Anti-Proliferative Activities of 2,6-Substituted Thieno[3,2-d]pyrimidine Derivatives Containing Electrophilic Warheads

by Qiumeng Zhang¹, Zonglong Hu², Qianqian Shen², Yi Chen^2,* and Wei Lu^1,*

¹ School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China

² Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

Molecules 2017, 22(5), 788; https://doi.org/10.3390/molecules22050788 - 12 May 2017

Cited by 5 | Viewed by 6683

Abstract

Thieno[3,2-d]pyrimidine as an effective pharmacophore has been extensively studied. However, its 2,6-substituted derivatives are rarely reported. In the present study, eighteen 2,6-substituted thieno[3,2-d]pyrimidine derivatives containing electrophilic warheads were designed based on the first known Fibroblast growth factor receptor-4 (FGFR4) [...] Read more.

Thieno[3,2-d]pyrimidine as an effective pharmacophore has been extensively studied. However, its 2,6-substituted derivatives are rarely reported. In the present study, eighteen 2,6-substituted thieno[3,2-d]pyrimidine derivatives containing electrophilic warheads were designed based on the first known Fibroblast growth factor receptor-4 (FGFR4) inhibitor Blu9931. Unexpectedly, all of the derivatives exhibited negligible activity against FGFR4. However, most of the target compounds exhibited antiproliferative activities against four human cancer cell lines, including A431, NCI-H1975, Ramos and SNU-16. Compound 12 showed the most potent antiproliferative activities on the above four cell lines with IC₅₀ values of 1.4 μM, 1.2 μM, 0.6 μM, and 2.6 μM, respectively. Additionally, the antiproliferative activity of 12 against MDA-MB-221 proved that 12 had the selectivity towards certain tumor cell lines. Furthermore, preliminary structure-activity relationship analysis was discussed based on the experimental data. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 2391 KiB

Open AccessArticle

Modes of Cell Death Induced by Photodynamic Therapy Using Zinc Phthalocyanine in Lung Cancer Cells Grown as a Monolayer and Three-Dimensional Multicellular Spheroids

by Sello L. Manoto, Nicolette Houreld

, Natasha Hodgkinson and Heidi Abrahamse^*

Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein 2028, South Africa

Molecules 2017, 22(5), 791; https://doi.org/10.3390/molecules22050791 - 16 May 2017

Cited by 14 | Viewed by 7999

Abstract

Photodynamic therapy (PDT) involves interaction of a photosensitizer, light, and molecular oxygen which produces singlet oxygen and subsequent tumour eradication. The development of second generation photosensitizers, such as phthalocyanines, has improved this technology. Customary monolayer cell culture techniques are, unfortunately, too simple to [...] Read more.

Photodynamic therapy (PDT) involves interaction of a photosensitizer, light, and molecular oxygen which produces singlet oxygen and subsequent tumour eradication. The development of second generation photosensitizers, such as phthalocyanines, has improved this technology. Customary monolayer cell culture techniques are, unfortunately, too simple to replicate treatment effects in vivo. Multicellular tumour spheroids may provide a better alternative since they mimic aspects of the human tumour environment. This study aimed to profile 84 genes involved in apoptosis following treatment with PDT on lung cancer cells (A549) grown in a monolayer versus three-dimensional multicellular tumour spheroids (250 and 500 μm). Gene expression profiling was performed 24 h post irradiation (680 nm; 5 J/cm²) with zinc sulfophthalocyanine (ZnPcS_mix) to determine the genes involved in apoptotic cell death. In the monolayer cells, eight pro-apoptotic genes were upregulated, and two were downregulated. In the multicellular tumour spheroids (250 µm) there was upregulation of only 1 gene while there was downregulation of 56 genes. Apoptosis in the monolayer cultured cells was induced via both the intrinsic and extrinsic apoptotic pathways. However, in the multicellular tumour spheroids (250 and 500 µm) the apoptotic pathway that was followed was not conclusive. Full article

(This article belongs to the Special Issue Porphyrins and Phthalocyanines: Synthesis, Properties and Applications)

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10 pages, 981 KiB

Open AccessArticle

¹¹C-Labeling of Aryl Ketones as Candidate Histamine Subtype-3 Receptor PET Radioligands through Pd(0)-Mediated ¹¹C-Carbonylative Coupling

by Fabrice G. Siméon, William J. Culligan, Shuiyu Lu

and Victor W. Pike^*

Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1003, USA

Molecules 2017, 22(5), 792; https://doi.org/10.3390/molecules22050792 - 12 May 2017

Cited by 6 | Viewed by 4392

Abstract

Pd(0)-mediated coupling between iodoarenes, [¹¹C]carbon monoxide and aryltributylstannanes has been used to prepare simple model [¹¹C]aryl ketones. Here, we aimed to label four 2-aminoethylbenzofuran chemotype based molecules ([¹¹C]1–4) in the carbonyl position, as [...] Read more.

Pd(0)-mediated coupling between iodoarenes, [¹¹C]carbon monoxide and aryltributylstannanes has been used to prepare simple model [¹¹C]aryl ketones. Here, we aimed to label four 2-aminoethylbenzofuran chemotype based molecules ([¹¹C]1–4) in the carbonyl position, as prospective positron emission tomography (PET) radioligands for the histamine subtype 3 receptor (H3R) by adapting this methodology with use of aryltrimethylstannanes. Radiosynthesis was successfully performed on a platform equipped with a mini-autoclave and a liquid handling robotic arm, within a lead-shielded hot-cell. Candidate radioligands were readily formulated in saline containing ethanol (10%, v/v) and ascorbic acid (0.5 mg/10 mL). Yields for preclinical use were in the range of 5–9%, decay-corrected from cyclotron-produced [¹¹C]CO₂ and molar activities were >115 GBq/µmol at end of synthesis. Radiochemical purities exceeded >97%. Full article

(This article belongs to the Section Medicinal Chemistry)

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22 pages, 1580 KiB

Open AccessArticle

Synthesis, Biological Activity and Preliminary in Silico ADMET Screening of Polyamine Conjugates with Bicyclic Systems

by Marta Szumilak¹

, Malgorzata Galdyszynska², Kamila Dominska², Irena I. Bak-Sypien³, Anna Merecz-Sadowska³, Andrzej Stanczak¹, Boleslaw T. Karwowski^3,* and Agnieszka W. Piastowska-Ciesielska^2,4

¹ Department of Hospital Pharmacy, Faculty of Pharmacy, Medical University of Lodz, 1 Muszynskiego Street, 90-151 Lodz, Poland

² Department of Comparative Endocrinology, Medical University of Lodz, 7/9 Zeligowskiego Street, 90-752 Lodz, Poland

³ Food Science Department, Faculty of Pharmacy, Medical University of Lodz, 1 Muszynskiego Street, 90-151 Lodz, Poland

⁴ Laboratory of Cell Cultures and Genomic Analysis, Medical University of Lodz, 7/9 Zeligowskiego Street, Lodz 90-752, Poland

Molecules 2017, 22(5), 794; https://doi.org/10.3390/molecules22050794 - 12 May 2017

Cited by 14 | Viewed by 5574

Abstract

Polyamine conjugates with bicyclic terminal groups including quinazoline, naphthalene, quinoline, coumarine and indole have been obtained and their cytotoxic activity against PC–3, DU–145 and MCF–7 cell lines was evaluated in vitro. Their antiproliferative potential differed markedly and depended on both their chemical structure [...] Read more.

Polyamine conjugates with bicyclic terminal groups including quinazoline, naphthalene, quinoline, coumarine and indole have been obtained and their cytotoxic activity against PC–3, DU–145 and MCF–7 cell lines was evaluated in vitro. Their antiproliferative potential differed markedly and depended on both their chemical structure and the type of cancer cell line. Noncovalent DNA-binding properties of the most active compounds have been examined using ds–DNA thermal melting studies and topo I activity assay. The promising biological activity, DNA intercalative binding mode and favorable drug-like properties of bis(naphthalene-2-carboxamides) make them a good lead for further development of potential anticancer drugs. Full article

(This article belongs to the Special Issue Nucleic Acid Chemistry and Nucleic Acid Drugs: A Themed Issue in Honor of Professor Lihe Zhang on the Occasion of His 80th Birthday)

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11 pages, 6262 KiB

Open AccessArticle

Nine Different Chemical Species and Action Mechanisms of Pancreatic Lipase Ligands Screened Out from Forsythia suspensa Leaves All at One Time

by Tinggui Chen^*

, Yayun Li and Liwei Zhang

Institute of Molecular Science, Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan 030006, China

Molecules 2017, 22(5), 795; https://doi.org/10.3390/molecules22050795 - 12 May 2017

Cited by 23 | Viewed by 5309

Abstract

It is difficult to screen out as many active components as possible from natural plants all at one time. In this study, subfractions of Forsythia suspensa leaves were firstly prepared; then, their inhibitive abilities on pancreatic lipase were tested; finally, the highest inhibiting [...] Read more.

It is difficult to screen out as many active components as possible from natural plants all at one time. In this study, subfractions of Forsythia suspensa leaves were firstly prepared; then, their inhibitive abilities on pancreatic lipase were tested; finally, the highest inhibiting subfraction was screened by self-made immobilized pancreatic lipase. Results showed that nine ligands, including eight inhibitors and one promotor, were screened out all at one time. They were three flavonoids (rutin, IC₅₀: 149 ± 6.0 μmol/L; hesperidin, 52.4 μmol/L; kaempferol-3-O-rutinoside, isolated from F. suspensa leaves for the first time, IC₅₀ notably reached 2.9 ± 0.5 μmol/L), two polyphenols (chlorogenic acid, 3150 ± 120 μmol/L; caffeic acid, 1394 ± 52 μmol/L), two lignans (phillyrin, promoter; arctigenin, 2129 ± 10.5 μmol/L), and two phenethyl alcohol (forsythiaside A, 2155 ± 8.5 μmol/L; its isomer). Their action mechanisms included competitive inhibition, competitive promotion, noncompetitive inhibition, and uncompetitive inhibition. In sum, using the appropriate methods, more active ingredients can be simply and quickly screened out all at one time from a complex natural product system. In addition, F. suspensa leaves contain numerous inhibitors of pancreatic lipase. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 546 KiB

Open AccessArticle

Alkamides from Anacyclus pyrethrum L. and Their in Vitro Antiprotozoal Activity

by Julia B. Althaus^1,†, Claudine Malyszek^1,†, Marcel Kaiser^2,3, Reto Brun^2,3 and Thomas J. Schmidt^1,*

¹ Institut für Pharmazeutische Biologie und Phytochemie (IPBP), University of Münster, PharmaCampus, Corrensstraße 48, Münster D-48149, Germany

² Swiss Tropical and Public Health Institute (Swiss TPH), Socinstraße 57, Basel CH-4002, Switzerland

³ University of Basel, Petersplatz 1, Basel CH-4003, Switzerland

^† Part of doctoral thesis of J.B.A. and MSc thesis of C.M.

Molecules 2017, 22(5), 796; https://doi.org/10.3390/molecules22050796 - 12 May 2017

Cited by 23 | Viewed by 6357

Abstract

In our ongoing study to evaluate the antiprotozoal activity of alkamides from Asteraceae, a dichloromethane extract from the roots of Anacyclus pyrethrum L. showed a moderate in vitro activity against the NF54 strain of Plasmodium falciparum and against Leishmania donovani (amastigotes, MHOM/ET/67/L82 strain). [...] Read more.

In our ongoing study to evaluate the antiprotozoal activity of alkamides from Asteraceae, a dichloromethane extract from the roots of Anacyclus pyrethrum L. showed a moderate in vitro activity against the NF54 strain of Plasmodium falciparum and against Leishmania donovani (amastigotes, MHOM/ET/67/L82 strain). Seven pure alkamides and a mixture of two further alkamides were isolated by column chromatography followed by preparative high performance liquid chromatography. The alkamides were identified by mass- and NMR-spectroscopic methods as tetradeca-2E,4E-dien-8,10-diynoic acid isobutylamide (anacycline, 1), deca-2E,4E-dienoic acid isobutylamide (pellitorine, 2), deca-2E,4E,9-trienoic acid isobutylamide (3), deca-2E,4E-dienoic acid 2-phenylethylamide (4), undeca-2E,4E-dien-8,10-diynoic acid isopentylamide (5), tetradeca-2E,4E,12Z-trien-8,10-diynoic acid isobutylamide (6), and dodeca-2E,4E-dien acid 4-hydroxy-2-phenylethylamide (7). Two compounds—undeca-2E,4E-dien-8,10-diynoic acid 2-phenylethylamide (8) and deca-2E,4E-dienoic acid 4-hydroxy-2-phenylethylamide (9)—were isolated as an inseparable mixture (1:4). Compounds 3, 4, and 5 were isolated from Anacyclus pyrethrum L. for the first time. While compounds 4 and 5 were previously known from the genus Achillea, compound 3 is a new natural product, to the best of our knowledge. All isolated alkamides were tested in vitro for antiprotozoal activity against Plasmodium falciparum, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, and Leishmania donovani and for cytotoxicity against L6 rat skeletal myoblasts. Full article

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

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10 pages, 7767 KiB

Open AccessArticle

Raspberry-Like Bismuth Oxychloride on Mesoporous Siliceous Support for Sensitive Electrochemical Stripping Analysis of Cadmium

by Yiyan Song¹, Zhihui Xu¹, Xinyu Yu¹, Xueyan Shi², Huijun Jiang², Xiaoming Li³, Yan Kong³, Qin Xu⁴ and Jin Chen^1,5,*

¹ School of Public Health, Nanjing Medical University, Nanjing 211166, China

² School of Pharmacy, Nanjing Medical University, Nanjing 211166, China

³ State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemistry and Chemical Engineering, Nanjing University of Technology, Nanjing 211166, China

⁴ College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou 225002, China

⁵ The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210093, China

Molecules 2017, 22(5), 797; https://doi.org/10.3390/molecules22050797 - 13 May 2017

Cited by 11 | Viewed by 5060

Abstract

BiOCl-SiO₂ KIT-6 composite materials with raspberry-like structures are facilely prepared under hydrothermal conditions. The mesoporous siliceous support of SiO₂ KIT-6-incorporated BiOCl with enlarged yet refined surface morphology characterized by physiochemical methods exhibits an improved electrochemical performance. A sensitive electrochemical detection method [...] Read more.

BiOCl-SiO₂ KIT-6 composite materials with raspberry-like structures are facilely prepared under hydrothermal conditions. The mesoporous siliceous support of SiO₂ KIT-6-incorporated BiOCl with enlarged yet refined surface morphology characterized by physiochemical methods exhibits an improved electrochemical performance. A sensitive electrochemical detection method of cadmium concentration using square wave anodic stripping voltammetry was developed based on BiOCl-SiO₂ KIT-6 composite-modified glassy carbon electrodes, which displayed wide linear ranges of 0.5 to 10 μg/L and 10 to 300 μg/L and a detection limit of 65 ng/L. The sensitive, versatile and eco-friendly sensor was successfully applied for the determination of cadmium-spiked human blood samples. Full article

(This article belongs to the Special Issue Mesoporous Silica in Biomedical Applications)

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12 pages, 3070 KiB

Open AccessArticle

1,4-Naphthoquinone Triggers Nematode Lethality by Inducing Oxidative Stress and Activating Insulin/IGF Signaling Pathway in Caenorhabditis elegans

by Jia Wang^1,2,4,†, Guangzhi Zeng^1,3,†, Xiaobing Huang¹, Zhe Wang^1,2 and Ninghua Tan^1,2,*

¹ State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China

² School of Traditional Chinese Pharmacy and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China

³ YMU-HKBU Joint Laboratory of Traditional Natural Medicine, Yunnan Minzu University, Kunming 650500, China

⁴ University of Chinese Academy of Sciences, Beijing 100049, China

^† These authors contributed equally to this work.

Molecules 2017, 22(5), 798; https://doi.org/10.3390/molecules22050798 - 13 May 2017

Cited by 18 | Viewed by 5760

Abstract

Plant-parasitic nematodes are destructive pathogens causing enormous economic losses worldwide. With the withdrawal of fumigants, organophosphates and carbamates, pathogenic nematode control is more difficult. Phytochemicals are the plant secondary metabolites and are friendly for men and the environment. For developing new nematocidal candidates, [...] Read more.

Plant-parasitic nematodes are destructive pathogens causing enormous economic losses worldwide. With the withdrawal of fumigants, organophosphates and carbamates, pathogenic nematode control is more difficult. Phytochemicals are the plant secondary metabolites and are friendly for men and the environment. For developing new nematocidal candidates, we screened 790 phytochemicals using the model organism Caenorhabditis elegans and found 10 active compounds, 3 of which were further evaluated for their inhibitory activities against egg hatching of C. elegans and J2 Meloidogyne incognita. Among them, 1,4-naphthoquinone (1,4-NQ) was the only compound that could kill more than 50% of targets at 50 μg/mL, prompting us to investigate how 1,4-NQ triggers nematode lethality. In C. elegans, we observed that 1,4-NQ could influence reactive oxygen production, superoxide dismutase activity, and the heat-shock transcription factor (HSF)-1 pathway, which indicated that 1,4-NQ stimulated significant oxidative stress. Furthermore, using quantitative RT-PCR and transgenetic nematodes, we revealed that 1,4-NQ lethality was related to the Insulin/IGF signaling (IIS) pathway, and the effect of 1,4-NQ on IIS pathway related genes indicated that 1,4-NQ could activate this pathway and suppress the expression of DAF-16 target genes. The triggering of oxidative stress and activation of the IIS pathway indicated that 1,4-NQ operates through the generation of oxygen radicals, which can be lethal to C. elegans, thus making it an interesting lead compound for the development of future nematocides. Full article

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12 pages, 4021 KiB

Open AccessArticle

Antigiardial Activity of Podophyllotoxin-Type Lignans from Bursera fagaroides var. fagaroides

by Filiberto Gutiérrez-Gutiérrez¹, Ana María Puebla-Pérez¹, Sirenia González-Pozos², José Manuel Hernández-Hernández³, Armando Pérez-Rangel³, Laura Patricia Alvarez⁴, Gabriela Tapia-Pastrana⁵ and Araceli Castillo-Romero^6,*

¹ Departamento de Química y Farmacobiología, Universidad de Guadalajara, Guadalajara 44430, Jalisco, Mexico

² Unidad de Microscopía Electrónica LaNSE, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México 07360, Mexico

³ Departamento de Biología Celular, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México 07360, Mexico

⁴ Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos, Morelos 62209, Mexico

⁵ Laboratorio de Investigación Biomédica, Hospital Regional de Alta Especialidad de Oaxaca, Oaxaca 71256, Mexico

⁶ Departamento de Microbiología y Patología, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico

Molecules 2017, 22(5), 799; https://doi.org/10.3390/molecules22050799 - 13 May 2017

Cited by 14 | Viewed by 5083

Abstract

Giardiasis, a diarrheal disease, is highly prevalent in developing countries. Several drugs are available for the treatment of this parasitosis; unfortunately, all of them have variable efficacies and adverse effects. Bursera fagaroides has been known for its anti-inflammatory and antidiarrheal properties in Mexican [...] Read more.

Giardiasis, a diarrheal disease, is highly prevalent in developing countries. Several drugs are available for the treatment of this parasitosis; unfortunately, all of them have variable efficacies and adverse effects. Bursera fagaroides has been known for its anti-inflammatory and antidiarrheal properties in Mexican traditional medicine. We investigated the in vitro anti-giardial activities of four podophyllotoxin-type lignans from Bursera fagaroides var. fagaroides, namely, 5′-desmethoxy-β-peltatin-A-methylether (5-DES), acetylpodophyllotoxin (APOD), burseranin (BUR), and podophyllotoxin (POD). All lignans affected the Giardia adhesion and electron microscopy images revealed morphological alterations in the caudal region, ventral disk, membrane, and flagella, to different extents. Only 5-DES, APOD, and POD caused growth inhibition. Using the Caco-2 human cell line as a model of the intestinal epithelium, we demonstrated that APOD displayed direct antigiardial killing activity and low toxicity on Caco-2 cells. This finding makes it an attractive potential starting point for new antigiardial drugs. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 2044 KiB

Open AccessArticle

The Hypnotic, Anxiolytic, and Antinociceptive Profile of a Novel µ-Opioid Agonist

by Guilherme Carneiro Montes¹, Bianca Nascimento Monteiro Da Silva², Bismarck Rezende¹, Roberto Takashi Sudo^1,3, Vitor Francisco Ferreira⁴, Fernando De Carvalho da Silva⁴

, Angelo Da Cunha Pinto^2,3, Bárbara Vasconcellos Da Silva² and Gisele Zapata-Sudo^1,3,*

¹ Programa de Pesquisa em Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro RJ 21941-902, Brazil

² Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro RJ 21941-909, Brazil

³ Instituto Nacional de Ciência e Tecnologia de Fármacos e Medicamentos (INCT-INOFAR), Rio de Janeiro RJ 21941-971, Brazil

⁴ Instituto de Química, Universidade Federal Fluminense, Niterói RJ 24020-150, Brazil

Molecules 2017, 22(5), 800; https://doi.org/10.3390/molecules22050800 - 16 May 2017

Cited by 20 | Viewed by 5067

Abstract

5′-4-Alkyl/aryl-1H-1,2,3-triazole derivatives PILAB 1–12 were synthesized and a pharmacological screening of these derivatives was performed to identify a possible effect on the Central Nervous System (CNS) and to explore the associated mechanisms of action. The mice received a peritoneal [...] Read more.

5′-4-Alkyl/aryl-1H-1,2,3-triazole derivatives PILAB 1–12 were synthesized and a pharmacological screening of these derivatives was performed to identify a possible effect on the Central Nervous System (CNS) and to explore the associated mechanisms of action. The mice received a peritoneal injection (100 µmol/kg) of each of the 12 PILAB derivatives 10 min prior to the injection of pentobarbital and the mean hypnosis times were recorded. The mean hypnosis time increased for the mice treated with PILAB 8, which was prevented when mice were administered CTOP, a µ-opioid antagonist. Locomotor and motor activities were not affected by PILAB 8. The anxiolytic effect of PILAB 8 was evaluated next in an elevated-plus maze apparatus. PILAB 8 and midazolam increased a percentage of entries and spent time in the open arms of the apparatus compared with the control group. Conversely, a decrease in the percentages of entries and time spent in the closed arms were observed. Pretreatment with naloxone, a non-specific opioid antagonist, prior to administration of PILAB 8 exhibited a reverted anxiolytic effect. PILAB 8 exhibited antinociceptive activity in the hot plate test, and reduced reactivity to formalin in the neurogenic and the inflammatory phases. These data suggest that PILAB 8 can activate µ-opioid receptors to provoke antinociceptive and anti-inflammatory effects in mice. Full article

(This article belongs to the Section Medicinal Chemistry)

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21 pages, 12540 KiB

Open AccessArticle

Alcohols as Substrates and Solvents for the Construction of 3-Alkoxylated-2-Oxindoles by Direct Alkoxylation of 3-Halooxindoles

by Bing Lin^1,†, Zhi-Yong Chen^1,†, Huan-Huan Liu¹, Qi-Di Wei¹, Ting-Ting Feng¹, Ying Zhou^1,*, Can Wang¹, Xiong-Li Liu^1,* and Wei-Cheng Yuan²

¹ Guizhou Medicine Edicine Edible Plant Resources Research and Development Center, College of Pharmacy, Guizhou University, Guiyang 550025, China

² Key Laboratory for Asymmetric Synthesis & Chirotechnology of Sichuan Province, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China

^† These two authors contributed equally to this work.

Molecules 2017, 22(5), 801; https://doi.org/10.3390/molecules22050801 - 13 May 2017

Cited by 6 | Viewed by 4449

Abstract

Described herein is an environmentally benign method for the synthesis of multisubstituted 3-alkoxylated-2-oxindoles 3 via direct alkoxylation of 3-halooxindoles 1. A wide variety of such multisubstituted 3-alkoxylated-2-oxindole scaffolds were smoothly obtained in good yields (up to 94%) by heating in an oil [...] Read more.

Described herein is an environmentally benign method for the synthesis of multisubstituted 3-alkoxylated-2-oxindoles 3 via direct alkoxylation of 3-halooxindoles 1. A wide variety of such multisubstituted 3-alkoxylated-2-oxindole scaffolds were smoothly obtained in good yields (up to 94%) by heating in an oil bath at 35 °C for 24 h. A particularly valuable feature of this method was the development of environment-friendly chemistry using alcohols 2 as both the substrates and solvents in the presence of a catalytic amount of base. Full article

(This article belongs to the Section Organic Chemistry)

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11 pages, 1802 KiB

Open AccessCommunication

Optimizing the Readout of Lanthanide-DOTA Complexes for the Detection of Ligand-Bound Copper(I)

by Jill R. Hanna, Christopher Allan, Charlotte Lawrence, Odile Meyer, Neil D. Wilson and Alison N. Hulme^*

EaStCHEM School of Chemistry, The University of Edinburgh, Joseph Black Building, David Brewster Road, Edinburgh EH9 3FJ, UK

Molecules 2017, 22(5), 802; https://doi.org/10.3390/molecules22050802 - 14 May 2017

Cited by 13 | Viewed by 9096

Abstract

The CuAAC ‘click’ reaction was used to couple alkyne-functionalized lanthanide-DOTA complexes to a range of fluorescent antennae. Screening of the antenna components was aided by comparison of the luminescent output of the resultant sensors using data normalized to account for reaction conversion as [...] Read more.

The CuAAC ‘click’ reaction was used to couple alkyne-functionalized lanthanide-DOTA complexes to a range of fluorescent antennae. Screening of the antenna components was aided by comparison of the luminescent output of the resultant sensors using data normalized to account for reaction conversion as assessed by IR. A maximum 82-fold enhanced signal:background luminescence output was achieved using a Eu(III)-DOTA complex coupled to a coumarin-azide, in a reaction which is specific to the presence of copper(I). This optimized complex provides a new lead design for lanthanide-DOTA complexes which can act as irreversible ‘turn-on’ catalytic sensors for the detection of ligand-bound copper(I). Full article

(This article belongs to the Special Issue Women in Organic Chemistry)

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15 pages, 3257 KiB

Open AccessArticle

Effects of Mead Wort Heat Treatment on the Mead Fermentation Process and Antioxidant Activity

by Sławomir Czabaj^1,*

, Joanna Kawa-Rygielska¹, Alicja Z. Kucharska²

and Jarosław Kliks³

¹ Department of Fermentation and Cereals Technology, Wroclaw University of Environmental and Life Sciences, Wrocław 51-630, Poland

² Department of Fruit, Vegetable, and Plant Nutraceutical Technology, Wroclaw University of Environmental and Life Sciences, Wrocław 51-630, Poland

³ Lubuski Centre for Innovation and Agricultural Implementation, Kalsk 66-100, Poland

Molecules 2017, 22(5), 803; https://doi.org/10.3390/molecules22050803 - 14 May 2017

Cited by 40 | Viewed by 7277

Abstract

The effects of mead wort heat treatment on the mead fermentation process and antioxidant activity were tested. The experiment was conducted with the use of two different honeys (multiflorous and honeydew) collected from the Lower Silesia region (Poland). Heat treatment was performed with [...] Read more.

The effects of mead wort heat treatment on the mead fermentation process and antioxidant activity were tested. The experiment was conducted with the use of two different honeys (multiflorous and honeydew) collected from the Lower Silesia region (Poland). Heat treatment was performed with the use of a traditional technique (gently boiling), the more commonly used pasteurization, and without heat treatment (control). During the experiment fermentation dynamics were monitored using high performance liquid chromatography with refractive index detection (HPLC-RID). Total antioxidant capacity (TAC) and total phenolic content (TPC) were estimated for worts and meads using UV/Vis spectrophotometric analysis. The formation of 5-hydroxymethylfurfural (HMF) was monitored by HPLC analyses. Heat treatment had a great impact on the final antioxidant capacity of meads. Full article

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10 pages, 5022 KiB

Open AccessArticle

Evaluation of Efficient and Practical Methods for the Preparation of Functionalized Aliphatic Trifluoromethyl Ethers

by Taras M. Sokolenko¹, Maya I. Dronkina^1,†, Emmanuel Magnier²

, Lev M. Yagupolskii^1,‡ and Yurii L. Yagupolskii^1,3,*

¹ Institute of Organic Chemistry, NAS of Ukraine, Murmans’ka St. 5, Kiev 02660, Ukraine

² Bâtiment Lavoisier, Université de Versailles-Saint-Quentin, 45 Avenue des Etats-Unis, Versailles 78035, France

³ Enamine Ltd, A. Matrosova str. 23, Kiev 01103, Ukraine

^† Retired.

^‡ Passed away.

Molecules 2017, 22(5), 804; https://doi.org/10.3390/molecules22050804 - 14 May 2017

Cited by 8 | Viewed by 6602

Abstract

The “chlorination/fluorination” technique for aliphatic trifluoromethyl ether synthesis was investigated and a range of products with various functional groups was prepared. The results were compared with oxidative desulfurization-fluorination of xanthates with the same structure. Full article

(This article belongs to the Special Issue Tri- and Di-Fluoromethylation and Tri- and Di-Fluoromethylchalcogenation Reactions)

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13 pages, 3492 KiB

Open AccessArticle

Identification and Validation of SAA4 as a Rheumatoid Arthritis Prescreening Marker by Liquid Chromatography Tandem-mass Spectrometry

by AeEun Seok^1,2,†

, Hyun-Jung Lee^3,4,†, Sungeun Lee²

, Jiyeong Lee³

, Sora Mun¹, Arum Park¹, Yeon-Tae Chun^1,5, Jae-Hyeon Lee², Hee-Joung Lim^6,* and Hee-Gyoo Kang^1,3,*

¹ Laboratory of Signal Transduction and Disease Biomarker Discovery, Department of Senior Healthcare, BK21 Plus Program, Graduate School, Eulji University, Daejeon 34824, Korea

² Research Institute of DongDeok Pharmaceutical, Chungcheongbuk-do 27864, Korea

³ Department of Biomedical Laboratory Science, College of Health Sciences, Eulji University, Seongnam-si, Gyeonggi-do 13135, Korea

⁴ Department of Laboratory Medicine, Korea Cancer Center Hospital, Seoul 01812, Korea

⁵ Integrative Research Support Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea

⁶ Forensic Science R&D Lab., Police Science Institute, Chungcheongnam-do 31539, Korea

^† These authors contributed equally.

Molecules 2017, 22(5), 805; https://doi.org/10.3390/molecules22050805 - 14 May 2017

Cited by 18 | Viewed by 5619

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease that progresses into systemic inflammation and joint deformity. RA diagnosis is a complicated procedure, and early diagnostic methods are insufficient. Therefore, in this study, we attempted to identify new markers to improve the accuracy of [...] Read more.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that progresses into systemic inflammation and joint deformity. RA diagnosis is a complicated procedure, and early diagnostic methods are insufficient. Therefore, in this study, we attempted to identify new markers to improve the accuracy of RA prescreening. e identified differentially expressed proteins (DEPs) by using liquid chromatography tandem-mass spectrometry in health-prescreening sera with high rheumatoid factor (RF) values, and compared the findings with those from sera with normal RF values. We identified 93 DEPs; of these, 36 were upregulated, and 57 were downregulated in high-RF sera. Pathway analysis revealed that these DEPs were related to immune responses. Additionally, four DEPs were statistically analyzed by proteomic analysis; of these, SAA4 was significantly validated in individual enzyme-linked immunosorbent assays. Moreover, SAA4 was significantly upregulated in RA patients (n = 40, 66.43 ± 12.97 ng/mL) compared with normal controls (n = 40, 4.79 ± 0.95 ng/mL) and had a higher area under the curve than C-reactive protein. Thus, we identified SAA4 as a protein that was positively correlated with RF and RA. SAA4 may represent a novel prescreening marker for the diagnosis of RA. Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 2006 KiB

Open AccessArticle

Structure-Activity Relationships of Bioengineered Heparin/Heparan Sulfates Produced in Different Bioreactors

by Ha Na Kim, John M. Whitelock and Megan S. Lord^*

Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia

Molecules 2017, 22(5), 806; https://doi.org/10.3390/molecules22050806 - 15 May 2017

Cited by 13 | Viewed by 6852

Abstract

Heparin and heparan sulfate are structurally-related carbohydrates with therapeutic applications in anticoagulation, drug delivery, and regenerative medicine. This study explored the effect of different bioreactor conditions on the production of heparin/heparan sulfate chains via the recombinant expression of serglycin in mammalian cells. Tissue [...] Read more.

Heparin and heparan sulfate are structurally-related carbohydrates with therapeutic applications in anticoagulation, drug delivery, and regenerative medicine. This study explored the effect of different bioreactor conditions on the production of heparin/heparan sulfate chains via the recombinant expression of serglycin in mammalian cells. Tissue culture flasks and continuously-stirred tank reactors promoted the production of serglycin decorated with heparin/heparan sulfate, as well as chondroitin sulfate, while the serglycin secreted by cells in the tissue culture flasks produced more highly-sulfated heparin/heparan sulfate chains. The serglycin produced in tissue culture flasks was effective in binding and signaling fibroblast growth factor 2, indicating the utility of this molecule in drug delivery and regenerative medicine applications in addition to its well-known anticoagulant activity. Full article

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

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8 pages, 1178 KiB

Open AccessArticle

Isolaurenidificin and Bromlaurenidificin, Two New C₁₅-Acetogenins from the Red Alga Laurencia obtusa

by Nahed O. Bawakid¹

, Walied M. Alarif^2,*, Najla A. Alburae³

, Hajer S. Alorfi¹, Khalid O. Al-Footy¹, Sultan S. Al-Lihaibi² and Mohamed A. Ghandourah²

¹ Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia

² Department of Marine Chemistry, Faculty of Marine Sciences, King Abdulaziz University, P.O. Box 80207, Jeddah 21589, Saudi Arabia

³ Department of Biology, Faculty of Sciences, King Abdulaziz University, P.O. Box 80207, Jeddah 21589, Saudi Arabia

Molecules 2017, 22(5), 807; https://doi.org/10.3390/molecules22050807 - 15 May 2017

Cited by 13 | Viewed by 5352

Abstract

Chromatographic fractionation of the CH₂Cl₂/MeOH extract of the Red Sea red alga Laurencia obtusa gave two new hexahydrofuro[3,2-b]furan-based C₁₅-acetogenins, namely, isolaurenidificin (1) and bromlaurenidificin (2). The chemical structures were elucidated based [...] Read more.

Chromatographic fractionation of the CH₂Cl₂/MeOH extract of the Red Sea red alga Laurencia obtusa gave two new hexahydrofuro[3,2-b]furan-based C₁₅-acetogenins, namely, isolaurenidificin (1) and bromlaurenidificin (2). The chemical structures were elucidated based on extensive analyses of their spectral data. Compounds 1 and 2 showed no toxicity (LC₅₀ > 12 mM) using Artemia salina as test organism. Both compounds showed weak cytotoxicity against A549, HepG-2, HCT116, MCF-7, and PC-3 cells, however, they exhibited a relatively potent cytotoxic activity against peripheral blood neutrophils. This can be attributed partly to induction of apoptosis. Full article

(This article belongs to the Collection Bioactive Compounds)

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9 pages, 6332 KiB

Open AccessArticle

The Transcriptome of Type I Murine Astrocytes under Interferon-Gamma Exposure and Remyelination Stimulus

by Anna Kudriaeva^1,†, Vladimir V. Galatenko^2,3,4,†

, Diana V. Maltseva⁴, Nadezhda A. Khaustova⁴, Ekaterina Kuzina^1,‡, Alexander G. Tonevitsky⁵, Alexander Gabibov^1,3,6 and Alexey Belogurov^1,3,6,*

¹ Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia

² Department of Mathematical Analysis, Faculty of Mechanics and Mathematics, Lomonosov Moscow State University, 119991 Moscow, Russia

³ Big Data and Information Retrieval School, Faculty of Computer Science, National Research University Higher School of Economics, 125319 Moscow, Russia

⁴ SRC Bioclinicum, 115088 Moscow, Russia

⁵ P. Hertsen Moscow Oncology Research Institute, 125284 Moscow, Russia

⁶ Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia

^† These authors contributed equally to this work.

^‡ Current address: Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA.

Molecules 2017, 22(5), 808; https://doi.org/10.3390/molecules22050808 - 15 May 2017

Cited by 20 | Viewed by 6510

Abstract

Astrocytes are considered to be an important contributor to central nervous system (CNS) disorders, particularly multiple sclerosis. The transcriptome of these cells is greatly affected by cytokines released by lymphocytes, penetrating the blood–brain barrier—in particular, the classical pro-inflammatory cytokine interferon-gamma (IFNγ). We report [...] Read more.

Astrocytes are considered to be an important contributor to central nervous system (CNS) disorders, particularly multiple sclerosis. The transcriptome of these cells is greatly affected by cytokines released by lymphocytes, penetrating the blood–brain barrier—in particular, the classical pro-inflammatory cytokine interferon-gamma (IFNγ). We report here the transcriptomal profiling of astrocytes treated using IFNγ and benztropine, a putative remyelinization agent. Our findings indicate that the expression of genes involved in antigen processing and presentation in astrocytes are significantly upregulated upon IFNγ exposure, emphasizing the critical role of this cytokine in the redirection of immune response towards self-antigens. Data reported herein support previous observations that the IFNγ-induced JAK-STAT signaling pathway may be regarded as a valuable target for pharmaceutical interventions. 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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17 pages, 11113 KiB

Open AccessArticle

Mitochondria Targeting with Luminescent Rhenium(I) Complexes

by Joanna Skiba¹, Tytus Bernaś², Damian Trzybiński³, Krzysztof Woźniak³

, Giarita Ferraro⁴, Daniela Marasco^5,6,7, Antonello Merlino^4,7

, Marsel Z. Shafikov^8,9, Rafał Czerwieniec^9,10,* and Konrad Kowalski^1,*

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

² Nencki Institute of Experimental Biology, Polish Academy of Sciences, ul. Pasteura 3, 02-093 Warszawa, Poland

³ Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Żwirki i Wigury 101, 02-089 Warszawa, Poland

⁴ Department of Chemical Sciences, University of Naples Federico II, Complesso Univ. di Monte Sant’ Angelo, Via Cintia, I-80126 Napoli, Italy

⁵ Department of Pharmacy, University of Naples Federico II, Via Mezzocannone 16, 80134 Napoli, Italy

⁶ CIRPEB: Centro Interuniversitario di Ricerca sui Peptidi Bioattivi, Via Mezzocannone 16, I-80134 Napoli, Italy

⁷ CNR Institute of Biostructures and Bioimages, Via Mezzocannone 16, I-80134 Napoli, Italy

⁸ Department of Technology of Organic Synthesis, Institute of Chemical Engineering, Ural Federal University, 19 Mira Str., 620002 Ekaterinburg, Russia

⁹ Institut für Physikalische und Theoretische Chemie, Universität Regensburg, Universitätsstraße 31, D-93040 Regensburg, Germany

¹⁰ Lehrstuhl für Anorganische Chemie I, University of Bayreuth, D-95440 Bayreuth, Germany

Molecules 2017, 22(5), 809; https://doi.org/10.3390/molecules22050809 - 15 May 2017

Cited by 27 | Viewed by 7193

Abstract

Two new neutral fac-[Re(CO)₃(phen)L] compounds (1,2), with phen = 1,10-phenanthroline and L = O₂C(CH₂)₅CH₃ or O₂C(CH₂)₄C≡CH, were synthetized in one-pot procedures from fac [...] Read more.

Two new neutral fac-[Re(CO)₃(phen)L] compounds (1,2), with phen = 1,10-phenanthroline and L = O₂C(CH₂)₅CH₃ or O₂C(CH₂)₄C≡CH, were synthetized in one-pot procedures from fac-[Re(CO)₃(phen)Cl] and the corresponding carboxylic acids, and were fully characterized by IR and UV-Vis absorption spectroscopy, ¹H- and ¹³C-NMR, mass spectrometry and X-ray crystallography. The compounds, which display orange luminescence, were used as probes for living cancer HeLa cell staining. Confocal microscopy revealed accumulation of both dyes in mitochondria. To investigate the mechanism of mitochondrial staining, a new non-emissive compound, fac-[Re(CO)₃(phen)L], with L = O₂C(CH₂)₃((C₅H₅)Fe(C₅H₄), i.e., containing a ferrocenyl moiety, was synthetized and characterized (3). 3 shows the same mitochondrial accumulation pattern as 1 and 2. Emission of 3 can only be possible when ferrocene-containing ligand dissociates from the metal center to produce a species containing the luminescent fac[Re(CO)₃(phen)]⁺ core. The release of ligands from the Re center was verified in vitro through the conjugation with model proteins. These findings suggest that the mitochondria accumulation of compounds 1–3 is due to the formation of luminescent fac-[Re(CO)₃(phen)]⁺ products, which react with cellular matrix molecules giving secondary products and are uptaken into the negatively charged mitochondrial membranes. Thus, reported compounds feature a rare dissociation-driven mechanism of action with great potential for biological applications. Full article

(This article belongs to the Section Organometallic Chemistry)

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17 pages, 1682 KiB

Open AccessArticle

Using UPLC-MS/MS for Characterization of Active Components in Extracts of Yupingfeng and Application to a Comparative Pharmacokinetic Study in Rat Plasma after Oral Administration

by Meng-Qi Jia^1,†, Ye-Juan Xiong^2,†, Yun Xue¹, Yan Wang^1,*

and Chao Yan¹

¹ School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China

² Shanghai University of Medicine & Health Sciences, Shanghai 201318, China

^† These two authors contributed equally to this work.

Molecules 2017, 22(5), 810; https://doi.org/10.3390/molecules22050810 - 17 May 2017

Cited by 27 | Viewed by 6045

Abstract

Yupingfeng (YPF), a famous traditional Chinese medicine, which contains a large array of compounds, has been effectually used in health protection. A two-dimensional liquid chromatography (²D-LC) combined with quadrupole time-of-flight mass spectrometry (QTOF-MS) method was firstly established to separate and identify [...] Read more.

Yupingfeng (YPF), a famous traditional Chinese medicine, which contains a large array of compounds, has been effectually used in health protection. A two-dimensional liquid chromatography (²D-LC) combined with quadrupole time-of-flight mass spectrometry (QTOF-MS) method was firstly established to separate and identify chemical components in YPF. A total of 33 compounds were identified, including 15 constituents (flavonoids and saponins) in Astragali radix; seven constituents (sesquiterpenoids and polysaccharide) in Atractylodis rhizoma; and 11 constituents (chromone and coumarins) in Saposhnikoviae radix. The corresponding fragmentation pathway of typical substances was investigated. Then, seven active constituents (astragaloside, calycosin, formononetin, cimicifugoside, 4-O-beta-d-glucosyl-5-O-methylvisamminol, sec-O-glucosylhamaudol, and atractylenolide II) derived from three medicinal plants were chosen to further investigate the pharmacokinetic behavior of YPF formula using ultrahigh-performance liquid chromatography with triple quadrupole mass spectrometry system. The method was sensitive, accurate and reliable. We also used the area under the plasma concentration–time curve from zero to infinity (AUC_0−∞) as weighting factor to make an integrated pharmacokinetic curve. Results show that the constituents of Saposhnikoviae radix have the best absorption and pharmacokinetic behavior and may play important role in leading to the changes of overall therapeutic effects of YPF. Further study is needed to confirm the association between them. Full article

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17 pages, 6560 KiB

Open AccessArticle

The Phenolic Fraction of Mentha haplocalyx and Its Constituent Linarin Ameliorate Inflammatory Response through Inactivation of NF-κB and MAPKs in Lipopolysaccharide-Induced RAW264.7 Cells

by Xiangyang Chen¹, Shujing Zhang², Zinan Xuan³, Dongyu Ge², Xiaoming Chen³, Junjie Zhang³, Qian Wang⁴, Ying Wu^3,* and Bin Liu^1,*

¹ Department of Traditional Chinese Medicine Chemistry, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China

² Department of Scientific Research Center, School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China

³ Department of Microbiology and Immunology, School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, China

⁴ Department of Pathology, School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China

Molecules 2017, 22(5), 811; https://doi.org/10.3390/molecules22050811 - 16 May 2017

Cited by 56 | Viewed by 7441

Abstract

Mentha haplocalyx has been widely used for its flavoring and medicinal properties and as a traditional Chinese medicine with its anti-inflammation properties. The present study was designed to investigate the anti-inflammatory effects and potential molecular mechanisms of the phenolic fraction of M. haplocalyx [...] Read more.

Mentha haplocalyx has been widely used for its flavoring and medicinal properties and as a traditional Chinese medicine with its anti-inflammation properties. The present study was designed to investigate the anti-inflammatory effects and potential molecular mechanisms of the phenolic fraction of M. haplocalyx (MHP) and its constituent linarin in lipopolysaccharide (LPS)-induced RAW264.7 cells. The high-performance liquid chromatography coupled with linear ion trap-orbitrap mass spectrometry (HPLC-LTQ-Orbitrap MS) was used to analyze the chemical composition of MHP. Using the enzyme-linked immunosorbent assay (ELISA) and quantitative realtime polymerase chain reaction (qRT-PCR), the expression of pro-inflammatory meditators and cytokines was measured at the transcriptional and translational levels. Western blot analysis was used to further investigate changes in the nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and Akt signaling pathways. Fourteen phenolic constituents were identified from MHP based on the data of the mass spectrometry (MS)/MS analysis. MHP and linarin decreased the production of NO, tumor necrosis factor-α (TNF-α), interlenkin-1β (IL-1β), and IL-6. The messenger ribonucleic acid (mRNA) expression levels of inducible NO synthase (iNOS), TNF-α, IL-1β, and IL-6 were also suppressed by MHP and linarin. Further investigation showed that MHP and linarin down-regulated LPS-induced phosphorylation content of NF-κB p65, inhibitor kappa B α (IκBα), extracellular signal-regulated kinase (ERK), c-Jun NH₂-terminal kinase (JNK), and p38. However, MHP and linarin showed no inhibitory effect on the phosphorylated Akt. These results suggested that MHP and linarin exerted a potent inhibitory effect on pro-inflammatory meditator and cytokines production via the inactivation of NF-κB and MAPKs, and they may serve as potential modulatory agents for the prevention and treatment of inflammatory diseases. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 883 KiB

Open AccessArticle

Evaluation of the Mycobactericidal Effect of Thio-functionalized Carbohydrate Derivatives

by Małgorzata Korycka-Machała¹, Anna Brzostek¹

, Bożena Dziadek², Malwina Kawka², Tomasz Popławski³

, Zbigniew J. Witczak^4,* and Jarosław Dziadek^1,*

¹ Institute of Medical Biology, Polish Academy of Sciences, Lodz 93-232, Poland

² Department of Immunoparasitology, University of Lodz, Lodz 90-236, Poland

³ Department of Molecular Genetics, University of Lodz, Lodz 90-236, Poland

⁴ Department of Pharmaceutical Sciences, Nesbitt School of Pharmacy, Wilkes University, Wilkes-Barre, PA 18766, USA

Molecules 2017, 22(5), 812; https://doi.org/10.3390/molecules22050812 - 16 May 2017

Cited by 21 | Viewed by 5079

Abstract

Sugars with heteroatoms other than oxygen have attained considerable importance in glycobiology and in drug design since they are often more stable in blood plasma due to their resistance to enzymes, such as glycosidases, phosphorylases and glycosyltransferases. The replacement of oxygen atoms in [...] Read more.

Sugars with heteroatoms other than oxygen have attained considerable importance in glycobiology and in drug design since they are often more stable in blood plasma due to their resistance to enzymes, such as glycosidases, phosphorylases and glycosyltransferases. The replacement of oxygen atoms in sugars with sulfur forms thio-sugars, which are potentially useful for the treatment of diabetes and some bacterial and viral infections. Here, we evaluated the antibacterial activity of thio-functionalized carbohydrate derivatives. A set of 21 compounds was screened against acid-fast Mycobacterium tuberculosis (Mtb), gram-negative Escherichia coli and gram-positive Staphylococcus aureus. The tested carbohydrate derivatives were most effective against tubercle bacilli, with as many as five compounds (thioglycoside 6, thiosemicarbazone 16A, thiosemicarbazone 20, aminothiadiazole 23, and thiazoline 26) inhibiting its growth with MIC₅₀ ≤ 50 µM/CFU. Only two compounds (aminothiadiazole 23 and thiazoline 26) were able to inhibit the growth of E. coli at concentrations below 1 mM, and one of them, aminothiadiazole 23, inhibited the growth of S. aureus at a concentration ≤1 mM. The five compounds affecting the growth of mycobacteria were either thiodisaccharides (6, 16A, and 20) or thioglycosides (23 and 26). All of these compounds (6, 16A, 20, 23, and 26) were able to inhibit the growth of Mtb deposited within human macrophages. However, three of the five selected compounds (6, 23, and 26) exhibited relatively high cytotoxicity in mouse fibroblasts at micromolar concentrations. The selected thio-sugars are very promising compounds, thus making them candidates for further modifications that would decrease their cytotoxicity against eukaryotic cells without affecting their antimycobacterial potential. Full article

(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)

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19 pages, 2920 KiB

Open AccessArticle

Optimization of EPS Production and Characterization by a Halophilic Bacterium, Kocuria rosea ZJUQH from Chaka Salt Lake with Response Surface Methodology

by Di Gu¹, Yingchun Jiao², Jianan Wu¹, Zhengjie Liu¹ and Qihe Chen^1,*

¹ Department of Food Science and Nutrition, Zhejiang University, Hangzhou 310058, China

² College of Eco-Environmental Engineering, Qinghai Province, Xining 810016, China

Molecules 2017, 22(5), 814; https://doi.org/10.3390/molecules22050814 - 16 May 2017

Cited by 34 | Viewed by 7111

Abstract

With the rising awareness of microbial exopolysaccharides (EPSs) application in various fields, halophilic microorganisms which produce EPSs have received broad attention. A newly identified Kocuria rosea ZJUQH CCTCC M2016754 was determined to be a moderate halobacterium on account of its successful adaption to [...] Read more.

With the rising awareness of microbial exopolysaccharides (EPSs) application in various fields, halophilic microorganisms which produce EPSs have received broad attention. A newly identified Kocuria rosea ZJUQH CCTCC M2016754 was determined to be a moderate halobacterium on account of its successful adaption to the environment containing 10% NaCl. The optimal combination of fermentation medium compositions on EPS production was studied. In this work, a fractional factorial design was adopted to investigate the significant factors that affected EPS production. The factors of KCl and MgSO₄ were found to have a profound impact on EPS production. We utilized central composite design and response surface methodology to derive a statistical model for optimizing the submerged culture medium composition. Judging from these experimental results, the optimum culture medium for producing EPSs was composed of 0.50% casein hydrolysate, 1.00% sodium citrate, 0.30% yeast extract, 0.50% KCl, 0.50% peptone, and 5.80% MgSO₄ (initial pH 7.0). The maximal EPS was 48.01 g/L, which is close to the predicted value (50.39 g/L). In the validation experiment, the highest concentration of 70.64 g/L EPSs was obtained after 120 h under the optimized culture medium in a 5-L bioreactor. EPS from this bacterium was also characterized by differential scanning calorimetry (DSC) and Fourier transform infrared analysis (FT-IR). The findings in this study imply that Kocuria rosea ZJUQH has great potential to be exploited as a source of EPSs utilized in food, the pharmaceutical and agriculture industry, and in the biotreatment of hypersaline environments. Full article

(This article belongs to the Special Issue Natural Polysaccharides)

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10 pages, 1770 KiB

Open AccessArticle

Leishmanicidal Activity and Structure-Activity Relationships of Essential Oil Constituents

by Audrey R. S. T. Silva¹, Ricardo Scher², Flaviane V. Santos², Sebastião R. Ferreira^3,4, Sócrates C. H. Cavalcanti¹, Cristiane B. Correa², Lilian L. Bueno³, Ricardo J. Alves⁵, Damião P. Souza⁶

, Ricardo T. Fujiwara³ and Silvio S. Dolabella^1,7,*

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

² Laboratory of Molecular Biology of Pathogenic Bioagents, Department of Morphology, Federal University of Sergipe, 49100-000 São Cristóvão, Sergipe, Brazil

³ Department of Parasitology, Biological Sciences Institute, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil

⁴ Health Science Center, Federal University of Roraima, Av. Cap. Ene Garcez, 69310-000 Boa Vista, Roraima, Brazil

⁵ Department of Pharmaceutical Products, Federal University of Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil

⁶ Department of Pharmaceutical Sciences, Federal University of Paraíba, 58051-900 João Pessoa, Paraíba, Brazil

⁷ Laboratory of Parasitology and Tropical Entomology, Department of Morphology, Federal University of Sergipe, 49100-000 São Cristóvão, Sergipe, Brazil

Molecules 2017, 22(5), 815; https://doi.org/10.3390/molecules22050815 - 16 May 2017

Cited by 43 | Viewed by 6128

Abstract

Several constituents of essential oils have been shown to be active against pathogens such as bacteria, fungi, and protozoa. This study demonstrated the in vitro action of ten compounds present in essential oils against Leishmania amazonensis promastigotes. With the exception of p-cymene, [...] Read more.

Several constituents of essential oils have been shown to be active against pathogens such as bacteria, fungi, and protozoa. This study demonstrated the in vitro action of ten compounds present in essential oils against Leishmania amazonensis promastigotes. With the exception of p-cymene, all evaluated compounds presented leishmanicidal activity, exhibiting IC₅₀ between 25.4 and 568.1 μg mL⁻¹. Compounds with the best leishmanicidal activity presented a phenolic moiety (IC₅₀ between 25.4 and 82.9 μg mL⁻¹). Alicyclic alcohols ((−)-menthol and isoborneol) and ketones ((−)-carvone) promoted similar activity against the parasite (IC₅₀ between 190.2 and 198.9 μg mL⁻¹). Most of the compounds showed low cytotoxicity in L929 fibroblasts. Analysis of the structure-activity relationship of these compounds showed the importance of the phenolic structure for the biological action against the promastigote forms of the parasite. Full article

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

12 pages, 1065 KiB

Open AccessArticle

Cation, Anion and Ion-Pair Complexes with a G-3 Poly(ethylene imine) Dendrimer in Aqueous Solution

by Matteo Savastano¹

, Carla Bazzicalupi¹

, Claudia Giorgi¹, Paola Gratteri²

and Antonio Bianchi^1,*

¹ Department of Chemistry “Ugo Schiff”, via della Lastruccia 3, 50019 Sesto Fiorentino, Italy

² NEUROFARBA Department, Pharmaceutical and Nutraceutical Section, and Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy

Molecules 2017, 22(5), 816; https://doi.org/10.3390/molecules22050816 - 16 May 2017

Cited by 5 | Viewed by 5148

Abstract

The G-3 poly(ethylene imine) ligand L2 shows a multifaceted coordination ability, being able to bind metal cations, anions and ion-pairs. The equilibrium constants for the formation of metal (Cu²⁺, Zn²⁺), anion (SO₄²⁻) and ion-pair (Cu²⁺ [...] Read more.

The G-3 poly(ethylene imine) ligand L2 shows a multifaceted coordination ability, being able to bind metal cations, anions and ion-pairs. The equilibrium constants for the formation of metal (Cu²⁺, Zn²⁺), anion (SO₄²⁻) and ion-pair (Cu²⁺/SO₄²⁻) complexes were determined in 0.1 M Me₄NCl aqueous solution at 298.1 ± 0.1 K by means of potentiometric titrations. Thanks to its dendrimeric nature, L2 can form highly nucleated metal complexes, such as Cu₅L2¹⁰⁺ and Zn₄L2⁸⁺, in successive and well-defined complexation steps. Protonated forms of L2 give rise to relatively weak anion complexes with SO₄²⁻, but the addition of Cu²⁺ significantly enhances the binding ability of the ligand toward this anion below pH 9. In more alkaline solutions, an opposite trend is observed. The coordination properties of L2 are discussed with the support of modelling calculations. According to results, L2 is a promising molecule for the preparation of solid supported materials for the recovery of cations and anions from aqueous media and/or for applications in heterogeneous catalysis. Full article

(This article belongs to the Special Issue Dendrimers: A Themed Issue in Honor of Professor Donald A. Tomalia on the Occasion of His 80th Birthday)

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13 pages, 20472 KiB

Open AccessArticle

Synthesis of Pyrimethanil-Loaded Mesoporous Silica Nanoparticles and Its Distribution and Dissipation in Cucumber Plants

by Pengyue Zhao¹

, Lidong Cao¹

, Dukang Ma¹, Zhaolu Zhou¹, Qiliang Huang^1,* and Canping Pan^2,*

¹ Key Laboratory of Integrated Pest Management in Crops, Ministry of Agriculture, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, No. 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, China

² Department of Applied Chemistry, College of Science, China Agricultural University, No. 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, China

Molecules 2017, 22(5), 817; https://doi.org/10.3390/molecules22050817 - 16 May 2017

Cited by 44 | Viewed by 7714

Abstract

Mesoporous silica nanoparticles are used as pesticide carries in plants, which has been considered as a novel method to reduce the indiscriminate use of conventional pesticides. In the present work, mesoporous silica nanoparticles with particle diameters of 200–300 nm were synthesized in order [...] Read more.

Mesoporous silica nanoparticles are used as pesticide carries in plants, which has been considered as a novel method to reduce the indiscriminate use of conventional pesticides. In the present work, mesoporous silica nanoparticles with particle diameters of 200–300 nm were synthesized in order to obtain pyrimethanil-loaded nanoparticles. The microstructure of the nanoparticles was observed by scanning electron microscopy. The loading content of pyrimethanil-loaded nanoparticles was investigated. After treatment on cucumber leaves, the concentrations of pyrimethanil were determined in different parts of cucumber over a period of 48 days using high performance liquid chromatography tandem mass spectrometry. It was shown that the pyrimethanil-loaded mesoporous silica nanoparticles might be more conducive to acropetal, rather than basipetal, uptake, and the dosage had almost no effect on the distribution and dissipation rate in cucumber plants. The application of the pesticide-loaded nanoparticles in leaves had a low risk of pyrimethanil accumulating in the edible part of the plant. Full article

(This article belongs to the Special Issue Mesoporous Silica in Biomedical Applications)

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12 pages, 4232 KiB

Open AccessArticle

Supporting the Identification of Novel Fragment-Based Positive Allosteric Modulators Using a Supervised Molecular Dynamics Approach: A Retrospective Analysis Considering the Human A2A Adenosine Receptor as a Key Example

by Giuseppe Deganutti and Stefano Moro^*

Molecular Modeling Section (MMS), Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padua, Italy

Molecules 2017, 22(5), 818; https://doi.org/10.3390/molecules22050818 - 16 May 2017

Cited by 17 | Viewed by 5544

Abstract

Structure-driven fragment-based (SDFB) approaches have provided efficient methods for the identification of novel drug candidates. This strategy has been largely applied in discovering several pharmacological ligand classes, including enzyme inhibitors, receptor antagonists and, more recently, also allosteric (positive and negative) modulators. Recently, Siegal [...] Read more.

Structure-driven fragment-based (SDFB) approaches have provided efficient methods for the identification of novel drug candidates. This strategy has been largely applied in discovering several pharmacological ligand classes, including enzyme inhibitors, receptor antagonists and, more recently, also allosteric (positive and negative) modulators. Recently, Siegal and collaborators reported an interesting study, performed on a detergent-solubilized StaR adenosine A_2A receptor, describing the existence of both fragment-like negative allosteric modulators (NAMs), and fragment-like positive allosteric modulators (PAMs). From this retrospective study, our results suggest that Supervised Molecular Dynamics (SuMD) simulations can support, on a reasonable time scale, the identification of fragment-like PAMs following their receptor recognition pathways and characterizing the possible allosteric binding sites. Full article

(This article belongs to the Special Issue Adenosine Receptors)

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12 pages, 1813 KiB

Open AccessArticle

Biomimetic Synthesis of Resveratrol Trimers Catalyzed by Horseradish Peroxidase

by Jian-Qiao Zhang¹, Gan-Peng Li², Yu-Long Kang¹, Bin-Hao Teng¹ and Chun-Suo Yao^1,*

¹ State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

² Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University, Kunming 650500, China

Molecules 2017, 22(5), 819; https://doi.org/10.3390/molecules22050819 - 17 May 2017

Cited by 16 | Viewed by 5140

Abstract

Biotransformation of trans-resveratrol and synthetic (±)-ε-viniferin in aqueous acetone using horseradish peroxidase and hydrogen peroxide as oxidants resulted in the isolation of two new resveratrol trimers (3 and 4), one new resveratrol derivative (5) with a dihydrobenzofuran skeleton, [...] Read more.

Biotransformation of trans-resveratrol and synthetic (±)-ε-viniferin in aqueous acetone using horseradish peroxidase and hydrogen peroxide as oxidants resulted in the isolation of two new resveratrol trimers (3 and 4), one new resveratrol derivative (5) with a dihydrobenzofuran skeleton, together with two known stilbene trimers (6 and 7), and six known stilbene dimers (8–13). Their structures and relative configurations were identified through spectral analysis and possible formation mechanisms were also discussed. Among these oligomers, trimers 6 and 7 were obtained for the first time through direct transformation from resveratrol. Results indicated that this reaction is suitable for the preparation of resveratrol oligomers with a complex structure. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 1221 KiB

Open AccessArticle

One-Flask Synthesis of Pyrazolo[3,4-d]pyrimidines from 5-Aminopyrazoles and Mechanistic Study

by Wan-Ping Yen^1,2, Shuo-En Tsai^1,2, Naoto Uramaru³, Hiroyuki Takayama⁴ and Fung Fuh Wong^1,*

¹ School of Pharmacy, China Medical University, No. 91 Hsueh-Shih Rd., Taichung 40402, Taiwan

² Program for Biotech Pharmaceutical Industry, China Medical University, No. 91 Hsueh-Shih Rd., Taichung 40402, Taiwan

³ Department of Environmental Science, Nihon Pharmaceutical University, Komuro Inamachi Kita-adachi-gun, Saitama-ken 10281, Japan

⁴ Department of Medico Pharmaceutical Science, Nihon Pharmaceutical University, Komuro Inamachi Kita-adachi-gun, Saitama-ken 10281, Japan

Molecules 2017, 22(5), 820; https://doi.org/10.3390/molecules22050820 - 16 May 2017

Cited by 7 | Viewed by 5604

Abstract

A novel one-flask synthetic method was developed in which 5-aminopyrazoles were reacted with N,N-substituted amides in the presence of PBr₃. Hexamethyldisilazane was then added to perform heterocyclization to produce the corresponding pyrazolo[3,4-d]pyrimidines in suitable yields. These one-flask reactions [...] Read more.

A novel one-flask synthetic method was developed in which 5-aminopyrazoles were reacted with N,N-substituted amides in the presence of PBr₃. Hexamethyldisilazane was then added to perform heterocyclization to produce the corresponding pyrazolo[3,4-d]pyrimidines in suitable yields. These one-flask reactions thus involved Vilsmeier amidination, imination reactions, and the sequential intermolecular heterocyclization. To study the reaction mechanism, a series of 4-formyl-1,3-diphenyl-1H-pyrazol-5-yl-N,N-disubstituted formamidines, which were conceived as the chemical equivalent of 4-(iminomethyl)-1,3-diphenyl-1H-pyrazol-5-yl-formamidine, were prepared and successfully converted into pyrazolo[3,4-d]pyrimidines. The experiments demonstrated that the reaction intermediates were the chemical equivalents of 4-(iminomethyl)-1,3-diphenyl-1H-pyrazol-5-yl)formamidines. The rate of the reaction could be described as being proportional to the reactivity of amine reactants during intermolecular heterocyclization, especially when hexamethyldisilazane was used. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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11 pages, 1633 KiB

Open AccessArticle

From Cell to Beak: In-Vitro and In-Vivo Characterization of Chicken Bitter Taste Thresholds

by Shira Cheled-Shoval^1,2, Maik Behrens³, Ayelet Korb¹, Antonella Di Pizio², Wolfgang Meyerhof³, Zehava Uni¹ and Masha Y. Niv^2,*

¹ Department of Animal Science, The Robert H. Smith Faculty of Agriculture, Food, and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel

² The Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food, and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel

³ Department of Molecular Genetics, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany

Molecules 2017, 22(5), 821; https://doi.org/10.3390/molecules22050821 - 17 May 2017

Cited by 20 | Viewed by 6283

Abstract

Bitter taste elicits an aversive reaction, and is believed to protect against consuming poisons. Bitter molecules are detected by the Tas2r family of G-protein-coupled receptors, with a species-dependent number of subtypes. Chickens demonstrate bitter taste sensitivity despite having only three bitter taste receptors—ggTas2r1, [...] Read more.

Bitter taste elicits an aversive reaction, and is believed to protect against consuming poisons. Bitter molecules are detected by the Tas2r family of G-protein-coupled receptors, with a species-dependent number of subtypes. Chickens demonstrate bitter taste sensitivity despite having only three bitter taste receptors—ggTas2r1, ggTas2r2 and ggTas2r7. This minimalistic bitter taste system in chickens was used to determine relationships between in-vitro (measured in heterologous systems) and in-vivo (behavioral) detection thresholds. ggTas2r-selective ligands, nicotine (ggTas2r1), caffeine (ggTas2r2), erythromycin and (+)-catechin (ggTas2r7), and the Tas2r-promiscuous ligand quinine (all three ggTas2rs) were studied. Ligands of the same receptor had different in-vivo:in-vitro ratios, and the ggTas2r-promiscuous ligand did not exhibit lower in-vivo:in-vitro ratios than ggTas2r-selective ligands. In-vivo thresholds were similar or up to two orders of magnitude higher than the in-vitro ones. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 2691 KiB

Open AccessArticle

Antibacterial Activity of 7-Epiclusianone and Its Novel Copper Metal Complex on Streptococcus spp. Isolated from Bovine Mastitis and Their Cytotoxicity in MAC-T Cells

by Mariana De Barros¹, Pedro Griffo Perciano^†, Marcelo Henrique Dos Santos², Leandro Licursi De Oliveira³

, Éderson D’Martin Costa⁴

and Maria Aparecida Scatamburlo Moreira^1,*

¹ Department of Veterinary, Universidade Federal de Viçosa, Viçosa 36570-900, Brazil

² Department of Chemistry, Universidade Federal de Viçosa, Viçosa 36570-900, Brazil

³ Department of General Biology, Universidade Federal de Viçosa, Viçosa 36570-900, Brazil

⁴ Institute of Chemistry, Universidade Federal de Alfenas, Alfenas 37130-000, Brazil

^† Deceased.

Molecules 2017, 22(5), 823; https://doi.org/10.3390/molecules22050823 - 17 May 2017

Cited by 16 | Viewed by 5113

Abstract

Mastitis is an inflammation of mammary gland parenchyma that adversely affects bovine health and dairy production worldwide despite significant efforts to eradicate it. The aim of this work was to characterize the antimicrobial activity of 7-epiclusianone (7-epi), a compound extracted from the Rheedia [...] Read more.

Mastitis is an inflammation of mammary gland parenchyma that adversely affects bovine health and dairy production worldwide despite significant efforts to eradicate it. The aim of this work was to characterize the antimicrobial activity of 7-epiclusianone (7-epi), a compound extracted from the Rheedia brasiliensis fruit, its complex with copper against Streptococcus spp. isolated from bovine mastitis, and to assess their cytotoxicity to bovine mammary alveolar cells (MAC-T). The complex 7-epiclusianone-Cu (7-epi-Cu) was an amorphous green solid with optical activity. Its vibrational spectrum in the infrared region showed absorption bands in the high-frequency region, as well as bands that can be attributed to the unconjugated and conjugated stretching of the free ligand. The complex was anhydrous. One of the tested bacterial strains was not sensitive to the compounds, while the other three had MIC values of 7.8 µg mL⁻¹ and minimum bactericidal concentration (MBC) values between 15.6 and 31.3 µg mL⁻¹. These two compounds are bacteriostatic, did not cause damage to the cell wall and, at sub-inhibitory concentrations, did not induce bacterial adhesion. The compounds were not cytotoxic. Based on these results, 7-epi and 7-epi-Cu exhibited desirable antimicrobial properties and could potentially be used in bovine mastitis treatment. Full article

(This article belongs to the Section Medicinal Chemistry)

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22 pages, 11114 KiB

Open AccessArticle

Effects of Growth Media on the Diversity of Culturable Fungi from Lichens

by Lucia Muggia^1,*,†

, Theodora Kopun^2,† and Martin Grube²

¹ Department of Life Sciences, University of Trieste, via Giorgieri 10, 34127 Trieste, Italy

² Institute of Plant Science, Karl-Franzens University of Graz, Holteigasse 6, 8010 Graz, Austria

^† These authors contributed equally to the work.

Molecules 2017, 22(5), 824; https://doi.org/10.3390/molecules22050824 - 17 May 2017

Cited by 60 | Viewed by 11498

Abstract

Microscopic and molecular studies suggest that lichen symbioses contain a plethora of associated fungi. These are potential producers of novel bioactive compounds, but strains isolated on standard media usually represent only a minor subset of these fungi. By using various in vitro growth [...] Read more.

Microscopic and molecular studies suggest that lichen symbioses contain a plethora of associated fungi. These are potential producers of novel bioactive compounds, but strains isolated on standard media usually represent only a minor subset of these fungi. By using various in vitro growth conditions we are able to modulate and extend the fraction of culturable lichen-associated fungi. We observed that the presence of iron, glucose, magnesium and potassium in growth media is essential for the successful isolation of members from different taxonomic groups. According to sequence data, most isolates besides the lichen mycobionts belong to the classes Dothideomycetes and Eurotiomycetes. With our approach we can further explore the hidden fungal diversity in lichens to assist in the search of novel compounds. Full article

(This article belongs to the Special Issue Lichens: Chemistry, Ecological and Biological Activities)

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12 pages, 2767 KiB

Open AccessArticle

Detecting and Discriminating Shigella sonnei Using an Aptamer-Based Fluorescent Biosensor Platform

by Myeong-Sub Song^1,†, Simranjeet Singh Sekhon^1,†, Woo-Ri Shin^1,†, Hyung Cheol Kim², Jiho Min³, Ji-Young Ahn^1,* and Yang-Hoon Kim^1,*

¹ School of Biological Sciences, Chungbuk National University, 1 Chungdae-Ro, Seowon-Gu, Cheongju 28644, Korea

² Technology Transfer Center, Korea Research Institute of Bioscience & Biotechnology, 125 Gwahak-Ro, Yuseong-Gu, Daejeon 34141, Korea

³ Department of Bioprocess Engineering, Chonbuk National University, 567 Baekje-daero, Deokjin-Gu Jeonju, Jeonbuk 54896, Korea

^† These authors contributed equally to this work.

Molecules 2017, 22(5), 825; https://doi.org/10.3390/molecules22050825 - 17 May 2017

Cited by 82 | Viewed by 8218

Abstract

In this paper, a Whole-Bacteria SELEX (WB-SELEX) strategy was adopted to isolate specific aptamers against Shigella sonnei. Real-time PCR amplification and post-SELEX experiment revealed that the selected aptmers possessed a high binding affinity and specificity for S. sonnei. Of the 21 [...] Read more.

In this paper, a Whole-Bacteria SELEX (WB-SELEX) strategy was adopted to isolate specific aptamers against Shigella sonnei. Real-time PCR amplification and post-SELEX experiment revealed that the selected aptmers possessed a high binding affinity and specificity for S. sonnei. Of the 21 aptamers tested, the C(t) values of the SS-3 and SS-4 aptamers (Ct = 13.89 and Ct = 12.23, respectively) had the lowest value compared to other aptamer candidates. The SS-3 and SS-4 aptamers also displayed a binding affinity (K_D) of 39.32 ± 5.02 nM and 15.89 ± 1.77 nM, respectively. An aptamer-based fluorescent biosensor assay was designed to detect and discriminate S. sonnei cells using a sandwich complex pair of SS-3 and SS-4. The detection of S. sonnei by the aptamer based fluorescent biosensor platform consisted of three elements: (1) 5’amine-SS-4 modification in a 96-well type microtiter plate surface (N-oxysuccinimide, NOS) as capture probes; (2) the incubation with S. sonnei and test microbes in functionalized 96 assay wells in parallel; (3) the readout of fluorescent activity using a Cy5-labeled SS-3 aptamer as the detector. Our platform showed a significant ability to detect and discriminate S. sonnei from other enteric species such as E. coli, Salmonella typhimurium and other Shigella species (S. flexneri, S. boydii). In this study, we demonstrated the feasibility of an aptamer sensor platform to detect S. sonnei in a variety of foods and pave the way for its use in diagnosing shigellosis through multiple, portable designs. Full article

(This article belongs to the Special Issue Synthesis and Applications of Oligonucleotide Conjugates)

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12 pages, 2627 KiB

Open AccessArticle

Highly Stereoselective Synthesis of a Compound Collection Based on the Bicyclic Scaffolds of Natural Products

by Murali Annamalai¹, Stanimira Hristeva², Martyna Bielska², Raquel Ortega² and Kamal Kumar^1,*

¹ Max-Planck-Institut für molekulare Physiologie, Otto-Hahn-Straße 11, 44227 Dortmund, Germany

² Medicinal Chemistry, Taros Chemicals GmbH & Co. KG, Emil Figge-Str. 76a, 44227 Dortmund, Germany

Molecules 2017, 22(5), 827; https://doi.org/10.3390/molecules22050827 - 18 May 2017

Cited by 11 | Viewed by 9157

Abstract

Despite the great contribution of natural products in the history of successful drug discovery, there are significant limitations that persuade the pharmaceutical industry to evade natural products in drug discovery research. The extreme scarcity as well as structural complexity of natural products renders [...] Read more.

Despite the great contribution of natural products in the history of successful drug discovery, there are significant limitations that persuade the pharmaceutical industry to evade natural products in drug discovery research. The extreme scarcity as well as structural complexity of natural products renders their practical synthetic access and further modifications extremely challenging. Although other alternative technologies, particularly combinatorial chemistry, were embraced by the pharmaceutical industry to get quick access to a large number of small molecules with simple frameworks that often lack three-dimensional complexity, hardly any success was achieved in the discovery of lead molecules. To acquire chemotypes beholding structural features of natural products, for instance high sp³ character, the synthesis of compound collections based on core-scaffolds of natural products presents a promising strategy. Here, we report a natural product inspired synthesis of six different chemotypes and their derivatives for drug discovery research. These bicyclic hetero- and carbocyclic scaffolds are highly novel, rich in sp³ features and with ideal physicochemical properties to display drug likeness. The functional groups on the scaffolds were exploited further to generate corresponding compound collections. Synthesis of two of these collections exemplified with ca. 350 compounds are each also presented. The whole compound library is being exposed to various biological screenings within the European Lead Factory consortium. Full article

(This article belongs to the Special Issue Natural Product Inspired Scaffolds Designs)

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8 pages, 621 KiB

Open AccessArticle

New Glycosides from the Fruits of Nicandra physaloides

by Yan Liu, Hai-Bing Jiang, Zhen-Peng Xu, Yan-Gang Cheng, Shao-Wa Lv, Bing-You Yang, Hong-Wei Guo^* and Hai-Xue Kuang^*

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

Molecules 2017, 22(5), 828; https://doi.org/10.3390/molecules22050828 - 17 May 2017

Cited by 15 | Viewed by 6047

Abstract

Three new glycosides (1–3) and 15 known ones (4–18) were isolated and identified from the fruits of Nicandra physaloides. The structures of these compounds were established by 1D and 2D NMR spectra and HR-ESI-MS. [...] Read more.

Three new glycosides (1–3) and 15 known ones (4–18) were isolated and identified from the fruits of Nicandra physaloides. The structures of these compounds were established by 1D and 2D NMR spectra and HR-ESI-MS. The compounds (4–18) were the first time isolated from the Nicandra genus and they (except 8, 10, 14) exhibited inhibitions on the NO release of LPS-induced RAW 264.7 cells with IC₅₀ values from 26.9 to 47.5 μM. Full article

(This article belongs to the Collection Bioactive Compounds)

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11 pages, 2350 KiB

Open AccessArticle

Microwave-Assisted Synthesis of Imidazo[4,5-f][1,10]phenanthroline Derivatives as Apoptosis Inducers in Chemotherapy by Stabilizing Bcl-2 G-quadruplex DNA

by Li Li^1,2,†, Jie-Qiong Cao^3,†, Hui-Min Liu¹, Qiong Wu³, Qiu-Hui Pan^4,*, Zhi-Ping Zeng², Yu-Tao Lan⁵, Yu-Mei Li², Wen-Jie Mei^2,*, Xi-Cheng Wang^1,* and Wen-Jie Zheng³

¹ The First Affiliation Hospital, Guangdong Pharmaceutical University, Guangzhou 510006, China

² School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China

³ Department of Chemistry, Jinan University, Guangzhou 510006, China

⁴ Department of Laboratory Medicine, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China

⁵ School of Nursing, Guangdong Pharmaceutical University, Guangzhou 510006, China

^† These authors contributed equally to this work.

Molecules 2017, 22(5), 829; https://doi.org/10.3390/molecules22050829 - 20 May 2017

Cited by 9 | Viewed by 6086

Abstract

Herein, a series of imidazo[4,5-f][1,10] phenanthroline derivatives RPIP (PIP = imidazo [4,5-f][1,10] phenanthroline, R = NO₂, 1; CF₃, 2; Cl, 3; OH, 4) have been synthesized in yields of 82.3–94.7% at [...] Read more.

Herein, a series of imidazo[4,5-f][1,10] phenanthroline derivatives RPIP (PIP = imidazo [4,5-f][1,10] phenanthroline, R = NO₂, 1; CF₃, 2; Cl, 3; OH, 4) have been synthesized in yields of 82.3–94.7% at 100 °C under the irradiation of microwave. MTT assay has been utilized to evaluate the inhibitory activity (IC₅₀) of these compounds against the growth of various tumor cells, and the results revealed that these compounds, especially 1, exhibited excellent inhibitory activity against the growth of A549 cells with IC₅₀ of 15.03 μM. Moreover, it’s also confirmed that 1 can penetrate into the membrane of tumor cells and distribute in mitochondria when observed under microscopy, resulting apoptosis of tumor cells. The further studies showed that 1 can bind to bcl-2 G-quadruplex DNA, which demonstrated by the increase of melting point of bcl-2 G4 DNA in the presence of 1, as well as electronic titration and emission spectra. In a word, this kind of compound may develop as a potential apoptosis inducer in cancer chemotherapy via binding and stabilizing to the bcl-2 G-quadruplex DNA. Full article

(This article belongs to the Special Issue ECSOC-20)

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15 pages, 3571 KiB

Open AccessArticle

Protective Effects of Tormentic Acid, a Major Component of Suspension Cultures of Eriobotrya japonica Cells, on Acetaminophen-Induced Hepatotoxicity in Mice

by Wen-Ping Jiang¹, Shyh-Shyun Huang¹, Yoshikazu Matsuda², Hiroshi Saito², Naoto Uramaru², Hui-Ya Ho³, Jin-Bin Wu^1,* and Guan-Jhong Huang^4,*

¹ School of Pharmacy, China Medical University, No. 91, Hsueh-Shih R., Taichung 40402, Taiwan

² Nihon Pharmaceutical University, 10281, Komuro, Ina-machi, Kitaadachi-gun, Saitama 3620806, Japan

³ Jen Li Biotech Company Ltd., Taiping District, Taichung 41143, Taiwan

⁴ Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan

Molecules 2017, 22(5), 830; https://doi.org/10.3390/molecules22050830 - 18 May 2017

Cited by 43 | Viewed by 7568

Abstract

An acetaminophen (APAP) overdose can cause hepatotoxicity and lead to fatal liver damage. The hepatoprotective effects of tormentic acid (TA) on acetaminophen (APAP)-induced liver damage were investigated in mice. TA was intraperitoneally (i.p.) administered for six days prior to APAP administration. Pretreatment with [...] Read more.

An acetaminophen (APAP) overdose can cause hepatotoxicity and lead to fatal liver damage. The hepatoprotective effects of tormentic acid (TA) on acetaminophen (APAP)-induced liver damage were investigated in mice. TA was intraperitoneally (i.p.) administered for six days prior to APAP administration. Pretreatment with TA prevented the elevation of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-Bil), total cholesterol (TC), triacylglycerol (TG), and liver lipid peroxide levels in APAP-treated mice and markedly reduced APAP-induced histological alterations in liver tissues. Additionally, TA attenuated the APAP-induced production of nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and IL-6. Furthermore, the Western blot analysis showed that TA blocked the protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as the inhibition of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) activation in APAP-injured liver tissues. TA also retained the superoxidase dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in the liver. These results suggest that the hepatoprotective effects of TA may be related to its anti-inflammatory effect by decreasing thiobarbituric acid reactive substances (TBARS), iNOS, COX-2, TNF-α, IL-1β, and IL-6, and inhibiting NF-κB and MAPK activation. Antioxidative properties were also observed, as shown by heme oxygenase-1 (HO-1) induction in the liver, and decreases in lipid peroxides and ROS. Therefore, TA may be a potential therapeutic candidate for the prevention of APAP-induced liver injury by inhibiting oxidative stress and inflammation. Full article

(This article belongs to the Section Natural Products Chemistry)

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0 pages, 15378 KiB

Open AccessArticle

In Vitro Assessment of Early Bacterial Activity on Micro/Nanostructured Ti6Al4V Surfaces

by Benjamin Valdez-Salas^1,*,†

, Ernesto Beltrán-Partida^1,2,†

, Sandra Castillo-Uribe¹, Mario Curiel-Álvarez¹, Roumen Zlatev¹

, Margarita Stoytcheva¹

, Gisela Montero-Alpírez¹

and Lidia Vargas-Osuna³

¹ Instituto de Ingeniería, Departamento de Corrosión y Materiales, Universidad Autónoma de Baja California, Blvd. Benito Juárez y Calle de la Normal s/n, Mexicali C.P., 21040 Baja California, Mexico

² Facultad de Odontología Mexicali, Universidad Autónoma de Baja California, Av. Zotoluca y Chinampas, s/n, Mexicali C.P., 21280 Baja California, Mexico

³ Facultad de Ingeniería, Universidad Autónoma de Baja California, Blvd. Benito Juárez y Calle de la Normal s/n, Mexicali C.P., 21040 Baja California, Mexico

^† These authors contributed equally and are considered as co-first authors.

Molecules 2017, 22(5), 832; https://doi.org/10.3390/molecules22050832 - 18 May 2017

Cited by 17 | Viewed by 5910

Abstract

It is imperative to understand and systematically compare the initial interactions between bacteria genre and surface properties. Thus, we fabricated a flat, anodized with 80 nm TiO₂ nanotubes (NTs), and a rough Ti6Al4V surface. The materials were characterized using field-emission scanning electron [...] Read more.

It is imperative to understand and systematically compare the initial interactions between bacteria genre and surface properties. Thus, we fabricated a flat, anodized with 80 nm TiO₂ nanotubes (NTs), and a rough Ti6Al4V surface. The materials were characterized using field-emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX) and atomic force microscopy (AFM). We cultured in vitro Staphylococcus epidermidis (S. epidermidis) and Pseudomonas aeruginosa (P. aeruginosa) to evaluate the bacterial-surface behavior by FE-SEM and viability calculation. In addition, the initial effects of human osteoblasts were tested on the materials. Gram-negative bacteria showed promoted adherence and viability over the flat and rough surface, while NTs displayed opposite activity with altered morphology. Gram-positive bacteria illustrated similar cellular architecture over the surfaces but with promoted surface adhesion bonds on the flat alloy. Rough surfaces supported S. epidermidis viability, whilst NTs exhibited lower vitality. NTs advocated promoted better osteoblast organization with enhanced vitality. Gram-positive bacteria suggested preferred adhesion capability over flat and carbon-rich surfaces. Gram-negative bacteria were strongly disturbed by NTs but largely stimulated by flat and rough materials. Our work proposed that the chemical profile of the material surface and the bacterial cell wall characteristics might play an important role in the bacteria-surface interactions. Full article

(This article belongs to the Special Issue Antibacterial Materials and Coatings)

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8 pages, 1497 KiB

Open AccessArticle

Electrophilic Trifluoromethylselenolation of Boronic Acids

by Clément Ghiazza¹, Anis Tlili¹ and Thierry Billard^1,2,*

¹ Institute of Chemistry and Biochemistry (ICBMS-UMR CNRS 5246), Université de Lyon, Université Lyon 1, CNRS, F-69622 Lyon, France

² CERMEP—In Vivo Imaging, Groupement Hospitalier Est, F-69677 Lyon, France

Molecules 2017, 22(5), 833; https://doi.org/10.3390/molecules22050833 - 19 May 2017

Cited by 28 | Viewed by 8002

Abstract

Trifluoromethylselenylated compounds are emergent compounds with interesting physicochemical properties that still suffer from a lack of efficient synthetic methods. We recently developed an efficient one-pot strategy to generate in situ CF₃SeCl and use it in various reactions. Herein, we continue our [...] Read more.

Trifluoromethylselenylated compounds are emergent compounds with interesting physicochemical properties that still suffer from a lack of efficient synthetic methods. We recently developed an efficient one-pot strategy to generate in situ CF₃SeCl and use it in various reactions. Herein, we continue our study of the reactivity scope of this preformed reagent. Cross-coupling reactions with aromatic and heteroaromatic boronic acids have been investigated. The expected products have been obtained, using a stoichiometric amount of copper, with moderate yields. Full article

(This article belongs to the Special Issue Tri- and Di-Fluoromethylation and Tri- and Di-Fluoromethylchalcogenation Reactions)

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8 pages, 381 KiB

Open AccessArticle

Emulsion-Based Intradermal Delivery of Melittin in Rats

by Sang Mi Han^1,*, Se Gun Kim¹ and Sok Cheon Pak²

¹ Rural Development Administration, National Academy of Agricultural Science, Wanju, Chonbuk 55365, Korea

² School of Biomedical Sciences, Charles Sturt University, Bathurst, NSW 2795, Australia

Molecules 2017, 22(5), 836; https://doi.org/10.3390/molecules22050836 - 19 May 2017

Cited by 5 | Viewed by 5011

Abstract

Bee venom (BV) has long been used as a traditional medicine. The aim of the present study was to formulate a BV emulsion with good rheological properties for dermal application and investigate the effect of formulation on the permeation of melittin through dermatomed [...] Read more.

Bee venom (BV) has long been used as a traditional medicine. The aim of the present study was to formulate a BV emulsion with good rheological properties for dermal application and investigate the effect of formulation on the permeation of melittin through dermatomed rat skin. A formulated emulsion containing 1% (w/v) BV was prepared. The emulsion was compared with distilled water (DW) and 25% (w/v) N-methyl-2-pyrrolidone (NMP) in DW. Permeation of melittin from aqueous solution through the dermatomed murine skin was evaluated using the Franz diffusion cells. Samples of receptor cells withdrawn at pre-determined time intervals were measured for melittin amount. After the permeation study, the same skin was used for melittin extraction. In addition, a known amount of melittin (5 μg/mL) was added to stratum corneum, epidermis, and dermis of the rat skin, and the amount of melittin was measured at pre-determined time points. The measurement of melittin from all samples was done with HPLC-MS/MS. No melittin was detected in the receptor phase at all time points in emulsion, DW, or NMP groups. When the amount of melittin was further analyzed in stratum corneum, epidermis, and dermis from the permeation study, melittin was still not detected. In an additional experiment, the amount of melittin added to all skin matrices was corrected against the amount of melittin recovered. While the total amount of melittin was retained in the stratum corneum, less than 10% of melittin remained in epidermis and dermis within 15 and 30 min, respectively. Skin microporation with BV emulsion facilitates the penetration of melittin across the stratum corneum into epidermis and dermis, where emulsified melittin could have been metabolized by locally-occurring enzymes. Full article

(This article belongs to the Special Issue Bioactive Natural Peptides As A Pipeline For Therapeutics)

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17 pages, 963 KiB

Open AccessArticle

Methodical Challenges and a Possible Resolution in the Assessment of Receptor Reserve for Adenosine, an Agonist with Short Half-Life

by Judit Zsuga¹, Tamas Erdei², Katalin Szabó², Nora Lampe², Csaba Papp¹, Akos Pinter³, Andras Jozsef Szentmiklosi², Bela Juhasz², Zoltán Szilvássy² and Rudolf Gesztelyi^2,*

¹ Department of Health Systems Management and Quality Management for Health Care, Faculty of Public Health, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary

² Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary

³ Institute of Mathematics, Faculty of Science and Technology, University of Debrecen, Egyetem ter 1, H-4032 Debrecen, Hungary

Molecules 2017, 22(5), 839; https://doi.org/10.3390/molecules22050839 - 19 May 2017

Cited by 16 | Viewed by 5903

Abstract

The term receptor reserve, first introduced and used in the traditional receptor theory, is an integrative measure of response-inducing ability of the interaction between an agonist and a receptor system (consisting of a receptor and its downstream signaling). The underlying phenomenon, i.e., stimulation [...] Read more.

The term receptor reserve, first introduced and used in the traditional receptor theory, is an integrative measure of response-inducing ability of the interaction between an agonist and a receptor system (consisting of a receptor and its downstream signaling). The underlying phenomenon, i.e., stimulation of a submaximal fraction of receptors can apparently elicit the maximal effect (in certain cases), provides an opportunity to assess the receptor reserve. However, determining receptor reserve is challenging for agonists with short half-lives, such as adenosine. Although adenosine metabolism can be inhibited several ways (in order to prevent the rapid elimination of adenosine administered to construct concentration–effect (E/c) curves for the determination), the consequent accumulation of endogenous adenosine biases the results. To address this problem, we previously proposed a method, by means of which this bias can be mathematically corrected (utilizing a traditional receptor theory-independent approach). In the present investigation, we have offered in silico validation of this method by simulating E/c curves with the use of the operational model of agonism and then by evaluating them using our method. We have found that our method is suitable to reliably assess the receptor reserve for adenosine in our recently published experimental setting, suggesting that it may be capable for a qualitative determination of receptor reserve for rapidly eliminating agonists in general. In addition, we have disclosed a possible interference between FSCPX (8-cyclopentyl-N³-[3-(4-(fluorosulfonyl)benzoyloxy)propyl]-N¹-propylxanthine), an irreversible A₁ adenosine receptor antagonist, and NBTI (S-(2-hydroxy-5-nitrobenzyl)-6-thioinosine), a nucleoside transport inhibitor, i.e., FSCPX may blunt the effect of NBTI. Full article

(This article belongs to the Special Issue Adenosine Receptors)

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13 pages, 2453 KiB

Open AccessArticle

Exploring the Pivotal Role of the CK2 Hinge Region Sub-Pocket in Binding with Tricyclic Quinolone Analogues by Computational Analysis

by Yue Zhou¹, Na Zhang^2,*, Shan Tang², Xiaoqian Qi², Lijiao Zhao²

, Rugang Zhong² and Yongzhen Peng^1,*

¹ National Engineering Laboratory for Advanced Municipal Wastewater Treatment and Reuse Technology, Engineering Research Center of Beijing, Beijing University of Technology, Beijing 100124, China

² Beijing Key Laboratory of Environmental & Viral Oncology, College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China

Molecules 2017, 22(5), 840; https://doi.org/10.3390/molecules22050840 - 19 May 2017

Cited by 5 | Viewed by 5190

Abstract

Protein kinase CK2 has been considered as an attractive therapeutic target of cancer therapy. The tricyclic quinoline compound CX-4945 is the first representative of CK2 inhibitors used in human clinical trials. The binding of non-2,6-naphtyridine substituted compounds 27e (IC₅₀ > 500 nM) [...] Read more.

Protein kinase CK2 has been considered as an attractive therapeutic target of cancer therapy. The tricyclic quinoline compound CX-4945 is the first representative of CK2 inhibitors used in human clinical trials. The binding of non-2,6-naphtyridine substituted compounds 27e (IC₅₀ > 500 nM) and 27h (IC₅₀ > 1000 nM) to CK2 is abolished. However, the unbinding mechanisms due to the key pharmacophore group replacement of compounds 27e and 27h are unveiled. In the present work, combined computational analysis was performed to investigate the underlying structural basis of the low-affinity of two systems. As indicated in the results, the loss of hydrogen bonds between the non-2,6-naphtyridine and the hinge region destroyed the proper recognition of the two complexes. Besides, the allosteric mechanisms between the deviated ligands and the changed regions (G-loop, C-loop and β4/β5 loop) are proposed. Furthermore, energetic analysis was evaluated by detailed energy calculation and residue-based energy decomposition. More importantly, the summary of known polar pharmacophore groups elucidates the pivotal roles of hinge region sub-pocket in the binding of CK2 inhibitors. These results provide rational clues to the fragment-based design of more potent CK2 inhibitors. Full article

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

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12 pages, 413 KiB

Open AccessArticle

Synthesis of 1,2,3-Triazolo[4,5-h]quinolone Derivatives with Novel Anti-Microbial Properties against Metronidazole Resistant Helicobacter pylori

by Mohammad Abu-Sini¹

, Amal Mayyas², Nehaya Al-Karablieh³

, Rula Darwish⁴, Yusuf Al-Hiari⁴, Talal Aburjai⁴, Shereen Arabiyat⁵ and Luay Abu-Qatouseh^6,*

¹ Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan

² Faculty of Health Sciences, American University of Madaba, Madaba 11821, Jordan

³ Hamdi Mango Center for Scientific Research, University of Jordan, Amman 11914, Jordan

⁴ Faculty of Pharmacy, University of Jordan, Amman 11914, Jordan

⁵ Salt College, Al-Balqa Applied University, As-Salt 19117, Jordan

⁶ Faculty of Pharmacy, University of Petra, Amman 11914, Jordan

Molecules 2017, 22(5), 841; https://doi.org/10.3390/molecules22050841 - 20 May 2017

Cited by 16 | Viewed by 6080

Abstract

Helicobacter pylori infection can lead to gastritis, peptic ulcer, and the development of mucosa associated lymphoid tissue (MALT) lymphoma. Treatment and eradication of H. pylori infection can prevent relapse and accelerate the healing of gastric and duodenal ulcers as well as regression of [...] Read more.

Helicobacter pylori infection can lead to gastritis, peptic ulcer, and the development of mucosa associated lymphoid tissue (MALT) lymphoma. Treatment and eradication of H. pylori infection can prevent relapse and accelerate the healing of gastric and duodenal ulcers as well as regression of malignancy. Due to the increasing emergence of antibiotic resistance among clinical isolates of H. pylori, alternative approaches using newly discovered antimicrobial agents in combination with the standard antibiotic regimens for the treatment of H. pylori are of major importance. The purpose of the present study was to investigate the effect of newly synthesized 8-amino 7-substituted fluoroquinolone and their correspondent cyclized triazolo derivatives when either alone or combined with metronidazole against metronidazole-resistant H. pylori. Based on standard antimicrobial susceptibility testing methods and checkerboard titration assay, all of the tested compounds showed interesting antimicrobial activity against 12 clinical strains of H. pylori, with best in vitro effect for compounds 4b and 4c. Fractional inhibitory concentration (FIC) mean values showed synergistic pattern in all compounds of Group 5. In addition, additive activities of some of the tested compounds of Group 4 were observed when combined with metronidazole. In contrast, the tested compounds showed no significant urease inhibition activity. These results support the potential of new fluoroquinolone derivatives to be useful in combination with anti-H. pylori drugs in the management of H. pylori-associated diseases. Full article

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

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6 pages, 889 KiB

Open AccessArticle

Three New Abietane-Type Diterpenoids from Callicarpa macrophylla Vahl.

by Zhen-Hui Wang^*, Chao Niu, De-Jun Zhou, Ji-Chuan Kong and Wen-Kui Zhang

College of Medicine, Henan Polytechnic University, Jiaozuo 454000, China

Molecules 2017, 22(5), 842; https://doi.org/10.3390/molecules22050842 - 19 May 2017

Cited by 15 | Viewed by 5764

Abstract

Three new abietane-type diterpenoids, named callicapoic acid M3 (1), callicapoic acid M4 (2) and callicapoic acid M5 (3), were isolated from the Callicarpa macrophylla Vahl. Their structures were established by spectroscopic techniques (IR, UV, MS, 1D and [...] Read more.

Three new abietane-type diterpenoids, named callicapoic acid M3 (1), callicapoic acid M4 (2) and callicapoic acid M5 (3), were isolated from the Callicarpa macrophylla Vahl. Their structures were established by spectroscopic techniques (IR, UV, MS, 1D and 2D NMR). All the isolated three compounds were evaluated for inhibitory activity on NO production in LPS-activated RAW 264.7 macrophage cells by using MTT assays. Compounds 1, 2 and 3 showed potent inhibitory activity, with inhibition rates of 34.47–40.13%. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 1046 KiB

Open AccessCommunication

Rapidly Simultaneous Determination of Six Effective Components in Cistanche tubulosa by Near Infrared Spectroscopy

by Xinhong Wang

, Xiaoguang Wang and Yuhai Guo^*

College of Agronomy, China Agricultural University, Yuanming Yuan West Road, Haidian District, Beijing 100193, China

Molecules 2017, 22(5), 843; https://doi.org/10.3390/molecules22050843 - 19 May 2017

Cited by 28 | Viewed by 5378

Abstract

Quantitative determination of multiple effective components in a given plant usually requires a very large amount of authentic natural products. In this study, we proposed a rapid and non-destructive method for the simultaneous determination of echinacoside, verbascoside, mannitol, sucrose, glucose and fructose in [...] Read more.

Quantitative determination of multiple effective components in a given plant usually requires a very large amount of authentic natural products. In this study, we proposed a rapid and non-destructive method for the simultaneous determination of echinacoside, verbascoside, mannitol, sucrose, glucose and fructose in Cistanche tubulosa by near infrared spectroscopy (NIRS). Near infrared diffuse reflectance spectroscopy (DRS) and high performance liquid chromatography (HPLC) were conducted on 116 batches of C. tubulosa samples. The DRS data were processed using standard normal variety (SNV) and multiplicative scatter correction (MSC) methods. Partial least squares regression (PLSR) was utilized to build calibration models for components-of-interest in C. tubulosa. All models were then assessed by calculating the root mean square error of calibration (RMSEC), correlation coefficient of calibration (r). The r values of all six calibration models were determined to be greater than 0.94, suggesting each model is reliable. Therefore, the quantitative NIR models reported in this study can be qualified to accurately quantify the contents of six medicinal components in C. tubulosa. Full article

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15 pages, 2176 KiB

Open AccessArticle

Enhanced Production of Gypenoside LXXV Using a Novel Ginsenoside-Transforming β-Glucosidase from Ginseng-Cultivating Soil Bacteria and Its Anti-Cancer Property

by Chang-Hao Cui¹, Da Jung Kim², Suk-Chae Jung¹, Sun-Chang Kim^1,2,3,* and Wan-Taek Im^4,*

¹ Intelligent Synthetic Biology Center, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Korea

² Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Korea

³ KAIST Institute for Biocentury, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Korea

⁴ Department of Biological Sciences, Hankyong National University, 327 Chungang-no Anseong-si, Kyonggi-do 456-749, Korea

Molecules 2017, 22(5), 844; https://doi.org/10.3390/molecules22050844 - 19 May 2017

Cited by 38 | Viewed by 7120

Abstract

Minor ginsenosides, such as compound K, Rg₃(S), which can be produced by deglycosylation of ginsenosides Rb₁, showed strong anti-cancer effects. However, the anticancer effects of gypenoside LXXV, which is one of the deglycosylated shapes of ginsenoside Rb [...] Read more.

Minor ginsenosides, such as compound K, Rg₃(S), which can be produced by deglycosylation of ginsenosides Rb₁, showed strong anti-cancer effects. However, the anticancer effects of gypenoside LXXV, which is one of the deglycosylated shapes of ginsenoside Rb₁, is still unknown due to the rarity of its content in plants. Here, we cloned and characterized a novel ginsenoside-transforming β-glucosidase (BglG167b) derived from Microbacterium sp. Gsoil 167 which can efficiently hydrolyze gypenoside XVII into gypenoside LXXV, and applied it to the production of gypenoside LXXV at the gram-scale with high specificity. In addition, the anti-cancer activity of gypenoside LXXV was investigated against three cancer cell lines (HeLa, B16, and MDA-MB231) in vitro. Gypenoside LXXV significantly reduced cell viability, displaying an enhanced anti-cancer effect compared to gypenoside XVII and Rb₁. Taken together, this enzymatic method would be useful in the preparation of gypenoside LXXV for the functional food and pharmaceutical industries. Full article

(This article belongs to the Special Issue Synthesis and Modification of Natural Product)

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13 pages, 5547 KiB

Open AccessArticle

Preparation and In Vitro Photodynamic Activity of Glucosylated Zinc(II) Phthalocyanines as Underlying Targeting Photosensitizers

by Jian-Yong Liu^1,*, Chen Wang¹, Chun-Hui Zhu¹, Zhi-Hong Zhang^2,* and Jin-Ping Xue¹

¹ State Key Laboratory of Photocatalysis on Energy and Environment & National & Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, College of Chemistry, Fuzhou University, Fuzhou 350108, China

² Fuzhou General Hospital of Nanjing Military Command, Fuzhou 350005, China

Molecules 2017, 22(5), 845; https://doi.org/10.3390/molecules22050845 - 19 May 2017

Cited by 15 | Viewed by 5813

Abstract

Two novel glucosylated zinc(ІІ) phthalocyanines 7a–7b, as well as the acetyl-protected counterparts 6a–6b, have been synthesized by the Cu(I)-catalyzed 1,3-dipolar cycloaddition between the propargylated phthalocyanine and azide-substituted glucoses. All of these phthalocyanines were characterized with various spectroscopic methods and studied for their photo-physical, [...] Read more.

Two novel glucosylated zinc(ІІ) phthalocyanines 7a–7b, as well as the acetyl-protected counterparts 6a–6b, have been synthesized by the Cu(I)-catalyzed 1,3-dipolar cycloaddition between the propargylated phthalocyanine and azide-substituted glucoses. All of these phthalocyanines were characterized with various spectroscopic methods and studied for their photo-physical, photo-chemical, and photo-biological properties. With glucose as the targeting unit, phthalocyanines 7a–7b exhibit a specific affinity to MCF-7 breast cancer cells over human embryonic lung fibroblast (HELF) cells, showing higher cellular uptake. Upon illumination, both photosensitizers show high cytotoxicity with IC₅₀ as low as 0.032 µM toward MCF-7 cells, which are attributed to their high cellular uptake and low aggregation tendency in the biological media, promoting the generation of intracellular reactive oxygen species (ROS). Confocal laser fluorescence microscopic studies have also revealed that they have high and selective affinities to the lysosomes, but not the mitochondria, of MCF-7 cells. The results show that these two glucosylated zinc(II) phthalocyanines are potential anticancer agents for targeting photodynamic therapy. Full article

(This article belongs to the Special Issue Porphyrins and Phthalocyanines: Synthesis, Properties and Applications)

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23 pages, 4430 KiB

Open AccessArticle

Study on the Alkylation Reactions of N(7)-Unsubstituted 1,3-Diazaoxindoles

by Eszter Kókai^1,2,3, Judit Halász¹, András Dancsó¹

, József Nagy², Gyula Simig¹ and Balázs Volk^1,*

¹ Directorate of Drug Substance Development, Egis Pharmaceuticals Plc., P.O. Box 100, 1475 Budapest, Hungary

² Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, P.O. Box 91, 1521 Budapest, Hungary

³ Department of Materials Technology, GAMF Faculty of Engineering and Computer Science, Pallasz Athéné University, P.O. Box 700, 6001 Kecskemét, Hungary

Molecules 2017, 22(5), 846; https://doi.org/10.3390/molecules22050846 - 19 May 2017

Cited by 3 | Viewed by 7260

Abstract

The chemistry of the 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one (1,3-diazaoxindole) compound family, possessing a drug-like scaffold, is unexplored. In this study, the alkylation reactions of N(7)-unsubstituted 5-isopropyl-1,3-diazaoxindoles bearing various substituents at the C(2) position have been investigated. The starting compounds were [...] Read more.

The chemistry of the 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one (1,3-diazaoxindole) compound family, possessing a drug-like scaffold, is unexplored. In this study, the alkylation reactions of N(7)-unsubstituted 5-isopropyl-1,3-diazaoxindoles bearing various substituents at the C(2) position have been investigated. The starting compounds were synthesized from the C(5)-unsubstituted parent compounds by condensation with acetone and subsequent catalytic reduction of the 5-isopropylidene moiety. Alkylation of the thus obtained 5-isopropyl derivatives with methyl iodide or benzyl bromide in the presence of a large excess of sodium hydroxide led to 5,7-disubstituted derivatives. Use of butyllithium as the base rendered alkylation in the C(5) position possible with reasonable selectivity, without affecting the N(7) atom. During the study on the alkylation reactions, some interesting by-products were also isolated and characterized. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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12 pages, 1657 KiB

Open AccessArticle

Functional Mitochondria Are Important for the Effect of Resveratrol

by Anne L. Widlund, Kaushal Baral, Louise T. Dalgaard

and Ole Vang^*

Department of Science and Environment, Roskilde University, Roskilde DK-4000, Denmark

Molecules 2017, 22(5), 847; https://doi.org/10.3390/molecules22050847 - 20 May 2017

Cited by 9 | Viewed by 7880

Abstract

Resveratrol (Resv) is a polyphenol reported to modulate mitochondrial activity. The aim was to use HeLa and 143B cells to characterize the action of Resv on mitochondrial activity, cell size and proliferation using wild type (WT) and Rho 0 cells deficient in mitochondrial [...] Read more.

Resveratrol (Resv) is a polyphenol reported to modulate mitochondrial activity. The aim was to use HeLa and 143B cells to characterize the action of Resv on mitochondrial activity, cell size and proliferation using wild type (WT) and Rho 0 cells deficient in mitochondrial DNA. In both HeLa WT and Rho 0 cells, the oxygen consumption rate (OCR) was increased at 20 µM Resv after 24 h, whereas only a non-significant increase of OCR was observed in 143B WT cells. Resv decreased cell number concentration-dependently in both WT and Rho 0 cell types. An increased cell diameter was observed in HeLa WT, but not in Rho 0 when treated with Resv. Overall, the findings presented indicate that functional mitochondria are a prerequisite for cell enlargement by Resv. Full article

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

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10 pages, 1027 KiB

Open AccessArticle

Photoreactions of Endohedral Metallofullerene with Siliranes: Electronic Properties of Carbosilylated Lu₃N@I_h-C₈₀

by Masahiro Kako^1,*, Kazuya Minami¹, Taiki Kuroiwa¹, Shinpei Fukazawa¹, Yuki Arikawa¹, Michio Yamada²

, Yutaka Maeda², Qiao-Zhi Li³, Shigeru Nagase^3,* and Takeshi Akasaka^2,4,5,6,*

¹ Department of Engineering Science, The University of Electro-Communications, Chofu 182-8585, Japan

² Department of Chemistry, Tokyo Gakugei University, Tokyo 184-8501, Japan

³ Fukui Institute for Fundamental Chemistry, Kyoto University, Kyoto 606-8103, Japan

⁴ Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki 305-8577, Japan

⁵ Foundation for Advancement of International Science, Ibaraki 305-0821, Japan

⁶ School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074, China

Molecules 2017, 22(5), 850; https://doi.org/10.3390/molecules22050850 - 20 May 2017

Cited by 3 | Viewed by 4471

Abstract

Photochemical carbosilylation of Lu₃N@I_h-C₈₀ was performed using siliranes (silacyclopropanes) to afford the corresponding [5,6]- and [6,6]-adducts. Electrochemical studies indicated that the redox potentials of the carbosilylated derivatives were shifted cathodically in comparison with those of the [5,6]-pyrrolidino [...] Read more.

Photochemical carbosilylation of Lu₃N@I_h-C₈₀ was performed using siliranes (silacyclopropanes) to afford the corresponding [5,6]- and [6,6]-adducts. Electrochemical studies indicated that the redox potentials of the carbosilylated derivatives were shifted cathodically in comparison with those of the [5,6]-pyrrolidino adducts. The electronic effect of the silirane addends on Lu₃N@I_h-C₈₀ was verified on the basis of density functional theory calculations. Full article

(This article belongs to the Special Issue Cutting-Edge Organic Chemistry in Japan)

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15 pages, 6174 KiB

Open AccessArticle

Rapid and Cost-Effective Quantification of Glucosinolates and Total Phenolic Content in Rocket Leaves by Visible/Near-Infrared Spectroscopy

by Eva María Toledo-Martín¹, Rafael Font², Sara Obregón-Cano³

, Antonio De Haro-Bailón³

, Myriam Villatoro-Pulido³ and Mercedes Del Río-Celestino^1,*

¹ Department of Genomics and Biotecnology, IFAPA Center La Mojonera, Camino San Nicolás, La Mojonera 1, 04745 Almería, Spain

² Department of Food and Health, IFAPA Center La Mojonera, Camino San Nicolás, La Mojonera 1, 04745 Almería, Spain

³ Department of Agronomy and Plant Breeding, Institute of Sustainable Agriculture, (CSIC), Alameda del Obispo s/n, 14080 Córdoba, Spain

Molecules 2017, 22(5), 851; https://doi.org/10.3390/molecules22050851 - 20 May 2017

Cited by 25 | Viewed by 6171

Abstract

The potential of visible-near infrared spectroscopy to predict glucosinolates and total phenolic content in rocket (Eruca vesicaria) leaves has been evaluated. Accessions of the E. vesicaria species were scanned by NIRS as ground leaf, and their reference values regressed against different [...] Read more.

The potential of visible-near infrared spectroscopy to predict glucosinolates and total phenolic content in rocket (Eruca vesicaria) leaves has been evaluated. Accessions of the E. vesicaria species were scanned by NIRS as ground leaf, and their reference values regressed against different spectral transformations by modified partial least squares (MPLS) regression. The coefficients of determination in the external validation (R²VAL) for the different quality components analyzed in rocket ranged from 0.59 to 0.84, which characterize those equations as having from good to excellent quantitative information. These results show that the total glucosinolates, glucosativin and glucoerucin equations obtained, can be used to identify those samples with low and high contents. The glucoraphanin equation obtained can be used for rough predictions of samples and in case of total phenolic content, the equation showed good correlation. The standard deviation (SD) to standard error of prediction ratio (RPD) and SD to range (RER) were variable for the different quality compounds and showed values that were characteristic of equations suitable for screening purposes or to perform accurate analyses. From the study of the MPLS loadings of the first three terms of the different equations, it can be concluded that some major cell components such as protein and cellulose, highly participated in modelling the equations for glucosinolates. Full article

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13 pages, 907 KiB

Open AccessArticle

Synthesis and Excellent Duplex Stability of Oligonucleotides Containing 2′-Amino-LNA Functionalized with Galactose Units

by Rajesh Kumar^1,2, Annika Ries¹ and Jesper Wengel^1,*

¹ Biomolecular Nanoscale Engineering Center, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark

² Department of Chemistry, University of Delhi, Delhi 110007, India

Molecules 2017, 22(5), 852; https://doi.org/10.3390/molecules22050852 - 21 May 2017

Cited by 8 | Viewed by 7639

Abstract

A convenient method for the preparation of oligonucleotides containing internally-attached galactose and triantennary galactose units has been developed based on click chemistry between 2′-N-alkyne 2′-amino-LNA nucleosides and azido-functionalized galactosyl building blocks. The synthesized oligonucleotides show excellent binding affinity and selectivity towards [...] Read more.

A convenient method for the preparation of oligonucleotides containing internally-attached galactose and triantennary galactose units has been developed based on click chemistry between 2′-N-alkyne 2′-amino-LNA nucleosides and azido-functionalized galactosyl building blocks. The synthesized oligonucleotides show excellent binding affinity and selectivity towards complementary DNA/RNA strands with an increase in the melting temperature of up to +23.5 °C for triply-modified variants. Full article

(This article belongs to the Special Issue Synthesis and Applications of Oligonucleotide Conjugates)

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17 pages, 973 KiB

Open AccessArticle

Phytochemical Composition and Antioxidant Capacity of Seven Saskatoon Berry (Amelanchier alnifolia Nutt.) Genotypes Grown in Poland

by Sabina Lachowicz^1,*, Jan Oszmiański¹, Łukasz Seliga² and Stanisław Pluta²

¹ Department of Fruit, Vegetables and Plant Nutraceutical Technology, Wrocław University of Environmental and Life Science, 37, Chełmońskiego Street, 51-630 Wrocław, Poland

² Department of Horticultural Crop Breeding, Research Institute of Horticulture, Konstytucji 3 Maja 1/3, 96-100 Skierniewice, Poland

Molecules 2017, 22(5), 853; https://doi.org/10.3390/molecules22050853 - 21 May 2017

Cited by 51 | Viewed by 6797

Abstract

The basic chemical composition, bioactive compounds, and antioxidant capacity of fruits of three new Polish breeding clones (No. 5/6, type S, and type N) and four Canadian cultivars (cvs.) (“Martin”, “Smoky”, “Pembina”, and “Honeywood”) grown in Poland in 2016 were investigated. Fruits were [...] Read more.

The basic chemical composition, bioactive compounds, and antioxidant capacity of fruits of three new Polish breeding clones (No. 5/6, type S, and type N) and four Canadian cultivars (cvs.) (“Martin”, “Smoky”, “Pembina”, and “Honeywood”) grown in Poland in 2016 were investigated. Fruits were analyzed for their contents of triterpenoids, carotenoids, chlorophylls, and polyphenolics with the ultra-performance liquid chromatography photodiode detector-quadrupole/time-of-flight mass spectrometry (UPLC-PDA-Q/TOF-MS) method, sugar with the high-performance liquid chromatography–evaporative light scattering detector (HPLC-ELSD) method, and antioxidant capacity with the ability to reduce free radical (ABTS) and ferric reducing ability of plasma (FRAP) method. Thirty-eight bioactive compounds, including twenty-eight polyphenolic compounds (four anthocyanins, nine phenolic acids, nine flavonols, and seven flavan-3-ols), four carotenoids, two chlorophylls, and three triterpenoids were identified in the fruits. The fruits of the tested Saskatoon berry genotypes were found to be rich in phenolic compounds (3773.94–6390.36 mg/100 g·dm), triterpenoids (66.55–91.31 mg/kg·dm), and carotenoids (478.62–561.57 mg/kg·dm), with high ABTS and FRAP capacity (10.38–34.49 and 9.66–25.34 mmol·Trolox/100 g·dm, respectively). Additionally, the berries of these genotypes seemed to be a good source of sugar (9.02–19.69 g/100 g), pectins (0.67%–1.33%), and ash (0.59%–0.67%). Some genotypes of Saskatoon berry, especially the clones type S, type N, and cvs. “Honeywood” and “Smoky”, may be selected for their potential applications in commercial cultivation to produce fruits with valuable health-promoting nutritional effects on human health. Additionally, three new genotypes that may offer new functional materials can be recommended for fruit growers. Full article

(This article belongs to the Section Natural Products Chemistry)

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19 pages, 4683 KiB

Open AccessArticle

A 4-Phenoxyphenol Derivative Exerts Inhibitory Effects on Human Hepatocellular Carcinoma Cells through Regulating Autophagy and Apoptosis Accompanied by Downregulating α-Tubulin Expression

by Wen-Tsan Chang^1,2,†, Wangta Liu^3,†

, Yi-Han Chiu⁴, Bing-Hung Chen^3,5, Shih-Chang Chuang^1,6,7, Yen-Chun Chen³, Yun-Tzh Hsu³, Mei-Jei Lu³, Shean-Jaw Chiou⁸, Chon-Kit Chou³ and Chien-Chih Chiu^{3,9,10,11,12,*}

¹ Division of General and Digestive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan

² Department of Surgery, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan

³ Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan

⁴ Department of Nursing, St. Mary’s Junior College of Medicine, Nursing and Management, Yi-Lan 266, Taiwan

⁵ The Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan

⁶ Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan

⁷ Transplantation Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan

⁸ Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan

⁹ Translational Research Center, Cancer Center, Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan

¹⁰ Research Center for Environment Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan

¹¹ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan

¹² Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan

^† These authors contributed equally to this work.

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Molecules 2017, 22(5), 854; https://doi.org/10.3390/molecules22050854 - 21 May 2017

Cited by 20 | Viewed by 6913

Abstract

Hepatocellular carcinoma (HCC) is a leading cancer worldwide. Advanced HCCs are usually resistant to anticancer drugs, causing unsatisfactory chemotherapy outcomes. In this study, we showed that a 4-phenoxyphenol derivative, 4-[4-(4-hydroxyphenoxy)phenoxy]phenol (4-HPPP), exerts an inhibitory activity against two HCC cell lines, Huh7 and Ha22T. [...] Read more.

Hepatocellular carcinoma (HCC) is a leading cancer worldwide. Advanced HCCs are usually resistant to anticancer drugs, causing unsatisfactory chemotherapy outcomes. In this study, we showed that a 4-phenoxyphenol derivative, 4-[4-(4-hydroxyphenoxy)phenoxy]phenol (4-HPPP), exerts an inhibitory activity against two HCC cell lines, Huh7 and Ha22T. We further investigated the anti-HCC activities of 4-HPPP, including anti-proliferation and induction of apoptosis. Our results showed that higher dosage of 4-HPPP downregulates the expression of α-tubulin and causes nuclear enlargement in both the Huh-7 and Ha22T cell lines. Interestingly, the colony formation results showed a discrepancy in the inhibitory effect of 4-HPPP on HCC and rat liver epithelial Clone 9 cells, suggesting the selective cytotoxicity of 4-HPPP toward HCC cells. Furthermore, the cell proliferation and apoptosis assay results illustrated the differences between the two HCC cell lines. The results of cellular proliferation assays, including trypan blue exclusion and colony formation, revealed that 4-HPPP inhibits the growth of Huh7 cells, but exerts less cytotoxicity in Ha22T cells. Furthermore, the annexin V assay performed for detecting the apoptosis showed similar results. Western blotting results showed 4-HPPP caused the increase of pro-apoptotic factors including cleaved caspase-3, Bid and Bax in HCC cells, especially in Huh-7. Furthermore, an increase of autophagy-associated protein microtubule-associated protein-1 light chain-3B (LC3B)-II and the decrease of Beclin-1 and p62/SQSTM1 were observed following 4-HPPP treatment. Additionally, the level of γH2A histone family, member X (γH₂AX), an endogenous DNA damage biomarker, was dramatically increased in Huh7 cells after 4-HPPP treatment, suggesting the involvement of DNA damage pathway in 4-HPPP-induced apoptosis. On the contrary, the western blotting results showed that treatment up-regulates pro-survival proteins, including the phosphorylation of protein kinase B (Akt) and the level of survivin on Ha22T cells, which may confer a resistance toward 4-HPPP. Notably, the blockade of extracellular signal-regulated kinases (ERK), but not Akt, enhanced the cytotoxicity of 4-HPPP against Ha22T cells, indicating the pro-survival role of ERK in 4-HPPP-induced anti-HCC effect. Our present work suggests that selective anti-HCC activity of 4-HPPP acts through induction of DNA damage. Accordingly, the combination of ERK inhibitor may significantly enhance the anti-cancer effect of 4-HPPP for those HCC cells which overexpress ERK in the future. Full article

(This article belongs to the Special Issue Tubulin Inhibitors)

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9 pages, 1071 KiB

Open AccessArticle

Synthesis and Characterization of Constrained Geometry Oxygen and Sulphur Functionalized Cyclopentadienylchromium Complexes and Their Use in Catalysis for Olefin Polymerization

by Ruiguo Zhao^1,2, Jun Ma², Hao Zhang^1,2,* and Jiling Huang^2,*

¹ School of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot 010021, China

² The Laboratory of Organometallic Chemistry, East China University of Science and Technology, Shanghai 200237, China

Molecules 2017, 22(5), 856; https://doi.org/10.3390/molecules22050856 - 22 May 2017

Cited by 9 | Viewed by 5686

Abstract

A series of constrained geometry O-functionalized cyclopentadienylchromium complexes (1–6) and a S-functionalized cyclopentadienylchromium complex (7) were first synthesized, characterized, and tested as catalyst precursors for the olefin polymerization. In the presence of MAO, the complexes exhibited high [...] Read more.

A series of constrained geometry O-functionalized cyclopentadienylchromium complexes (1–6) and a S-functionalized cyclopentadienylchromium complex (7) were first synthesized, characterized, and tested as catalyst precursors for the olefin polymerization. In the presence of MAO, the complexes exhibited high catalytic activity for the polymerization of ethylene. It is shown that ligand variations can have a substantial effect on catalyst activity and stability. The effect of Al/Cr ratio on catalytic activity was also studied. Full article

(This article belongs to the Special Issue Organometallic Catalysis for Olefin Polymerization/Oligomerization)

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10 pages, 3882 KiB

Open AccessArticle

CTAB-Assisted Fabrication of Bi₂WO₆ Thin Nanoplates with High Adsorption and Enhanced Visible Light-Driven Photocatalytic Performance

by Yuxue Zhou, Pengfei Lv, Xiangdong Meng, Yanping Tang, Pingping Huang, Xiaobing Chen, Xiaoshuang Shen^* and Xianghua Zeng^*

School of Physical Science & Technology, Yangzhou University, Yangzhou 225002, China

Molecules 2017, 22(5), 859; https://doi.org/10.3390/molecules22050859 - 22 May 2017

Cited by 26 | Viewed by 6379

Abstract

Two-dimensional thin Bi₂WO₆ nanoplates have been fabricated using a cetyltrimethylammonium bromide (CTAB)-assisted hydrothermal method. We investigated the proposed formation mechanism based on the crystalline structures of the thin Bi₂WO₆ nanoplates. The high adsorption ability and excellent visible-light [...] Read more.

Two-dimensional thin Bi₂WO₆ nanoplates have been fabricated using a cetyltrimethylammonium bromide (CTAB)-assisted hydrothermal method. We investigated the proposed formation mechanism based on the crystalline structures of the thin Bi₂WO₆ nanoplates. The high adsorption ability and excellent visible-light driven photocatalytic activities of the Bi₂WO₆ nanoplates were illustrated, in view of exposed (001) facets of nanoplates possessing faster separation of photo-generated charge carriers and increased catalytically active sites. Such a cost-effective way to obtain Bi₂WO₆ nanoplates offers new possibilities for the design of adsorptive semiconductor photocatalysts with strengthened photocatalytic activities. Full article

(This article belongs to the Special Issue Nanocrystals: Synthesis, Characterization and Applications)

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11 pages, 3105 KiB

Open AccessArticle

Development of Optimized Inhibitor RNAs Allowing Multisite-Targeting of the HCV Genome

by Cristina Romero-López^*, Thomas Lahlali^†, Beatriz Berzal-Herranz and Alfredo Berzal-Herranz^*

¹ Instituto de Parasitología y Biomedicina “López-Neyra”, IPBLN-CSIC, PTS Granada, Av. del Conocimiento 17, Armilla, 18016 Granada, Spain

^† Current address: INSERM U1052, Cancer Research Centre of Lyon (CRCL), Université Claude-Bernard (UCBL), UMR_S1052, UCBL, 69008 Lyon, France.

Molecules 2017, 22(5), 861; https://doi.org/10.3390/molecules22050861 - 22 May 2017

Cited by 10 | Viewed by 5121

Abstract

Engineered multivalent drugs are promising candidates for fighting infection by highly variable viruses, such as HCV. The combination into a single molecule of more than one inhibitory domain, each with its own target specificity and even a different mechanism of action, results in [...] Read more.

Engineered multivalent drugs are promising candidates for fighting infection by highly variable viruses, such as HCV. The combination into a single molecule of more than one inhibitory domain, each with its own target specificity and even a different mechanism of action, results in drugs with potentially enhanced therapeutic properties. In the present work, the anti-HCV chimeric inhibitor RNA HH363-10, which has a hammerhead catalytic domain and an aptamer RNA domain, was subjected to an in vitro selection strategy to isolate ten different optimised chimeric inhibitor RNAs. The catalytic domain was preserved while the aptamer RNA domain was evolved to contain two binding sites, one mapping to the highly conserved IIIf domain of the HCV genome’s internal ribosome entry site (IRES), and the other either to IRES domain IV (which contains the translation start codon) or the essential linker region between domains I and II. These chimeric molecules efficiently and specifically interfered with HCV IRES-dependent translation in vitro (with IC₅₀ values in the low µM range). They also inhibited both viral translation and replication in cell culture. These findings highlight the feasibility of using in vitro selection strategies for obtaining improved RNA molecules with potential clinical applications. Full article

(This article belongs to the Special Issue Synthesis and Applications of Oligonucleotide Conjugates)

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Review

Jump to: Editorial, Research

24 pages, 3686 KiB

Open AccessReview

Innovative “Green” and Novel Strategies for the Extraction of Bioactive Added Value Compounds from Citrus Wastes—A Review

by Predrag Putnik¹, Danijela Bursać Kovačević¹

, Anet Režek Jambrak¹

, Francisco J. Barba²

, Giancarlo Cravotto^3,*

, Arianna Binello³

, Jose Manuel Lorenzo⁴

and Avi Shpigelman⁵

¹ Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, Croatia

² Nutrition and Food Science Area, Preventive Medicine and Public Health, Food Science, Toxicology and Forensic Medicine Department, Faculty of Pharmacy, Universitat de València, Avda. Vicent Andrés Estellés, s/n, 46100 Burjassot, Spain

³ Dipartimento di Scienza e Tecnologia del Farmaco, University of Turin, Via P. Giuria 9, Turin 10125, Italy

⁴ Centro Tecnológico de la Carne de Galicia, c/Galicia, 4, San Ciprián de Viñas, 32900 Ourense, Spain

⁵ Faculty of Biotechnology and Food Engineering, Technion, Israel Institute of Technology, Haifa 3200003, Israel

Molecules 2017, 22(5), 680; https://doi.org/10.3390/molecules22050680 - 27 Apr 2017

Cited by 270 | Viewed by 20703

Abstract

Citrus is a major processed crop that results in large quantities of wastes and by-products rich in various bioactive compounds such as pectins, water soluble and insoluble antioxidants and essential oils. While some of those wastes are currently valorised by various technologies (yet [...] Read more.

Citrus is a major processed crop that results in large quantities of wastes and by-products rich in various bioactive compounds such as pectins, water soluble and insoluble antioxidants and essential oils. While some of those wastes are currently valorised by various technologies (yet most are discarded or used for feed), effective, non-toxic and profitable extraction strategies could further significantly promote the valorisation and provide both increased profits and high quality bioactives. The present review will describe and summarize the latest works concerning novel and greener methods for valorisation of citrus by-products. The outcomes and effectiveness of those technologies such as microwaves, ultrasound, pulsed electric fields and high pressure is compared both to conventional valorisation technologies and between the novel technologies themselves in order to highlight the advantages and potential scalability of these so-called “enabling technologies”. In many cases the reported novel technologies can enable a valorisation extraction process that is “greener” compared to the conventional technique due to a lower energy consumption and reduced utilization of toxic solvents. Full article

(This article belongs to the Special Issue Green Production of Bioactive Natural Products)

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13 pages, 1107 KiB

Open AccessReview

Oleuropein and Cancer Chemoprevention: The Link is Hot

by Ammad Ahmad Farooqi¹

, Sundas Fayyaz¹, Ana Sanches Silva^2,3, Antoni Sureda⁴

, Seyed Fazel Nabavi⁵, Andrei Mocan^6,7, Seyed Mohammad Nabavi^5,* and Anupam Bishayee^8,*

¹ Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College, Lahore 54000, Pakistan

² Department of Food and Nutrition, National Institute of Health Dr. Ricardo Jorge, I.P., Av. Padre Cruz, 1649-016 Lisbon, Portugal

³ Center for Study in Animal Science, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal

⁴ Research Group on Community Nutrition and Oxidative Stress and CIBEROBN—Physiopathology of Obesity and Nutrition, University of Balearic Islands, Palma de Mallorca E-07122, Balearic Islands, Spain

⁵ Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran 1435916471, Iran

⁶ Department of Pharmaceutical Botany, Iuliu Hațieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania

⁷ ICHAT and Institute for Life Sciences, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3-5, 400372 Cluj-Napoca, Romania

⁸ Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL 33169, USA

Molecules 2017, 22(5), 705; https://doi.org/10.3390/molecules22050705 - 29 Apr 2017

Cited by 53 | Viewed by 9024

Abstract

Cancer comprises a collection of related diseases characterized by the existence of altered cellular pathways resulting in an abnormal tendency for uncontrolled growth. A broad spectrum, coordinated, and personalized approach focused on targeting diverse oncogenic pathways with low toxicity and economic natural compounds [...] Read more.

Cancer comprises a collection of related diseases characterized by the existence of altered cellular pathways resulting in an abnormal tendency for uncontrolled growth. A broad spectrum, coordinated, and personalized approach focused on targeting diverse oncogenic pathways with low toxicity and economic natural compounds can provide a real benefit as a chemopreventive and/or treatment of this complex disease. Oleuropein, a bioactive phenolic compound mainly present in olive oil and other natural sources, has been reported to modulate several oncogenic signalling pathways. This review presents and critically discusses the available literature about the anticancer and onco-suppressive activity of oleuropein and the underlying molecular mechanisms implicated in the anticarcinogenic and therapeutic effects. The existence of limitations and the promising perspectives of research on this phenolic compound are also critically analyzed and discussed. Full article

(This article belongs to the Special Issue Cancer Chemoprevention)

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49 pages, 8407 KiB

Open AccessReview

Sampling Terrestrial Environments for Bacterial Polyketides

by Patrick Hill¹, Graham W. Heberlig² and Christopher N. Boddy^1,2,*

¹ Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada

² Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON K1N 6N5, Canada

Molecules 2017, 22(5), 707; https://doi.org/10.3390/molecules22050707 - 29 Apr 2017

Cited by 10 | Viewed by 9270

Abstract

Bacterial polyketides are highly biologically active molecules that are frequently used as drugs, particularly as antibiotics and anticancer agents, thus the discovery of new polyketides is of major interest. Since the 1980s discovery of polyketides has slowed dramatically due in large part to [...] Read more.

Bacterial polyketides are highly biologically active molecules that are frequently used as drugs, particularly as antibiotics and anticancer agents, thus the discovery of new polyketides is of major interest. Since the 1980s discovery of polyketides has slowed dramatically due in large part to the repeated rediscovery of known compounds. While recent scientific and technical advances have improved our ability to discover new polyketides, one key area has been under addressed, namely the distribution of polyketide-producing bacteria in the environment. Identifying environments where producing bacteria are abundant and diverse should improve our ability to discover (bioprospect) new polyketides. This review summarizes for the bioprospector the state-of-the-field in terrestrial microbial ecology. It provides insight into the scientific and technical challenges limiting the application of microbial ecology discoveries for bioprospecting and summarizes key developments in the field that will enable more effective bioprospecting. The major recent efforts by researchers to sample new environments for polyketide discovery is also reviewed and key emerging environments such as insect associated bacteria, desert soils, disease suppressive soils, and caves are highlighted. Finally strategies for taking and characterizing terrestrial samples to help maximize discovery efforts are proposed and the inclusion of non-actinomycetal bacteria in any terrestrial discovery strategy is recommended. Full article

(This article belongs to the Special Issue Polyketides)

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11 pages, 1978 KiB

Open AccessReview

Heparin, Heparan Sulphate and the TGF-β Cytokine Superfamily

by Chris C. Rider^* and Barbara Mulloy

Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham, Surrey TW20 0EX, UK

Molecules 2017, 22(5), 713; https://doi.org/10.3390/molecules22050713 - 29 Apr 2017

Cited by 91 | Viewed by 9931

Abstract

Of the circa 40 cytokines of the TGF-β superfamily, around a third are currently known to bind to heparin and heparan sulphate. This includes TGF-β1, TGF-β2, certain bone morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs), as well as GDNF and two [...] Read more.

Of the circa 40 cytokines of the TGF-β superfamily, around a third are currently known to bind to heparin and heparan sulphate. This includes TGF-β1, TGF-β2, certain bone morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs), as well as GDNF and two of its close homologues. Experimental studies of their heparin/HS binding sites reveal a diversity of locations around the shared cystine-knot protein fold. The activities of the TGF-β cytokines in controlling proliferation, differentiation and survival in a range of cell types are in part regulated by a number of specific, secreted BMP antagonist proteins. These vary in structure but seven belong to the CAN or DAN family, which shares the TGF-β type cystine-knot domain. Other antagonists are more distant members of the TGF-β superfamily. It is emerging that the majority, but not all, of the antagonists are also heparin binding proteins. Any future exploitation of the TGF-β cytokines in the therapy of chronic diseases will need to fully consider their interactions with glycosaminoglycans and the implications of this in terms of their bioavailability and biological activity. Full article

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

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14 pages, 2236 KiB

Open AccessReview

Non-Chromatographic Purification of Endohedral Metallofullerenes

by Zhiyong Wang^1,2

, Haruka Omachi¹ and Hisanori Shinohara^1,*

¹ Department of Chemistry and Institute for Advanced Research, Nagoya University, Nagoya 464-8602, Japan

² Department of Chemistry, Renmin University of China, Beijing 100872, China

Molecules 2017, 22(5), 718; https://doi.org/10.3390/molecules22050718 - 29 Apr 2017

Cited by 10 | Viewed by 6491

Abstract

The purification of endohedral metallofullerenes by high performance liquid chromatography is very time-consuming and expensive. A number of rapid and inexpensive non-chromatographic methods have thus been developed for large-scale purification of metallofullerenes. In this review, we summarize recent advances in non-chromatographic purification methods [...] Read more.

The purification of endohedral metallofullerenes by high performance liquid chromatography is very time-consuming and expensive. A number of rapid and inexpensive non-chromatographic methods have thus been developed for large-scale purification of metallofullerenes. In this review, we summarize recent advances in non-chromatographic purification methods of metallofullerenes. Lewis acid-based complexation is one of the most efficient and powerful methods for separation of metallofullerenes from empty fullerenes. The first oxidation potential of metallofullerenes is a critical factor that affects the separation efficiency of the Lewis acid-based method. Supramolecular methods are effective for separation of fullerenes and metallofullerenes that are different in size and shape. Chemical/electrochemical reduction and exohedral functionalization are also utilized to separate and purify metallofullerenes on a large scale. Full article

(This article belongs to the Special Issue Endohedral Metallofullerenes)

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18 pages, 346 KiB

Open AccessReview

Heparin and Heparin-Derivatives in Post-Subarachnoid Hemorrhage Brain Injury: A Multimodal Therapy for a Multimodal Disease

by Erik G. Hayman¹, Akil P. Patel¹, Robert F. James² and J. Marc Simard^1,*

¹ Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA

² Department of Neurosurgery, University of Louisville, Louisville, KY 40208, USA

Molecules 2017, 22(5), 724; https://doi.org/10.3390/molecules22050724 - 2 May 2017

Cited by 29 | Viewed by 8762

Abstract

Pharmacologic efforts to improve outcomes following aneurysmal subarachnoid hemorrhage (aSAH) remain disappointing, likely owing to the complex nature of post-hemorrhage brain injury. Previous work suggests that heparin, due to the multimodal nature of its actions, reduces the incidence of clinical vasospasm and delayed [...] Read more.

Pharmacologic efforts to improve outcomes following aneurysmal subarachnoid hemorrhage (aSAH) remain disappointing, likely owing to the complex nature of post-hemorrhage brain injury. Previous work suggests that heparin, due to the multimodal nature of its actions, reduces the incidence of clinical vasospasm and delayed cerebral ischemia that accompany the disease. This narrative review examines how heparin may mitigate the non-vasospastic pathological aspects of aSAH, particularly those related to neuroinflammation. Following a brief review of early brain injury in aSAH and heparin’s general pharmacology, we discuss potential mechanistic roles of heparin therapy in treating post-aSAH inflammatory injury. These roles include reducing ischemia-reperfusion injury, preventing leukocyte extravasation, modulating phagocyte activation, countering oxidative stress, and correcting blood-brain barrier dysfunction. Following a discussion of evidence to support these mechanistic roles, we provide a brief discussion of potential complications of heparin usage in aSAH. Our review suggests that heparin’s use in aSAH is not only safe, but effectively addresses a number of pathologies initiated by aSAH. Full article

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

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25 pages, 1133 KiB

Open AccessReview

On the Many Actions of Ouabain: Pro-Cystogenic Effects in Autosomal Dominant Polycystic Kidney Disease

by Jessica Venugopal and Gustavo Blanco^*

Department of Molecular and Integrative Physiology, and The Kidney Institute, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160, USA

Molecules 2017, 22(5), 729; https://doi.org/10.3390/molecules22050729 - 3 May 2017

Cited by 17 | Viewed by 8345

Abstract

Ouabain and other cardenolides are steroidal compounds originally discovered in plants. Cardenolides were first used as poisons, but after finding their beneficial cardiotonic effects, they were rapidly included in the medical pharmacopeia. The use of cardenolides to treat congestive heart failure remained empirical [...] Read more.

Ouabain and other cardenolides are steroidal compounds originally discovered in plants. Cardenolides were first used as poisons, but after finding their beneficial cardiotonic effects, they were rapidly included in the medical pharmacopeia. The use of cardenolides to treat congestive heart failure remained empirical for centuries and only relatively recently, their mechanisms of action became better understood. A breakthrough came with the discovery that ouabain and other cardenolides exist as endogenous compounds that circulate in the bloodstream of mammals. This elevated these compounds to the category of hormones and opened new lines of investigation directed to further study their biological role. Another important discovery was the finding that the effect of ouabain was mediated not only by inhibition of the activity of the Na,K-ATPase (NKA), but by the unexpected role of NKA as a receptor and a signal transducer, which activates a complex cascade of intracellular second messengers in the cell. This broadened the interest for ouabain and showed that it exerts actions that go beyond its cardiotonic effect. It is now clear that ouabain regulates multiple cell functions, including cell proliferation and hypertrophy, apoptosis, cell adhesion, cell migration, and cell metabolism in a cell and tissue type specific manner. This review article focuses on the cardenolide ouabain and discusses its various in vitro and in vivo effects, its role as an endogenous compound, its mechanisms of action, and its potential use as a therapeutic agent; placing especial emphasis on our findings of ouabain as a pro-cystogenic agent in autosomal dominant polycystic kidney disease (ADPKD). Full article

(This article belongs to the Special Issue Cardiotonic Steroids)

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11 pages, 239 KiB

Open AccessReview

New Applications of Heparin and Other Glycosaminoglycans

by Marcelo Lima^1,2,*, Timothy Rudd^2,3,*

and Edwin Yates^1,2,*

¹ Department of Biochemistry, Federal University of São Paulo (UNIFESP), Vila Clementino, São Paulo, S.P. 04044-020, Brazil

² Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK

³ National Institute of Biological Standards and Controls (NIBSC), Blanche Lane, Potters Bar, Herts EN6 3QG, UK

Molecules 2017, 22(5), 749; https://doi.org/10.3390/molecules22050749 - 6 May 2017

Cited by 66 | Viewed by 8661

Abstract

Heparin, the widely used pharmaceutical anticoagulant, has been in clinical use for well over half a century. Its introduction reduced clotting risks substantially and subsequent developments, including the introduction of low-molecular-weight heparin, made possible many major surgical interventions that today make heparin an [...] Read more.

Heparin, the widely used pharmaceutical anticoagulant, has been in clinical use for well over half a century. Its introduction reduced clotting risks substantially and subsequent developments, including the introduction of low-molecular-weight heparin, made possible many major surgical interventions that today make heparin an indispensable drug. There has been a recent burgeoning of interest in heparin and related glycosaminoglycan (GAG) polysaccharides, such as chondroitin sulfates, heparan sulfate, and hyaluronate, as potential agents in various applications. This ability arises mainly from the ability of GAGs to interact with, and alter the activity of, a wide range of proteins. Here, we review new developments (since 2010) in the application of heparin and related GAGs across diverse fields ranging from thrombosis and neurodegenerative disorders to microbiology and biotechnology. Full article

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

27 pages, 305 KiB

Open AccessReview

The Adenosinergic System as a Therapeutic Target in the Vasculature: New Ligands and Challenges

by Joana Beatriz Sousa^1,2

and Carmen Diniz^1,2,*

¹ LAQV/REQUIMTE, Faculty of Pharmacy, University of Porto, 4050-047 Porto, Portugal

² Laboratory of Pharmacology, Department of Drug Science, Faculty of Pharmacy, University of Porto, 4050-047 Porto, Portugal

Molecules 2017, 22(5), 752; https://doi.org/10.3390/molecules22050752 - 6 May 2017

Cited by 30 | Viewed by 5734

Abstract

Adenosine is an adenine base purine with actions as a modulator of neurotransmission, smooth muscle contraction, and immune response in several systems of the human body, including the cardiovascular system. In the vasculature, four P1-receptors or adenosine receptors—A₁, A_2A, [...] Read more.

Adenosine is an adenine base purine with actions as a modulator of neurotransmission, smooth muscle contraction, and immune response in several systems of the human body, including the cardiovascular system. In the vasculature, four P1-receptors or adenosine receptors—A₁, A_2A, A_2B and A₃—have been identified. Adenosine receptors are membrane G-protein receptors that trigger their actions through several signaling pathways and present differential affinity requirements. Adenosine is an endogenous ligand whose extracellular levels can reach concentrations high enough to activate the adenosine receptors. This nucleoside is a product of enzymatic breakdown of extra and intracellular adenine nucleotides and also of S-adenosylhomocysteine. Adenosine availability is also dependent on the activity of nucleoside transporters (NTs). The interplay between NTs and adenosine receptors’ activities are debated and a particular attention is given to the paramount importance of the disruption of this interplay in vascular pathophysiology, namely in hypertension., The integration of important functional aspects of individual adenosine receptor pharmacology (such as in vasoconstriction/vasodilation) and morphological features (within the three vascular layers) in vessels will be discussed, hopefully clarifying the importance of adenosine receptors/NTs for modulating peripheral mesenteric vascular resistance. In recent years, an increase interest in purine physiology/pharmacology has led to the development of new ligands for adenosine receptors. Some of them have been patented as having promising therapeutic activities and some have been chosen to undergo on clinical trials. Increased levels of endogenous adenosine near a specific subtype can lead to its activation, constituting an indirect receptor targeting approach either by inhibition of NT or, alternatively, by increasing the activity of enzymes responsible for ATP breakdown. These findings highlight the putative role of adenosinergic players as attractive therapeutic targets for cardiovascular pathologies, namely hypertension, heart failure or stroke. Nevertheless, several aspects are still to be explored, creating new challenges to be addressed in future studies, particularly the development of strategies able to circumvent the predicted side effects of these therapies. Full article

(This article belongs to the Special Issue Adenosine Receptors)

16 pages, 5491 KiB

Open AccessReview

Sulfated Alginates as Heparin Analogues: A Review of Chemical and Functional Properties

by Øystein Arlov¹

and Gudmund Skjåk-Bræk^2,*

¹ Department of Biotechnology and Nanomedicine, SINTEF Materials and Chemistry, Richard Birkelands vei 3B, 7034 Trondheim, Norway

² Department of Biotechnology, Norwegian University of Science and Technology, Sem Sælands vei 6/8, 7034 Trondheim, Norway

Molecules 2017, 22(5), 778; https://doi.org/10.3390/molecules22050778 - 11 May 2017

Cited by 57 | Viewed by 9707

Abstract

Heparin is widely recognized for its potent anticoagulating effects, but has an additional wide range of biological properties due to its high negative charge and heterogeneous molecular structure. This heterogeneity has been one of the factors in motivating the exploration of functional analogues [...] Read more.

Heparin is widely recognized for its potent anticoagulating effects, but has an additional wide range of biological properties due to its high negative charge and heterogeneous molecular structure. This heterogeneity has been one of the factors in motivating the exploration of functional analogues with a more predictable modification pattern and monosaccharide sequence, that can aid in elucidating structure-function relationships and further be structurally customized to fine-tune physical and biological properties toward novel therapeutic applications and biomaterials. Alginates have been of great interest in biomedicine due to their inherent biocompatibility, gentle gelling conditions, and structural versatility from chemo-enzymatic engineering, but display limited interactions with cells and biomolecules that are characteristic of heparin and the other glycosaminoglycans (GAGs) of the extracellular environment. Here, we review the chemistry and physical and biological properties of sulfated alginates as structural and functional heparin analogues, and discuss how they may be utilized in applications where the use of heparin and other sulfated GAGs is challenging and limited. Full article

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

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54 pages, 17924 KiB

Open AccessReview

Hypervalent Iodine Reagents in High Valent Transition Metal Chemistry

by Felipe Cesar Sousa e Silva, Anthony F. Tierno and Sarah E. Wengryniuk^*

Department of Chemistry, Temple University, 1901 N. 13th St., Philadelphia, PA 19122, USA

Molecules 2017, 22(5), 780; https://doi.org/10.3390/molecules22050780 - 12 May 2017

Cited by 56 | Viewed by 15946

Abstract

Over the last 20 years, high valent metal complexes have evolved from mere curiosities to being at the forefront of modern catalytic method development. This approach has enabled transformations complimentary to those possible via traditional manifolds, most prominently carbon-heteroatom bond formation. Key to [...] Read more.

Over the last 20 years, high valent metal complexes have evolved from mere curiosities to being at the forefront of modern catalytic method development. This approach has enabled transformations complimentary to those possible via traditional manifolds, most prominently carbon-heteroatom bond formation. Key to the advancement of this chemistry has been the identification of oxidants that are capable of accessing these high oxidation state complexes. The oxidant has to be both powerful enough to achieve the desired oxidation as well as provide heteroatom ligands for transfer to the metal center; these heteroatoms are often subsequently transferred to the substrate via reductive elimination. Herein we will review the central role that hypervalent iodine reagents have played in this aspect, providing an ideal balance of versatile reactivity, heteroatom ligands, and mild reaction conditions. Furthermore, these reagents are environmentally benign, non-toxic, and relatively inexpensive compared to other inorganic oxidants. We will cover advancements in both catalysis and high valent complex isolation with a key focus on the subtle effects that oxidant choice can have on reaction outcome, as well as limitations of current reagents. Full article

(This article belongs to the Special Issue Women in Organic Chemistry)

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21 pages, 6698 KiB

Open AccessReview

Bioactive Natural Products of Marine Sponges from the Genus Hyrtios

by Nourhan Hisham Shady¹, Ebaa M. El-Hossary², Mostafa A. Fouad³, Tobias A. M. Gulder⁴, Mohamed Salah Kamel³ and Usama Ramadan Abdelmohsen^3,5,*

¹ Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, Universities Zone, P.O. Box 61111 New Minia City, Minia, Egypt

² National Centre for Radiation Research & Technology, Egyptian Atomic Energy Authority, Ahmed El-Zomor St. 3, El-Zohoor Dist., P.O. Box 29 Nasr City, Cairo, Egypt

³ Department of Pharmacognosy, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt

⁴ Department of Chemistry and Center for Integrated Protein Science Munich (CIPSM), Technische Universität München, Lichtenbergstraβe 4, 85748 Garching, Germany

⁵ Department of Botany II, Julius-von-Sachs Institute for Biological Sciences, University of Würzburg, Julius-von-Sachs-Platz 3, 97082 Würzburg, Germany

Molecules 2017, 22(5), 781; https://doi.org/10.3390/molecules22050781 - 11 May 2017

Cited by 47 | Viewed by 9888

Abstract

Marine sponges are known as a rich source for novel bioactive compounds with valuable pharmacological potential. One of the most predominant sponge genera is Hyrtios, reported to have various species such as Hyrtios erectus, Hyrtios reticulatus, Hyrtios gumminae, Hyrtios [...] Read more.

Marine sponges are known as a rich source for novel bioactive compounds with valuable pharmacological potential. One of the most predominant sponge genera is Hyrtios, reported to have various species such as Hyrtios erectus, Hyrtios reticulatus, Hyrtios gumminae, Hyrtios communis, and Hyrtios tubulatus and a number of undescribed species. Members of the genus Hyrtios are a rich source of natural products with diverse and valuable biological activities, represented by different chemical classes including alkaloids, sesterterpenes and sesquiterpenes. This review covers the literature until June 2016, providing a complete survey of all compounds isolated from the genus Hyrtios with their corresponding biological activities whenever applicable. Full article

(This article belongs to the Collection Bioactive Compounds)

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19 pages, 38110 KiB

Open AccessReview

Mesoporous Silica Nanoparticles as Carriers for Intracellular Delivery of Nucleic Acids and Subsequent Therapeutic Applications

by Wenzhang Cha^1,†, Rengen Fan^1,†, Yufeng Miao^2,†, Yong Zhou¹, Chenglin Qin¹, Xiangxiang Shan^3,*, Xinqiang Wan^4,* and Jinbo Li^5,*

¹ Department of General Surgery, Yancheng City No. 1 People’s Hospital, Yancheng 224001, China

² Department of Medical Oncology, Yancheng City No. 1 People’s Hospital, Yancheng 224001, China

³ Department of Gerontology, Yancheng City No. 1 People’s Hospital, Yancheng 224001, China

⁴ Department of Clinical Medicine, Nantong University Xinglin College, Nantong 226000, China

⁵ School of Chemistry and Chemical Engineering, Nanjing Unviersity, Nanjing 210023, China

^† These authors contributed equally to this work.

Molecules 2017, 22(5), 782; https://doi.org/10.3390/molecules22050782 - 11 May 2017

Cited by 61 | Viewed by 8773

Abstract

Nucleic acids, including DNA, microRNA (miRNA), small interfering RNA (siRNA), and antisense oligonucleotide (ASO), are powerful gene regulators, which have been demonstrated as promising drug candidates for therapeutic treatments. Nevertheless, poor cellular membrane permeability and serum stability have greatly hindered the applications of [...] Read more.

Nucleic acids, including DNA, microRNA (miRNA), small interfering RNA (siRNA), and antisense oligonucleotide (ASO), are powerful gene regulators, which have been demonstrated as promising drug candidates for therapeutic treatments. Nevertheless, poor cellular membrane permeability and serum stability have greatly hindered the applications of nucleic acids in biomedicine. To address these issues, associate carriers that can encapsulate and protect nucleic acids are urgently required. Mesoporous silica nanoparticles (MSNs or MSNPs), which are nanomaterials with excellent biocompatibility, large surface area for functionalization, and tunable pore size for encapsulating different cargos, are emerging as novel and ideal biomaterials for different biomedical applications. In this review paper, we focus on the applications of MSNs in nucleic acid delivery and nucleic acid-guided therapeutic treatments. General strategies for the preparation of nucleic acid-MSN complexes will be firstly introduced, followed by a summary of recent applications of MSNs in nucleic acid delivery and nucleic acid-guided therapeutics. Full article

(This article belongs to the Special Issue Mesoporous Silica in Biomedical Applications)

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16 pages, 2580 KiB

Open AccessReview

Photoactive Hybrid Catalysts Based on Natural and Synthetic Polymers: A Comparative Overview

by Juan Carlos Colmenares^* and Ewelina Kuna

Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland

Molecules 2017, 22(5), 790; https://doi.org/10.3390/molecules22050790 - 12 May 2017

Cited by 40 | Viewed by 10816

Abstract

In the present review, we would like to draw the reader’s attention to the polymer-based hybrid materials used in photocatalytic processes for efficient degradation of organic pollutants in water. These inorganic–organic materials exhibit unique physicochemical properties due to the synergistic effect originating from [...] Read more.

In the present review, we would like to draw the reader’s attention to the polymer-based hybrid materials used in photocatalytic processes for efficient degradation of organic pollutants in water. These inorganic–organic materials exhibit unique physicochemical properties due to the synergistic effect originating from the combination of individual elements, i.e., photosensitive metal oxides and polymeric supports. The possibility of merging the structural elements of hybrid materials allows for improving photocatalytic performance through (1) an increase in the light-harvesting ability; (2) a reduction in charge carrier recombination; and (3) prolongation of the photoelectron lifetime. Additionally, the great majority of polymer materials exhibit a high level of resistance against ultraviolet irradiation and improved corrosion resistance. Taking into account that the chemical and environmental stability of the hybrid catalyst depends, to a great extent, on the functional support, we highlight benefits and drawbacks of natural and synthetic polymer-based photocatalytic materials and pay special attention to the fact that the accessibility of synthetic polymeric materials derived from petroleum may be impeded due to decreasing amounts of crude oil. Thus, it is necessary to look for cheap and easily available raw materials like natural polymers that come from, for instance, lignocellulosic wastes or crustacean residues to meet the demand of the “plastic” market. Full article

(This article belongs to the Special Issue Photon-involving Purification of Water and Air)

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10 pages, 3614 KiB

Open AccessReview

Flexible Antibacterial Coatings

by Jindřich Musil

Department of Physics and NTIS Centre of Excellence, Faculty of Applied Sciences, University of West Bohemia, Univerzitní 22, CZ-306 14 Plzeň, Czech Republic

Molecules 2017, 22(5), 813; https://doi.org/10.3390/molecules22050813 - 16 May 2017

Cited by 27 | Viewed by 7723

Abstract

This article reviews the present state of the art in the field of flexible antibacterial coatings which efficiently kill bacteria on their surfaces. Coatings are formed using a reactive magnetron sputtering. The effect of the elemental composition and structure of the coating on [...] Read more.

This article reviews the present state of the art in the field of flexible antibacterial coatings which efficiently kill bacteria on their surfaces. Coatings are formed using a reactive magnetron sputtering. The effect of the elemental composition and structure of the coating on its antibacterial and mechanical properties is explained. The properties of Cr–Cu–O, Al–Cu–N, and Zr–Cu–N antibacterial coatings are used as examples and described in detail. The efficiency of killing of bacteria was tested for the Escherichia coli bacterium. The principle of the formation of thick, flexible antibacterial coatings which are resistant to cracking under bending is explained. It is shown that magnetron sputtering enables production of robust, several-micrometer thick, flexible antibacterial coatings for long-term use. The antibacterial coatings produced by magnetron sputtering present huge potential for many applications. Full article

(This article belongs to the Special Issue Antibacterial Materials and Coatings)

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14 pages, 569 KiB

Open AccessReview

Combining Pharmacological Countermeasures to Attenuate the Acute Radiation Syndrome—A Concise Review

by Michal Hofer^*, Zuzana Hoferová, Daniel Depeš and Martin Falk

Department of Cell Biology and Radiobiology, Institute of Biophysics, v.v.i., Czech Academy of Sciences, Královopolská 135, 61265 Brno, Czech Republic

Molecules 2017, 22(5), 834; https://doi.org/10.3390/molecules22050834 - 19 May 2017

Cited by 15 | Viewed by 5433

Abstract

The goal of combined pharmacological approaches in the treatment of the acute radiation syndrome (ARS) is to obtain an effective therapy producing a minimum of undesirable side effects. This review summarizes important data from studies evaluating the efficacy of combining radioprotective agents developed [...] Read more.

The goal of combined pharmacological approaches in the treatment of the acute radiation syndrome (ARS) is to obtain an effective therapy producing a minimum of undesirable side effects. This review summarizes important data from studies evaluating the efficacy of combining radioprotective agents developed for administration prior to irradiation and therapeutic agents administered in a post-irradiation treatment regimen. Many of the evaluated results show additivity, or even synergism, of the combined treatments in comparison with the effects of the individual component administrations. It can be deduced from these findings that the research in which combined treatments with radioprotectors/radiomitigators are explored, tested, and evaluated is well-founded. The requirement for studies highly emphasizing the need to minimize undesirable side effects of the radioprotective/radiomitigating therapies is stressed. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 2787 KiB

Open AccessReview

Electrophilic Selenium Catalysis with Electrophilic N-F Reagents as the Oxidants

by Ruizhi Guo, Lihao Liao and Xiaodan Zhao^*

Institute of Organic Chemistry & MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, China

Molecules 2017, 22(5), 835; https://doi.org/10.3390/molecules22050835 - 19 May 2017

Cited by 82 | Viewed by 9421

Abstract

A suitable oxidative system is crucial to electrophilic selenium catalysis (ESC). This short review offers the overview of recent development in ESC with electrophilic N-F reagents as the oxidants. Several highly selective transformations of alkenes such as allylic or vinylic imidation, pyridination, syn [...] Read more.

A suitable oxidative system is crucial to electrophilic selenium catalysis (ESC). This short review offers the overview of recent development in ESC with electrophilic N-F reagents as the oxidants. Several highly selective transformations of alkenes such as allylic or vinylic imidation, pyridination, syn-dichlorination, oxidative cyclization and asymmetric cyclization have been described. Full article

(This article belongs to the Special Issue Celebrating Two Centuries of Research in Selenium Chemistry: State of the Art and New Prospectives)

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20 pages, 4294 KiB

Open AccessReview

The Impact of Halloysite on the Thermo-Mechanical Properties of Polymer Composites

by Tayser Sumer Gaaz^1,2,*, Abu Bakar Sulong^1,*, Abdul Amir H. Kadhum³, Ahmed A. Al-Amiery³

, Mohamed H. Nassir⁴ and Ahed Hameed Jaaz⁵

¹ Department of Mechanical & Materials Engineering, Faculty of Engineering & Built Environment, Universiti Kebangsaan Malaysia, Bangi, Selangor 43600, Malaysia

² Department of Machinery Equipment Engineering Techniques, Technical College Al-Musaib, Al-Furat Al-Awsat Technical University, Al-Musaib, Babil 51009, Iraq

³ Department of Chemical & Process Engineering, Faculty of Engineering & Built Environment, Universiti Kebangsaan Malaysia, Bangi, Selangor 43600, Malaysia

⁴ Program of Chemical Engineering, Taylor′s University-Lakeside Campus, Subang Jaya, Selangor 47500, Malaysia

⁵ Solar Energy Research Institute (SERI), Universiti Kebangsaan Malaysia, Bangi, Selangor 43600, Malaysia

Molecules 2017, 22(5), 838; https://doi.org/10.3390/molecules22050838 - 20 May 2017

Cited by 103 | Viewed by 10382

Abstract

Nanotubular clay minerals, composed of aluminosilicate naturally structured in layers known as halloysite nanotubes (HNTs), have a significant reinforcing impact on polymer matrixes. HNTs have broad applications in biomedical applications, the medicine sector, implant alloys with corrosion protection and manipulated transportation of medicines. [...] Read more.

Nanotubular clay minerals, composed of aluminosilicate naturally structured in layers known as halloysite nanotubes (HNTs), have a significant reinforcing impact on polymer matrixes. HNTs have broad applications in biomedical applications, the medicine sector, implant alloys with corrosion protection and manipulated transportation of medicines. In polymer engineering, different research studies utilize HNTs that exhibit a beneficial enhancement in the properties of polymer-based nanocomposites. The dispersion of HNTs is improved as a result of pre-treating HNTs with acids. The HNTs’ percentage additive up to 7% shows the highest improvement of tensile strength. The degradation of the polymer can be also significantly improved by doping a low percentage of HNTs. Both the mechanical and thermal properties of polymers were remarkably improved when mixed with HNTs. The effects of HNTs on the mechanical and thermal properties of polymers, such as ultimate strength, elastic modulus, impact strength and thermal stability, are emphasized in this study. Full article

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19 pages, 254 KiB

Open AccessReview

Antidiabetic Effects of Tea

by Qiu-Yue Fu^1,†, Qing-Sheng Li^1,†, Xiao-Ming Lin¹, Ru-Ying Qiao¹, Rui Yang¹, Xu-Min Li¹, Zhan-Bo Dong², Li-Ping Xiang³, Xin-Qiang Zheng¹

, Jian-Liang Lu¹, Cong-Bo Yuan⁴, Jian-Hui Ye^1,* and Yue-Rong Liang^1,*

¹ Tea Research Institute, Zhejiang University, Hangzhou 310058, China

² Wenzhou Vocational College of Science and Technology, Wenzhou 325035, China

³ National Tea and Tea product Quality Supervision and Inspection Center (Guizhou), Zunyi 563100, China

⁴ Yuyuanchun Tea Limited, Jufeng Town, Rizhao 276812, China

^† These authors contributed equally to this work.

Molecules 2017, 22(5), 849; https://doi.org/10.3390/molecules22050849 - 20 May 2017

Cited by 100 | Viewed by 15038

Abstract

Diabetes mellitus (DM) is a chronic endocrine disease resulted from insulin secretory defect or insulin resistance and it is a leading cause of death around the world. The care of DM patients consumes a huge budget due to the high frequency of consultations [...] Read more.

Diabetes mellitus (DM) is a chronic endocrine disease resulted from insulin secretory defect or insulin resistance and it is a leading cause of death around the world. The care of DM patients consumes a huge budget due to the high frequency of consultations and long hospitalizations, making DM a serious threat to both human health and global economies. Tea contains abundant polyphenols and caffeine which showed antidiabetic activity, so the development of antidiabetic medications from tea and its extracts is increasingly receiving attention. However, the results claiming an association between tea consumption and reduced DM risk are inconsistent. The advances in the epidemiologic evidence and the underlying antidiabetic mechanisms of tea are reviewed in this paper. The inconsistent results and the possible causes behind them are also discussed. Full article

(This article belongs to the Special Issue Plant Polyphenols as Potential Therapeutic Agents for Diabetes and Obesity)

16 pages, 3619 KiB

Open AccessReview

Applications of Gold Nanoparticles in Nanomedicine: Recent Advances in Vaccines

by Sónia Alexandra Correia Carabineiro^†

¹ Laboratório de Catálise e Materiais (LCM), Laboratório Associado LSRE-LCM, Faculdade de Engenharia, Universidade do Porto, 4200-465 Porto, Portugal

^† Dedicated to the memory of my friend and colleague Dr. Andreea Catalina Gluhoi, a female gold researcher, who passed away too soon.

Molecules 2017, 22(5), 857; https://doi.org/10.3390/molecules22050857 - 22 May 2017

Cited by 115 | Viewed by 13667

Abstract

Nowadays, gold is used in (nano-)medicine, usually in the form of nanoparticles, due to the solid proofs given of its therapeutic effects on several diseases. Gold also plays an important role in the vaccine field as an adjuvant and a carrier, reducing toxicity, [...] Read more.

Nowadays, gold is used in (nano-)medicine, usually in the form of nanoparticles, due to the solid proofs given of its therapeutic effects on several diseases. Gold also plays an important role in the vaccine field as an adjuvant and a carrier, reducing toxicity, enhancing immunogenic activity, and providing stability in storage. An even brighter golden future is expected for gold applications in this area. Full article

(This article belongs to the Special Issue Women in Organic Chemistry)

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Molecules, Volume 22, Issue 5 (May 2017) – 174 articles

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