Molecules

13 pages, 4507 KiB

Open AccessArticle

Optimization of Antifungal Extracts from Ficus hirta Fruits Using Response Surface Methodology and Antifungal Activity Tests

by Chuying Chen, Chunpeng Wan

, Xuan Peng, Yuhuan Chen, Ming Chen and Jinyin Chen^*

Jiangxi Key Laboratory for Postharvest Technology and Nondestructive Testing of Fruits & Vegetables, College of Agronomy, Jiangxi Agricultural University, Nanchang 330045, China

Molecules 2015, 20(11), 19647-19659; https://doi.org/10.3390/molecules201119648 - 29 Oct 2015

Cited by 21 | Viewed by 5828

Abstract

The fruits of Ficus hirta (FH) display strong antifungal activity against Penicillium italicum and Penicillium digitatum. In order to optimize the extraction conditions of antifungal extracts from FH fruit, various extraction parameters, such as ethanol concentration, extraction time, solvent to solid ratio [...] Read more.

The fruits of Ficus hirta (FH) display strong antifungal activity against Penicillium italicum and Penicillium digitatum. In order to optimize the extraction conditions of antifungal extracts from FH fruit, various extraction parameters, such as ethanol concentration, extraction time, solvent to solid ratio and temperature, were chosen to identify their effects on the diameters of inhibition zones (DIZs) against these two Penicillium molds. Response surface methodology (RSM) was applied to obtain the optimal combination of these parameters. Results showed that the optimal extraction parameters for maximum antifungal activity were: 90% (v/v) ethanol concentration, 65 min extraction time, 31 mL/g solvent to solid ratio and 51 °C temperature. Under the abovementioned extraction conditions, the experimental DIZs values obtained experimentally were 57.17 ± 0.75 and 39.33 ± 0.82 mm, which were very close to the values of 57.26 and 39.29 mm predicted by the model. Further, nine kinds of phytopathogens were tested in vitro to explore the antifungal activity of the FH extracts. It was found for the first time that the FH extracts showed significant inhibition on the growth of P. italicum, A. citri, P. vexans, P. cytosporella and P. digitatum. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 341 KiB

Open AccessArticle

Comparative Anticonvulsant Study of Epoxycarvone Stereoisomers

by Paula Regina Rodrigues Salgado¹, Diogo Vilar Da Fonsêca¹, Renan Marinho Braga¹, Cynthia Germoglio Farias De Melo¹, Luciana Nalone Andrade², Reinaldo Nóbrega De Almeida^1,3 and Damião Pergentino De Sousa^1,4,*

¹ Instituto de Pesquisa em Fármacos e Medicamentos, Universidade Federal da Paraíba, CP 5009, João Pessoa, CEP 58051-900, PB, Brazil

² Departamento de Farmácia, Universidade Federal de Sergipe, São Cristóvão-SE, CEP 49100-000, Brazil

³ Departamento de Fisiologia e Patologia, Universidade Federal da Paraíba, CP 5009, João Pessoa, CEP 58051-900, PB, Brazil

⁴ Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, CP 5009, João Pessoa, CEP 58051-900, PB, Brazil

Molecules 2015, 20(11), 19660-19673; https://doi.org/10.3390/molecules201119649 - 29 Oct 2015

Cited by 19 | Viewed by 6464

Abstract

Stereoisomers of the monoterpene epoxycarvone (EC), namely (+)-cis-EC, (−)-cis-EC, (+)-trans-EC, and (−)-trans-EC, were comparatively evaluated for anticonvulsant activity in specific methodologies. In the pentylenetetrazole (PTZ)-induced anticonvulsant test, all of the stereoisomers (at 300 mg/kg) [...] Read more.

Stereoisomers of the monoterpene epoxycarvone (EC), namely (+)-cis-EC, (−)-cis-EC, (+)-trans-EC, and (−)-trans-EC, were comparatively evaluated for anticonvulsant activity in specific methodologies. In the pentylenetetrazole (PTZ)-induced anticonvulsant test, all of the stereoisomers (at 300 mg/kg) increased the latency to seizure onset, and afforded 100% protection against the death of the animals. In the maximal electroshock-induced seizures (MES) test, prevention of tonic seizures was also verified for all of the isomers tested. However, the isomeric forms (+) and (−)-trans-EC showed 25% and 12.5% inhibition of convulsions, respectively. In the pilocarpine-induced seizures test, all stereoisomers demonstrated an anticonvulsant profile, yet the stereoisomers (+) and (−)-trans-EC (at 300 mg/kg) showed a more pronounced effect. A strychnine-induced anticonvulsant test was performed, and none of the stereoisomers significantly increased the latency to onset of convulsions; the stereoisomers probably do not act in this pathway. However, the stereoisomers (+)-cis-EC and (+)-trans-EC greatly increased the latency to death of the animals, thus presenting some protection. The four EC stereoisomers show promise for anticonvulsant activity, an effect emphasized in the isomers (+)-cis-EC, (+)-trans-EC, and (−)-trans-EC for certain parameters of the tested methodologies. These results serve as support for further research and development of antiepileptic drugs from monoterpenes. Full article

(This article belongs to the Section Natural Products Chemistry)

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16 pages, 3570 KiB

Open AccessArticle

X-ray Crystallography, DFT Calculations and Molecular Docking of Indole-Arylpiperazine Derivatives as α_1A-Adrenoceptor Antagonists

by Wei Xu¹, Jun-Jun Huang¹, Bin-Hao Shao¹, Xing-Jie Xu¹, Ren-Wang Jiang² and Mu Yuan^1,*

¹ Pharmaceutical Research Center, Guangzhou Medical University, 195# Dongfengxi Road, Guangzhou 510182, China

² School of Pharmaceutical Sciences, Jinan University, Guangzhou 510632, China

Molecules 2015, 20(11), 19674-19689; https://doi.org/10.3390/molecules201119651 - 30 Oct 2015

Cited by 7 | Viewed by 6958

Abstract

Indole-arylpiperazine derivatives have exhibited good selectivity for the α_1A-adrenoceptor, but the structure-activity-binding mechanism relationship remains unclear. In the current study, three compounds (1, 2 and 3) were investigated through single-crystal X-ray diffraction analysis, density functional theory (DFT) calculations [...] Read more.

Indole-arylpiperazine derivatives have exhibited good selectivity for the α_1A-adrenoceptor, but the structure-activity-binding mechanism relationship remains unclear. In the current study, three compounds (1, 2 and 3) were investigated through single-crystal X-ray diffraction analysis, density functional theory (DFT) calculations and molecular docking using a homology model of the α_1A receptor. Compounds 1 and 3 form H-bonds networks to stabilize their three-dimensional structures, while C–H···π interactions play a significant role in the packing of 2. Based on DFT-optimized conformations, the HOMO-LUMO energy gaps and molecular electrostatic potential (MEP) were theoretically calculated at the B3LYP/6-311G (d, p) level of theory. Chemical reactivity increases in the order of 3 < 2 < 1, and the maximum positive region of the MEP maps is mainly localized over the NH group. The binding mechanisms of ligand-α_1A-adrenoceptor complexes were illustrated by molecular docking. Binding to Gln177 of the second extracellular loop region via hydrogen bonds is likely to be essential for α_1A-selective antagonists. The present work sheds light on the studies of structure-activity-binding mechanism and aids in the design of α_1A antagonists with high selectivity. Full article

(This article belongs to the Section Medicinal Chemistry)

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9 pages, 2155 KiB

Open AccessArticle

Tetracycline-Containing MCM-41 Mesoporous Silica Nanoparticles for the Treatment of Escherichia coli

by Bhuvaneswari Koneru^1,†, Yi Shi^1,†, Yu-Chieh Wang¹, Sai H. Chavala², Michael L. Miller³, Brittany Holbert¹, Maricar Conson¹, Aiguo Ni⁴ and Anthony J. Di Pasqua^1,*

¹ Department of Pharmaceutical Sciences, University of North Texas System College of Pharmacy, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107, USA

² North Texas Eye Research Institute, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107, USA

³ Department of Chemistry, Creighton University, 2500 California Plaza, Omaha, NE 68178, USA

⁴ Department of Cell Biology and Immunology, Graduate School of Biomedical Sciences, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107, USA

^† These authors contributed equally to this work

Molecules 2015, 20(11), 19690-19698; https://doi.org/10.3390/molecules201119650 - 30 Oct 2015

Cited by 50 | Viewed by 9602

Abstract

Tetracycline (TC) is a well-known broad spectrum antibiotic, which is effective against many Gram positive and Gram negative bacteria. Controlled release nanoparticle formulations of TC have been reported, and could be beneficial for application in the treatment of periodontitis and dental bone infections. [...] Read more.

Tetracycline (TC) is a well-known broad spectrum antibiotic, which is effective against many Gram positive and Gram negative bacteria. Controlled release nanoparticle formulations of TC have been reported, and could be beneficial for application in the treatment of periodontitis and dental bone infections. Furthermore, TC-controlled transcriptional regulation systems (Tet-on and Tet-off) are useful for controlling transgene expression in vitro and in vivo for biomedical research purposes; controlled TC release systems could be useful here, as well. Mesoporous silica nanomaterials (MSNs) are widely studied for drug delivery applications; Mobile crystalline material 41 (MCM-41), a type of MSN, has a mesoporous structure with pores forming channels in a hexagonal fashion. We prepared 41 ± 4 and 406 ± 55 nm MCM-41 mesoporous silica nanoparticles and loaded TC for controlled dug release; TC content in the TC-MCM-41 nanoparticles was 18.7% and 17.7% w/w, respectively. Release of TC from TC-MCM-41 nanoparticles was then measured in phosphate-buffered saline (PBS), pH 7.2, at 37 °C over a period of 5 h. Most antibiotic was released from both over this observation period; however, the majority of TC was released over the first hour. Efficacy of the TC-MCM-41 nanoparticles was then shown to be superior to free TC against Escherichia coli (E. coli) in culture over a 24 h period, while blank nanoparticles had no effect. Full article

(This article belongs to the Collection Nanomedicine)

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20 pages, 2958 KiB

Open AccessArticle

Anticancer and Antibacterial Activity Studies of Gold(I)-Alkynyl Chromones

by Paweł Hikisz¹, Łukasz Szczupak², Aneta Koceva-Chyła¹, Adam Guśpiel³, Luciano Oehninger⁴, Ingo Ott⁴, Bruno Therrien⁵, Jolanta Solecka³ and Konrad Kowalski^2,*

¹ Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Łód´z, Pomorska 141/143, Łód´z PL-90236, Poland

² Department of Organic Chemistry, Faculty of Chemistry, University of Łód´z, Tamka 12, Łód´z PL-91403, Poland

³ Laboratory of Biologically Active Compounds, National Institute of Public Health-National Institute of Hygiene, Chocimska 24, Warsaw PL-00791, Poland

⁴ Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Beethovenstr. 55, Braunschweig D-38106, Germany

⁵ Institute of Chemistry, Faculty of Science, University of Neuchatel, Avenue de Bellevaux 51, Neuchatel CH-2000, Switzerland

Molecules 2015, 20(11), 19699-19718; https://doi.org/10.3390/molecules201119647 - 30 Oct 2015

Cited by 50 | Viewed by 9196

Abstract

Three gold(I) complexes of alkynyl chromones were synthesized and characterized. The single-crystal X-ray structure analysis of a dinuclear compound and of a flavone derivative exhibit a typical d10 gold(I)-alkynyl linear arrangement. All complexes were evaluated as anticancer and antibacterial agents against four human [...] Read more.

Three gold(I) complexes of alkynyl chromones were synthesized and characterized. The single-crystal X-ray structure analysis of a dinuclear compound and of a flavone derivative exhibit a typical d10 gold(I)-alkynyl linear arrangement. All complexes were evaluated as anticancer and antibacterial agents against four human cancer cell lines and four pathogenic bacterial strains. All compounds show antiproliferative activity at lower micromolar range concentrations. Complex 4 showed a broad activity profile, being more active than the reference drug auranofin against HepG2, MCF-7 and CCRF-CEM cancer cells. The cellular uptake into MCF-7 cells of the investigated complexes was measured by atomic absorption spectroscopy (AAS). These measurements showed a positive correlation between an increased cellular gold content and the incubation time of the complexes. Unexpectedly an opposite effect was observed for the most active compound. Biological assays revealed various molecular mechanisms for these compounds, comprising: (i) thioredoxin reductase (TrxR) inhibition, (ii) caspases-9 and -3 activation; (iii) DNA damaging activity and (iv) cell cycle disturbance. The gold(I) complexes were also bactericidal against Gram-positive methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) bacterial strains, while showing no activity against the Gram-negative Escherichia coli bacterial strain. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

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16 pages, 2290 KiB

Open AccessArticle

Chemotaxonomic Metabolite Profiling of 62 Indigenous Plant Species and Its Correlation with Bioactivities

by Sarah Lee^1,†, Dong-Gu Oh^2,†, Sunmin Lee², Ga Ryun Kim¹, Jong Seok Lee¹, Youn Kyoung Son¹, Chang-Hwan Bae¹, Joohong Yeo¹ and Choong Hwan Lee^2,*

¹ National Institute of Biological Resources, Environmental Research Complex, Incheon 404-708, Korea

² Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Korea

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 19719-19734; https://doi.org/10.3390/molecules201119652 - 2 Nov 2015

Cited by 32 | Viewed by 7556

Abstract

Chemotaxonomic metabolite profiling of 62 indigenous Korean plant species was performed by ultrahigh performance liquid chromatography (UHPLC)-linear trap quadrupole-ion trap (LTQ-IT) mass spectrometry/mass spectrometry (MS/MS) combined with multivariate statistical analysis. In partial least squares discriminant analysis (PLS-DA), the 62 species clustered depending on [...] Read more.

Chemotaxonomic metabolite profiling of 62 indigenous Korean plant species was performed by ultrahigh performance liquid chromatography (UHPLC)-linear trap quadrupole-ion trap (LTQ-IT) mass spectrometry/mass spectrometry (MS/MS) combined with multivariate statistical analysis. In partial least squares discriminant analysis (PLS-DA), the 62 species clustered depending on their phylogenetic family, in particular, Aceraceae, Betulaceae, and Fagaceae were distinguished from Rosaceae, Fabaceae, and Asteraceae. Quinic acid, gallic acid, quercetin, quercetin derivatives, kaempferol, and kaempferol derivatives were identified as family-specific metabolites, and were found in relatively high concentrations in Aceraceae, Betulaceae, and Fagaceae. Fagaceae and Asteraceae were selected based on results of PLS-DA and bioactivities to determine the correlation between metabolic differences among plant families and bioactivities. Quinic acid, quercetin, kaempferol, quercetin derivatives, and kaempferol derivatives were found in higher concentrations in Fagaceae than in Asteraceae, and were positively correlated with antioxidant and tyrosinase inhibition activities. These results suggest that metabolite profiling was a useful tool for finding the different metabolic states of each plant family and understanding the correlation between metabolites and bioactivities in accordance with plant family. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 3279 KiB

Open AccessArticle

Drug Discovery of Host CLK1 Inhibitors for Influenza Treatment

by Mian Zu^1,2,†, Chao Li^1,†, Jian-Song Fang¹, Wen-Wen Lian¹, Ai-Lin Liu^1,3,4,*, Li-Shu Zheng^5,* and Guan-Hua Du^1,3,4,*

¹ Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

² CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China

³ Beijing Key Laboratory of Drug Target Research and New Drug Screening, Beijing 100050, China

⁴ State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing 100050, China

⁵ National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 19735-19747; https://doi.org/10.3390/molecules201119653 - 2 Nov 2015

Cited by 29 | Viewed by 7868

Abstract

The rapid evolution of influenza virus makes antiviral drugs less effective, which is considered to be a major bottleneck in antiviral therapy. The key proteins in the host cells, which are related with the replication cycle of influenza virus, are regarded as potential [...] Read more.

The rapid evolution of influenza virus makes antiviral drugs less effective, which is considered to be a major bottleneck in antiviral therapy. The key proteins in the host cells, which are related with the replication cycle of influenza virus, are regarded as potential drug targets due to their distinct advantage of lack of evolution and drug resistance. Cdc2-like kinase 1 (CLK1) in the host cells is responsible for alternative splicing of the M2 gene of influenza virus during influenza infection and replication. In this study, we carried out baculovirus-mediated expression and purification of CLK1 and established a reliable screening assay for CLK1 inhibitors. After a virtual screening of CLK1 inhibitors was performed, the activities of the selected compounds were evaluated. Finally, several compounds with strong inhibitory activity against CLK1 were discovered and their in vitro anti-influenza virus activities were validated using a cytopathic effect (CPE) reduction assay. The assay results showed that clypearin, corilagin, and pinosylvine were the most potential anti-influenza virus compounds as CLK1 inhibitors among the compounds tested. These findings will provide important information for new drug design and development in influenza treatment, and CLK1 may be a potent drug target for anti-influenza drug screening and discovery. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 3569 KiB

Open AccessArticle

Shuidouchi (Fermented Soybean) Fermented in Different Vessels Attenuates HCl/Ethanol-Induced Gastric Mucosal Injury

by Huayi Suo^1,2,†, Xia Feng^3,4,†, Kai Zhu^3,4,†, Cun Wang^3,4, Xin Zhao^3,4,*

and Jianquan Kan^1,2,*

¹ College of Food Science, Southwest University, Chongqing 400715, China

² Chongqing Engineering Research Center of Regional Food, Chongqing 400715, China

³ Department of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, China

⁴ Chongqing Collaborative Innovation Center of Functional Food, Chongqing University of Education, Chongqing 400067, China

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 19748-19763; https://doi.org/10.3390/molecules201119654 - 2 Nov 2015

Cited by 30 | Viewed by 6895

Abstract

Shuidouchi (Natto) is a fermented soy product showing in vivo gastric injury preventive effects. The treatment effects of Shuidouchi fermented in different vessels on HCl/ethanol-induced gastric mucosal injury mice through their antioxidant effect was determined. Shuidouchi contained isoflavones (daidzein and genistein), and GVFS [...] Read more.

Shuidouchi (Natto) is a fermented soy product showing in vivo gastric injury preventive effects. The treatment effects of Shuidouchi fermented in different vessels on HCl/ethanol-induced gastric mucosal injury mice through their antioxidant effect was determined. Shuidouchi contained isoflavones (daidzein and genistein), and GVFS (glass vessel fermented Shuidouchi) had the highest isoflavone levels among Shuidouchi samples fermented in different vessels. After treatment with GVFS, the gastric mucosal injury was reduced as compared to the control mice. The gastric secretion volume (0.47 mL) and pH of gastric juice (3.1) of GVFS treated gastric mucosal injury mice were close to those of ranitidine-treated mice and normal mice. Shuidouchi could decrease serum motilin (MTL), gastrin (Gas) level and increase somatostatin (SS), vasoactive intestinal peptide (VIP) level, and GVFS showed the strongest effects. GVFS showed lower IL-6, IL-12, TNF-α and IFN-γ cytokine levels than other vessel fermented Shuidouchi samples, and these levels were higher than those of ranitidine-treated mice and normal mice. GVFS also had higher superoxide dismutase (SOD), nitric oxide (NO) and malonaldehyde (MDA) contents in gastric tissues than other Shuidouchi samples. Shuidouchi could raise IκB-α, EGF, EGFR, nNOS, eNOS, Mn-SOD, Gu/Zn-SOD, CAT mRNA expressions and reduce NF-κB, COX-2, iNOS expressions as compared to the control mice. GVFS showed the best treatment effects for gastric mucosal injuries, suggesting that glass vessels could be used for Shuidouchi fermentation in functional food manufacturing. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 1057 KiB

Open AccessArticle

Optimization of Extraction Condition of Bee Pollen Using Response Surface Methodology: Correlation between Anti-Melanogenesis, Antioxidant Activity, and Phenolic Content

by Seon Beom Kim¹, Yang Hee Jo¹, Qing Liu¹, Jong Hoon Ahn¹, In Pyo Hong², Sang Mi Han², Bang Yeon Hwang¹ and Mi Kyeong Lee^1,*

¹ College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28644, Korea

² National Academy of Agricultural Science, Rural Development Administration, Jeonju, Chonbuk 54875, Korea

Molecules 2015, 20(11), 19764-19774; https://doi.org/10.3390/molecules201119656 - 2 Nov 2015

Cited by 41 | Viewed by 8358

Abstract

Bee pollen is flower pollen with nectar and salivary substances of bees and rich in essential components. Bee pollen showed antioxidant and tyrosinase inhibitory activity in our assay system. To maximize the antioxidant and tyrosinase inhibitory activity of bee pollen, extraction conditions, such [...] Read more.

Bee pollen is flower pollen with nectar and salivary substances of bees and rich in essential components. Bee pollen showed antioxidant and tyrosinase inhibitory activity in our assay system. To maximize the antioxidant and tyrosinase inhibitory activity of bee pollen, extraction conditions, such as extraction solvent, extraction time, and extraction temperature, were optimized using response surface methodology. Regression analysis showed a good fit of this model and yielded the second-order polynomial regression for tyrosinase inhibition and antioxidant activity. Among the extraction variables, extraction solvent greatly affected the activity. The optimal condition was determined as EtOAc concentration in MeOH, 69.6%; temperature, 10.0 °C; and extraction time, 24.2 h, and the tyrosinase inhibitory and antioxidant activity under optimal condition were found to be 57.9% and 49.3%, respectively. Further analysis showed the close correlation between activities and phenolic content, which suggested phenolic compounds are active constituents of bee pollen for tyrosinase inhibition and antioxidant activity. Taken together, these results provide useful information about bee pollen as cosmetic therapeutics to reduce oxidative stress and hyperpigmentation. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 2664 KiB

Open AccessReview

The Phe-Phe Motif for Peptide Self-Assembly in Nanomedicine

by Silvia Marchesan^1,*

, Attilio V. Vargiu² and Katie E. Styan³

¹ Chemical and Pharmaceutical Sciences Department, University of Trieste, Via L. Giorgieri 1, Trieste 34127, Italy

² Department of Physics, University of Cagliari, Cittadella Universitaria S.P. Monserrato-Sestu Km. 0.700, Monserrato 09042, Italy

³ CSIRO Manufacturing, Bayview Ave Clayton, VIC 3168, Australia

Molecules 2015, 20(11), 19775-19788; https://doi.org/10.3390/molecules201119658 - 3 Nov 2015

Cited by 141 | Viewed by 18201

Abstract

Since its discovery, the Phe-Phe motif has gained in popularity as a minimalist building block to drive the self-assembly of short peptides and their analogues into nanostructures and hydrogels. Molecules based on the Phe-Phe motif have found a range of applications in nanomedicine, [...] Read more.

Since its discovery, the Phe-Phe motif has gained in popularity as a minimalist building block to drive the self-assembly of short peptides and their analogues into nanostructures and hydrogels. Molecules based on the Phe-Phe motif have found a range of applications in nanomedicine, from drug delivery and biomaterials to new therapeutic paradigms. Here we discuss the various production methods for this class of compounds, and the characterization, nanomorphologies, and application of their self-assembled nanostructures. We include the most recent findings on their remarkable properties, which hold substantial promise for the creation of the next generation nanomedicines. Full article

(This article belongs to the Collection Nanomedicine)

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16 pages, 2019 KiB

Open AccessArticle

Antihypertensive Effects of Artemisia scoparia Waldst in Spontaneously Hypertensive Rats and Identification of Angiotensin I Converting Enzyme Inhibitors

by Jeong-Yong Cho^1,†, Kyung-Hee Park^1,†, Do Young Hwang¹, Saoraya Chanmuang¹, Lily Jaiswal¹, Yang-Kyun Park¹, Sun-Young Park¹, So-Young Kim², Haeng-Ran Kim², Jae-Hak Moon³ and Kyung-Sik Ham^1,*

¹ Department of Food Biotechnology and Solar Salt Research Center, Mokpo National University, Jeonnam 534-729, Korea

² Division of Functional Food & Nutrition, National Academy of Agricultural Sciences, Rural Development Administration (RDA), Jeonbuk 560-500, Korea

³ Department of Food Science & Technology, and Functional Food Research Center, Chonnam National University, Gwangju 500-757, Korea

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 19789-19804; https://doi.org/10.3390/molecules201119657 - 3 Nov 2015

Cited by 31 | Viewed by 8534

Abstract

We investigated the antihypertensive effects of Artemisia scoparia (AS) in spontaneously hypertensive rats (SHR). The rats were fed diets containing 2% (w/w) hot water extracts of AS aerial parts for 6 weeks. The AS group had significantly lower systolic [...] Read more.

We investigated the antihypertensive effects of Artemisia scoparia (AS) in spontaneously hypertensive rats (SHR). The rats were fed diets containing 2% (w/w) hot water extracts of AS aerial parts for 6 weeks. The AS group had significantly lower systolic and diastolic blood pressure levels than the control group. The AS group also had lower angiotensin I converting enzyme (ACE) activity and angiotensin II content in serum compared to the control group. The AS group showed higher vascular endothelial growth factor and lower ras homolog gene family member A expression levels in kidney compared to the control group. The AS group had significantly lower levels of plasma lipid oxidation and protein carbonyls than the control group. One new and six known compounds were isolated from AS by guided purification. The new compound was determined to be 4′-O-β-D-glucopyranoyl (E)-4-hydroxy-3-methylbut-2-enyl benzoate, based on its nuclear magnetic resonance and electrospray ionization-mass spectroscopy data. Full article

(This article belongs to the Collection Bioactive Compounds)

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18 pages, 841 KiB

Open AccessArticle

Synthesis, Characterization and Biological Evaluation of Some Quinoxaline Derivatives: A Promising and Potent New Class of Antitumor and Antimicrobial Agents

by Aisha R. Al-Marhabi^1,2, Hebat-Allah S. Abbas^2,3,* and Yousry A. Ammar⁴

¹ Department of Chemistry, University College in Qunfudah, Umm Al Qura University, Qunfudah 21955, Saudi Arabia

² Department of Chemistry, Faculty of Science, King Khalid University, Abha 9004, Saudi Arabia

³ Department of Photochemistry, National Research Centre, Dokki 12622, Egypt

⁴ Department of Chemistry, Faculty of Science, Al-Azhar University, Cairo 11884, Egypt

Molecules 2015, 20(11), 19805-19822; https://doi.org/10.3390/molecules201119655 - 3 Nov 2015

Cited by 43 | Viewed by 7442

Abstract

In continuation of our endeavor towards the development of potent and effective anticancer and antimicrobial agents; the present work deals with the synthesis of some novel tetrazolo[1,5-a]quinoxalines, N-pyrazoloquinoxalines, the corresponding Schiff bases, 1,2,4-triazinoquinoxalines and 1,2,4-triazoloquinoxalines. These compounds were synthesized via [...] Read more.

In continuation of our endeavor towards the development of potent and effective anticancer and antimicrobial agents; the present work deals with the synthesis of some novel tetrazolo[1,5-a]quinoxalines, N-pyrazoloquinoxalines, the corresponding Schiff bases, 1,2,4-triazinoquinoxalines and 1,2,4-triazoloquinoxalines. These compounds were synthesized via the reaction of the key intermediate hydrazinoquinoxalines with various reagents and evaluated for anticancer and antimicrobial activity. The results indicated that tetrazolo[1,5-a]quinoxaline derivatives showed the best result, with the highest inhibitory effects towards the three tested tumor cell lines, which were higher than that of the reference doxorubicin and these compounds were non-cytotoxic to normal cells (IC₅₀ values > 100 μg/mL). Also, most of synthesized compounds exhibited the highest degrees of inhibition against the tested strains of Gram positive and negative bacteria, so tetrazolo[1,5-a]quinoxaline derivatives show dual activity as anticancer and antimicrobial agents. Full article

(This article belongs to the Section Bioorganic Chemistry)

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14 pages, 3809 KiB

Open AccessArticle

Anti-Inflammatory Activity Comparison among Scropoliosides—Catalpol Derivatives with 6-O-Substituted Cinnamyl Moieties

by Tiantian Zhu^1,2,†, Liuqiang Zhang^2,†, Shuang Ling¹, Fei Qian^1,2, Yiming Li^2,* and Jin-Wen Xu^1,*

¹ Murad Research Institute for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine

² School of Pharmacy, Shanghai University of Traditional Chinese Medicine

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 19823-19836; https://doi.org/10.3390/molecules201119659 - 3 Nov 2015

Cited by 20 | Viewed by 6515

Abstract

We have previously shown that scropolioside B has higher anti-inflammatory activity than catalpol does after the inhibition of nuclear factor (NF)-κB activity and IL-1β expression, maturation, and secretion. Various scropoliosides were extracted, isolated, and purified from Scrophularia dentata Royle ex Benth. We then [...] Read more.

We have previously shown that scropolioside B has higher anti-inflammatory activity than catalpol does after the inhibition of nuclear factor (NF)-κB activity and IL-1β expression, maturation, and secretion. Various scropoliosides were extracted, isolated, and purified from Scrophularia dentata Royle ex Benth. We then compared their anti-inflammatory activities against LPS-induced NF-κB activity, cytokines mRNA expression, IL-1β secretion, and cyclooxygenase-2 activity. The inhibitory effects of the scropoliosides varied depending on whether the 6-O-substituted cinnamyl moiety was linked to C′′ 2-OH, C′′3-OH, or C′′4-OH, and on the number of moieties linked, which is closely related to the enhancement of antiinflammatory activity. Among these compounds, scropolioside B had the strongest antiinflammatory effects. Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 741 KiB

Open AccessArticle

A Click Chemistry Approach towards Flavin-Cyclodextrin Conjugates—Bioinspired Sulfoxidation Catalysts

by Petra Tomanová¹, Jiří Šturala¹, Miloš Buděšínský² and Radek Cibulka^1,*

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

² Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nám. 2, 166 10 Prague 6, Czech Republic

Molecules 2015, 20(11), 19837-19848; https://doi.org/10.3390/molecules201119667 - 4 Nov 2015

Cited by 9 | Viewed by 7977

Abstract

A click chemistry approach based on the reaction between alkynylflavins and mono(6-azido-6-deoxy)-β-cyclodextrin has proven to be a useful tool for the synthesis of flavin-cyclodextrin conjugates studied as monooxygenase mimics in enantioselective sulfoxidations. Full article

(This article belongs to the Special Issue Design and Synthesis of Novel Conjugated and Non Conjugated Small Molecules)

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16 pages, 1806 KiB

Open AccessArticle

Anti-Lymphoma Efficacy Comparison of Anti-Cd20 Monoclonal Antibody-Targeted and Non-Targeted Star-Shaped Polymer-Prodrug Conjugates

by Ondřej Lidický¹, Olga Janoušková¹, Jiří Strohalm¹, Mahmudul Alam², Pavel Klener^2,3 and Tomáš Etrych^1,*

¹ Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovský Sq. 2, 162 06 Prague 6, Czech Republic

² Institute of Pathological Physiology, First Faculty of Medicine, Charles University in Prague, U Nemocnice 5, 128 53 Prague 2, Czech Republic

³ Department of Hematology, Charles University General Hospital in Prague, U Nemocnice 2, 128 08 Prague 2, Czech Republic

Molecules 2015, 20(11), 19849-19864; https://doi.org/10.3390/molecules201119664 - 4 Nov 2015

Cited by 19 | Viewed by 8591

Abstract

Here we describe the synthesis and biological properties of two types of star-shaped polymer-doxorubicin conjugates: non-targeted conjugate prepared as long-circulating high-molecular-weight (HMW) polymer prodrugs with a dendrimer core and a targeted conjugate with the anti-CD20 monoclonal antibody (mAb) rituximab (RTX). The copolymers were [...] Read more.

Here we describe the synthesis and biological properties of two types of star-shaped polymer-doxorubicin conjugates: non-targeted conjugate prepared as long-circulating high-molecular-weight (HMW) polymer prodrugs with a dendrimer core and a targeted conjugate with the anti-CD20 monoclonal antibody (mAb) rituximab (RTX). The copolymers were linked to the dendrimer core or to the reduced mAb via one-point attachment forming a star-shaped structure with a central antibody or dendrimer surrounded by hydrophilic polymer chains. The anticancer drug doxorubicin (DOX) was attached to the N-(2-hydroxypropyl)methacrylamide (HPMA)-based copolymer chain in star polymer systems via a pH-labile hydrazone linkage. Such polymer-DOX conjugates were fairly stable in aqueous solutions at pH 7.4, and the drug was readily released in mildly acidic environments at pH 5–5.5 by hydrolysis of the hydrazone bonds. The cytotoxicity of the polymer conjugates was tested on several CD20-positive or negative human cell lines. Similar levels of in vitro cytotoxicity were observed for all tested polymer conjugates regardless of type or structure. In vivo experiments using primary cell-based murine xenograft models of human diffuse large B-cell lymphoma confirmed the superior anti-lymphoma efficacy of the polymer-bound DOX conjugate when compared with the original drug. Targeting with RTX did not further enhance the anti-lymphoma efficacy relative to the non-targeted star polymer conjugate. Two mechanisms could play roles in these findings: changes in the binding ability to the CD-20 receptor and a significant loss of the immunological properties of RTX in the polymer conjugates. Full article

(This article belongs to the Collection Nanomedicine)

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13 pages, 356 KiB

Open AccessArticle

Polyphenolic Compositions and Chromatic Characteristics of Bog Bilberry Syrup Wines

by Shu-Xun Liu^1,†, Hang-Yu Yang^1,†, Si-Yu Li², Jia-Yue Zhang¹, Teng Li¹, Bao-Qing Zhu^1,* and Bo-Lin Zhang^1,*

¹ Beijing Key Laboratory of Forestry Food Processing and Safety, Department of Food science, College of Biological Sciences and Biotechnology, Beijing Forestry University, Beijing 10083, China

² Center for Viticulture and Enology, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing 100083, China

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 19865-19877; https://doi.org/10.3390/molecules201119662 - 4 Nov 2015

Cited by 30 | Viewed by 7671

Abstract

Phenolic compounds determine the color quality of fruit wines. In this study, the phenolic compound content and composition, color characteristics and changes during 6 months of bottle aging were studied in wines fermented with bog bilberry syrup under three different pHs. The total [...] Read more.

Phenolic compounds determine the color quality of fruit wines. In this study, the phenolic compound content and composition, color characteristics and changes during 6 months of bottle aging were studied in wines fermented with bog bilberry syrup under three different pHs. The total anthocyanins and total phenols were around 15.12–16.23 mg/L and 475.82 to 486.50 mg GAE/L in fresh wines and declined 22%–31% and about 11% in bottle aged wines, respectively. In fresh wines, eight anthocyanins, six phenolic aids and 14 flavonols, but no flavon-3-ols were identified; Malvidin-3-O-glucoside, petunidin-3-O-glucoside and delphinium-3-O-glucoside were the predominant pigments; Chlorogentic acid was the most abundant phenolic acid, and quercetin-3-O-galactoside and myricetin-3-O-galactoside accounted for nearly 90% of the total flavonols. During 6 months of bottle storage, the amounts of all the monomeric anthocyanins and phenolic acids were reduced dramatically, while the glycosidyl flavonols remained constant or were less reduced and their corresponding aglycones increased a lot. The effects of aging on blueberry wine color were described as the loss of color intensity with a dramatic change in color hue, from initial red-purple up to final red-brick nuances, while the pH of the fermentation matrix was negatively related to the color stability of aged wine. Full article

(This article belongs to the Section Natural Products Chemistry)

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8 pages, 539 KiB

Open AccessArticle

Long-Term Lithium Treatment Increases cPLA₂ and iPLA₂ Activity in Cultured Cortical and Hippocampal Neurons

by Vanessa De Jesus De-Paula, Daniel Shikanai Kerr, Marília Palma Fabiano De Carvalho, Evelin Lisete Schaeffer, Leda Leme Talib, Wagner Farid Gattaz and Orestes Vicente Forlenza^*

Laboratory of Neuroscience (LIM 27), Department and Institute of Psychiatry, Faculty of Medicine, University of Sao Paulo, São Paulo 05403-010, Brazil

Molecules 2015, 20(11), 19878-19885; https://doi.org/10.3390/molecules201119663 - 4 Nov 2015

Cited by 11 | Viewed by 7505

Abstract

Background: Experimental evidence supports the neuroprotective properties of lithium, with implications for the treatment and prevention of dementia and other neurodegenerative disorders. Lithium modulates critical intracellular pathways related to neurotrophic support, inflammatory response, autophagy and apoptosis. There is additional evidence indicating that lithium [...] Read more.

Background: Experimental evidence supports the neuroprotective properties of lithium, with implications for the treatment and prevention of dementia and other neurodegenerative disorders. Lithium modulates critical intracellular pathways related to neurotrophic support, inflammatory response, autophagy and apoptosis. There is additional evidence indicating that lithium may also affect membrane homeostasis. Objective: To investigate the effect of lithium on cytosolic phospholipase A₂ (PLA₂) activity, a key player on membrane phospholipid turnover which has been found to be reduced in blood and brain tissue of patients with Alzheimer’s disease (AD). Methods: Primary cultures of cortical and hippocampal neurons were treated for 7 days with different concentrations of lithium chloride (0.02 mM, 0.2 mM and 2 mM). A radio-enzymatic assay was used to determine the total activity of PLA₂ and two PLA₂ subtypes: cytosolic calcium-dependent (cPLA₂); and calcium-independent (iPLA₂). Results: cPLA₂ activity increased by 82% (0.02 mM; p = 0.05) and 26% (0.2 mM; p = 0.04) in cortical neurons and by 61% (0.2 mM; p = 0.03) and 57% (2 mM; p = 0.04) in hippocampal neurons. iPLA₂ activity was increased by 7% (0.2 mM; p = 0.04) and 13% (2 mM; p = 0.05) in cortical neurons and by 141% (0.02 mM; p = 0.0198) in hippocampal neurons. Conclusion: long-term lithium treatment increases membrane phospholipid metabolism in neurons through the activation of total, c- and iPLA₂. This effect is more prominent at sub-therapeutic concentrations of lithium, and the activation of distinct cytosolic PLA₂ subtypes is tissue specific, i.e., iPLA₂ in hippocampal neurons, and cPLA₂ in cortical neurons. Because PLA₂ activities are reported to be reduced in Alzheimer’s disease (AD) and bipolar disorder (BD), the present findings provide a possible mechanism by which long-term lithium treatment may be useful in the prevention of the disease. Full article

(This article belongs to the Special Issue Molecules against Alzheimer)

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14 pages, 3533 KiB

Open AccessArticle

Photostabilizing Efficiency of PVC in the Presence of Schiff Bases as Photostabilizers

by Emad Yousif¹

, Ahmed A. Al-Amiery^2,3,*

, Abdulhadi Kadihum⁴, Abdul Amir H. Kadhum³ and Abu Bakar Mohamad^3,5

¹ Department of Chemistry, College of Science, Al-Nahrain University, Baghdad 10072, Iraq

² Environmental Research Center, University of Technology (UOT), Baghdad 10001, Iraq

³ Department of Chemical & Process Engineering, University Kebangsaan Malaysia (UKM), Bangi, Selangor 43000, Malaysia

⁴ Department of Laser and Optoelectronics, University of Technology (UOT), Baghdad 10001, Iraq

⁵ Fuel Cell Institute, University Kebangsaan Malaysia (UKM), Bangi, Selangor 43000, Malaysia

Molecules 2015, 20(11), 19886-19899; https://doi.org/10.3390/molecules201119665 - 4 Nov 2015

Cited by 29 | Viewed by 7614

Abstract

The photostabilization of polyvinyl chloride (PVC) films by Schiff bases was investigated. Polyvinyl chloride films containing 0.5 wt % Schiff bases were produced using the same casting method as that used for additive-free PVC films from tetrahydrofuran (THF) solvent. The photostabilization activities of [...] Read more.

The photostabilization of polyvinyl chloride (PVC) films by Schiff bases was investigated. Polyvinyl chloride films containing 0.5 wt % Schiff bases were produced using the same casting method as that used for additive-free PVC films from tetrahydrofuran (THF) solvent. The photostabilization activities of these compounds were determined by monitoring the carbonyl, polyene and hydroxyl indices with irradiation time. The changes in viscosity average molecular weight of PVC with irradiation time were also monitored using THF as a solvent. The quantum yield of chain scission (Φ_cs) for the studied complexes in PVC was estimated to range between 4.72 and 8.99 × 10⁻⁸. According to the experimental results, several mechanisms were suggested, depending on the structure of the additive. Ultra violet (UV) absorption, peroxide decomposition and radical scavenging were suggested as the photostabilizing mechanisms. Full article

(This article belongs to the Section Photochemistry)

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7 pages, 1941 KiB

Open AccessArticle

Hazardous Doping for Photo-Electrochemical Conversion: The Case of Nb-Doped Fe₂O₃ from First Principles

by Natav Yatom and Maytal Caspary Toroker^*

Department of Materials Science and Engineering, Technion—Israel Institute of Technology, Haifa 32000, Israel

Molecules 2015, 20(11), 19900-19906; https://doi.org/10.3390/molecules201119668 - 4 Nov 2015

Cited by 28 | Viewed by 7066

Abstract

The challenge of improving the efficiency of photo-electrochemical devices is often addressed through doping. However, this strategy could harm performance. Specifically, as demonstrated in a recent experiment, doping one of the most widely used materials for water splitting, iron (III) oxide (Fe₂ [...] Read more.

The challenge of improving the efficiency of photo-electrochemical devices is often addressed through doping. However, this strategy could harm performance. Specifically, as demonstrated in a recent experiment, doping one of the most widely used materials for water splitting, iron (III) oxide (Fe₂O₃), with niobium (Nb) can still result in limited efficiency. In order to better understand the hazardous effect of doping, we use Density Functional Theory (DFT)+U for the case of Nb-doped Fe₂O₃. We find a direct correlation between the charge of the dopant, the charge on surface of the Fe₂O₃ material, and the overpotential required for water oxidation reaction. We believe that this work contributes to advancing our understanding of how to select effective dopants for materials. Full article

(This article belongs to the Special Issue Molecular Engineering for Electrochemical Power Sources)

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7 pages, 1000 KiB

Open AccessCommunication

Radical Scavenging by Acetone: A New Perspective to Understand Laccase/ABTS Inactivation and to Recover Redox Mediator

by Hao Liu^1,*,†, Pandeng Zhou^2,†, Xing Wu¹, Jianliang Sun¹ and Shicheng Chen^3,*

¹ State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Guangzhou 510640, China

² School of Chemistry and Environmental Engineering, Hunan City University, Yiyang 413000, China

³ Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 19907-19913; https://doi.org/10.3390/molecules201119672 - 4 Nov 2015

Cited by 18 | Viewed by 9411

Abstract

The biosynthetic utilization of laccase/mediator system is problematic because the use of organic cosolvent causes significant inhibition of laccase activity. This work explored how the organic cosolvent impacts on the laccase catalytic capacity towards 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) in aqueous solution. Effects of acetone [...] Read more.

The biosynthetic utilization of laccase/mediator system is problematic because the use of organic cosolvent causes significant inhibition of laccase activity. This work explored how the organic cosolvent impacts on the laccase catalytic capacity towards 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) in aqueous solution. Effects of acetone on the kinetic constants of laccase were determined and the results showed K_m and V_max varied exponentially with increasing acetone content. Acetone as well as some other cosolvents could transform ABTS radicals into its reductive form. The content of acetone in media significantly affected the radical scavenging rates. Up to 95% of the oxidized ABTS was successfully recovered in 80% (v/v) acetone in 60 min. This allows ABTS recycles at least six times with 70%–75% of active radicals recovered after each cycle. This solvent-based recovery strategy may help improve the economic feasibility of laccase/ABTS system in biosynthesis. Full article

(This article belongs to the Section Bioorganic Chemistry)

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15 pages, 3817 KiB

Open AccessArticle

Synthesis, Density Functional Theory (DFT), Urease Inhibition and Antimicrobial Activities of 5-Aryl Thiophenes Bearing Sulphonylacetamide Moieties

by Mnaza Noreen¹, Nasir Rasool^1,*, Yasmeen Gull¹, Muhammad Zubair¹, Tariq Mahmood², Khurshid Ayub², Faiz-ul-Hassan Nasim³, Asma Yaqoob³, Muhammad Zia-Ul-Haq⁴ and Vincenzo De Feo^5,*

¹ Department of Chemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan

² Department of Chemistry, COMSATS Institute of Information Technology, University Road, Tobe Camp, Abbottabad 22060, Pakistan

³ Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63000, Pakistan

⁴ The Patent Office, Karachi 74200, Pakistan

⁵ Department of Pharmaceutical and Biomedical Sciences, University of Salerno, Via Ponte don Melillo, Fisciano (Salerno) I-84084, Italy

Molecules 2015, 20(11), 19914-19928; https://doi.org/10.3390/molecules201119661 - 5 Nov 2015

Cited by 41 | Viewed by 7675

Abstract

A variety of novel 5-aryl thiophenes 4a–g containing sulphonylacetamide (sulfacetamide) groups were synthesized in appreciable yields via Pd[0] Suzuki cross coupling reactions. The structures of these newly synthesized compounds were determined using spectral data and elemental analysis. Density functional theory (DFT) [...] Read more.

A variety of novel 5-aryl thiophenes 4a–g containing sulphonylacetamide (sulfacetamide) groups were synthesized in appreciable yields via Pd[0] Suzuki cross coupling reactions. The structures of these newly synthesized compounds were determined using spectral data and elemental analysis. Density functional theory (DFT) studies were performed using the B3LYP/6-31G (d, p) basis set to gain insight into their structural properties. Frontier molecular orbital (FMOs) analysis of all compounds 4a–g was computed at the same level of theory to get an idea about their kinetic stability. The molecular electrostatic potential (MEP) mapping over the entire stabilized geometries of the molecules indicated the reactive sites. First hyperpolarizability analysis (nonlinear optical response) were simulated at the B3LYP/6-31G (d, p) level of theory as well. The compounds were further evaluated for their promising antibacterial and anti-urease activities. In this case, the antibacterial activities were estimated by the agar well diffusion method, whereas the anti-urease activities of these compounds were determined using the indophenol method by quantifying the evolved ammonia produced. The results revealed that all the sulfacetamide derivatives displayed antibacterial activity against Bacillus subtiles, Escherichia coli, Staphylococcus aureus, Shigella dysenteriae, Salmonella typhae, Pseudomonas aeruginosa at various concentrations. Furthermore, the compound 4g N-((5-(4-chlorophenyl)thiophen-2-yl)sulfonyl) acetamide showed excellent urease inhibition with percentage inhibition activity ~46.23 ± 0.11 at 15 µg/mL with IC₅₀ 17.1 µg/mL. Moreover, some other compounds 4a–f also exhibited very good inhibition against urease enzyme. Full article

(This article belongs to the Section Medicinal Chemistry)

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7 pages, 191 KiB

Open AccessArticle

Development and Characterization of Polymorphic Microsatellite Markers for Sedum sarmentosum (Crassulaceae) and Their Cross-Species Transferability

by Jing Xu^*, Fu-Yuan Hou, Ding-Rong Wan, Sha Wang, Dong-Mei Xu and Guang-Zhong Yang

College of Pharmacy, South Central University for Nationalities, 708 Minyuan Road, Wuhan 430074, China

Molecules 2015, 20(11), 19929-19935; https://doi.org/10.3390/molecules201119669 - 5 Nov 2015

Cited by 3 | Viewed by 5315

Abstract

Sedum sarmentosum is an important Chinese medicinal herb that exhibits anti-inflammatory, anti-angiogenic and anti-nociceptive properties. However, little is known about its genetic background. The first set of 14 microsatellite markers were isolated and characterized for S. sarmentosum using an SSR-enriched library. Fourteen polymorphic [...] Read more.

Sedum sarmentosum is an important Chinese medicinal herb that exhibits anti-inflammatory, anti-angiogenic and anti-nociceptive properties. However, little is known about its genetic background. The first set of 14 microsatellite markers were isolated and characterized for S. sarmentosum using an SSR-enriched library. Fourteen polymorphic microsatellite markers were acquired with satisfactory amplifications and a polymorphic pattern in 48 S. sarmentosum individuals. The number of alleles ranged from 3 to 15. The observed and expected heterozygosities varied from 0.0833 to 0.8750 and 0.2168 to 0.9063, respectively. Two loci showed significant departure from the Hardy-Weinberg equilibrium. Cross-species amplification was carried out in other Sedum species. High rates of cross-species amplification were observed. The transferability value ranged from 85.7% in S. lineare to 64.3% in S. ellacombianum. These markers will be valuable for studying the genetic variation, population structure and germplasm characterization of S. sarmentosum and related Sedum species. Full article

(This article belongs to the Section Molecular Diversity)

11 pages, 942 KiB

Open AccessArticle

Production of Nanoemulsions from Palm-Based Tocotrienol Rich Fraction by Microfluidization

by Pik Seah Goh¹, Mei Han Ng^2,*, Yuen May Choo², Nasrulhaq Boyce Amru¹ and Cheng Hock Chuah^3,*

¹ Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia

² Milling & Processing Unit, Engineering & Processing Division, Malaysian Palm Oil Board, 6 Persiaran Institusi, Bandar Baru Bangi, 43000 Kajang, Malaysia

³ Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia

Molecules 2015, 20(11), 19936-19946; https://doi.org/10.3390/molecules201119666 - 5 Nov 2015

Cited by 45 | Viewed by 7894

Abstract

In the present study, tocotrienol rich fraction (TRF) nanoemulsions were produced as an alternative approach to improve solubility and absorption of tocotrienols. In the present study, droplet size obtained after 10 cycles of homogenization with increasing pressure was found to decrease from 120 [...] Read more.

In the present study, tocotrienol rich fraction (TRF) nanoemulsions were produced as an alternative approach to improve solubility and absorption of tocotrienols. In the present study, droplet size obtained after 10 cycles of homogenization with increasing pressure was found to decrease from 120 to 65.1 nm. Nanoemulsions stabilized with Tween series alone or emulsifier blend Brij 35:Span 80 (0.6:0.4 w/w) homogenized at 25,000 psi and 10 cycles, produced droplet size less than 100 nm and a narrow size distribution with a polydispersity index (PDI) value lower than 0.2. However blend of Tween series with Span 80 produced nanoemulsions with droplet size larger than 200 nm. This work has also demonstrated the amount of tocols losses in TRF nanoemulsion stabilized Tweens alone or emulsifier blend Brij 35:Span 80 (0.6:0.4 w/w) ranged between 3%–25%. This can be attributed to the interfacial film formed surrounding the droplets exhibited different level of oxidative stability against heat and free radicals created during high pressure emulsification. Full article

(This article belongs to the Special Issue Pharmaceutical Nanotechnology: Novel Approaches)

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11 pages, 561 KiB

Open AccessArticle

Phenolic Compounds from the Flowers of Bombax malabaricum and Their Antioxidant and Antiviral Activities

by Yu-Bo Zhang^1,2,†, Peng Wu^1,3,†, Xiao-Li Zhang^1,2, Chao Xia^1,2, Guo-Qiang Li¹, Wen-Cai Ye¹, Guo-Cai Wang^1,2,* and Yao-Lan Li^1,2,*

¹ Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China

² Shenzhen Engineering Laboratory of Lingnan Herbal Resource Development and Application, Shenzhen Institute for Drug Control, Shenzhen 518057, China

³ International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 19947-19957; https://doi.org/10.3390/molecules201119660 - 5 Nov 2015

Cited by 30 | Viewed by 8274

Abstract

Three new phenolic compounds 1–3 and twenty known ones 4–23 were isolated from the flowers of Bombax malabaricum. Their chemical structures were elucidated by spectroscopic analyses (IR, ESI-MS, HR-ESI-MS, 1D- and 2D-NMR) and chemical reactions. The antioxidant capacities of [...] Read more.

Three new phenolic compounds 1–3 and twenty known ones 4–23 were isolated from the flowers of Bombax malabaricum. Their chemical structures were elucidated by spectroscopic analyses (IR, ESI-MS, HR-ESI-MS, 1D- and 2D-NMR) and chemical reactions. The antioxidant capacities of the isolated compounds were tested using FRAP and DPPH radical-scavenging assays, and compounds 4, 6, 8, 12, as well as the new compound 2, exhibited stronger antioxidant activities than ascorbic acid. Furthermore, all of compounds were tested for their antiviral activities against RSV by the CPE reduction assay and plaque reduction assay. Compounds 4, 10, 12 possess in vitro antiviral activities, and compound 10 exhibits potent anti-RSV effects, comparable to the positive control ribavirin. Full article

(This article belongs to the Special Issue Recent Advances in Plant Phenolics)

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13 pages, 2273 KiB

Open AccessArticle

Water-Soluble Lignins from Different Bioenergy Crops Stimulate the Early Development of Maize (Zea mays, L.)

by Davide Savy^*, Vincenza Cozzolino, Giovanni Vinci, Antonio Nebbioso and Alessandro Piccolo^*

Interdepartmental Research Center of Nuclear Magnetic Resonance for the Environment, Food Processing and New Materials (CERMANU), Via Università 100, Portici 80055, Italy

Molecules 2015, 20(11), 19958-19970; https://doi.org/10.3390/molecules201119671 - 5 Nov 2015

Cited by 47 | Viewed by 7618

Abstract

The molecular composition of water-soluble lignins isolated from four non-food bioenergy crops (cardoon CAR, eucalyptus EUC, and two black poplars RIP and LIM) was characterized in detail, and their potential bioactivity towards maize germination and early growth evaluated. Lignins were found to not [...] Read more.

The molecular composition of water-soluble lignins isolated from four non-food bioenergy crops (cardoon CAR, eucalyptus EUC, and two black poplars RIP and LIM) was characterized in detail, and their potential bioactivity towards maize germination and early growth evaluated. Lignins were found to not affect seed germination rates, but stimulated the maize seedling development, though to a different extent. RIP promoted root elongation, while CAR only stimulated the length of lateral seminal roots and coleoptile, and LIM improved only the coleoptile development. The most significant bioactivity of CAR was related to its large content of aliphatic OH groups, C-O carbons and lowest hydrophobicity, as assessed by ³¹P-NMR and ¹³C-CPMAS-NMR spectroscopies. Less bioactive RIP and LIM lignins were similar in composition, but their stimulation of maize seedling was different. This was accounted to their diverse content of aliphatic OH groups and S- and G-type molecules. The poorest bioactivity of the EUC lignin was attributed to its smallest content of aliphatic OH groups and largest hydrophobicity. Both these features may be conducive of a EUC conformational structure tight enough to prevent its alteration by organic acids exuded from vegetal tissues. Conversely the more labile conformational arrangements of the other more hydrophilic lignin extracts promoted their bioactivity by releasing biologically active molecules upon the action of exuded organic acids. Our findings indicate that water-soluble lignins from non-food crops may be effectively used as plant biostimulants, thus contributing to increase the economic and ecological liability of bio-based industries. Full article

(This article belongs to the Special Issue Biocatalytic Lignin Modification)

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13 pages, 2388 KiB

Open AccessArticle

Immobilization of Cyclooxygenase-2 on Silica Gel Microspheres: Optimization and Characterization

by Qian Shi^1,2, Junhui Chen^2,*, Yanlong Wang², Zhaoyong Li², Xianguo Li^1,*, Chengjun Sun² and Li Zheng²

¹ College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao 266100, China

² Research Center for Marine Ecology, The First Institute of Oceanography, State Oceanic Administration, Qingdao 266061, China

Molecules 2015, 20(11), 19971-19983; https://doi.org/10.3390/molecules201119670 - 5 Nov 2015

Cited by 12 | Viewed by 6594

Abstract

In this study, immobilized COX-2 was successfully constructed through glutaraldehyde-mediated covalent coupling on functional silica gel microspheres. The optimum conditions, properties, and morphological characteristics of the immobilized COX-2 were investigated. The optimal immobilization process was as follows: about 0.02 g of aminated silica [...] Read more.

In this study, immobilized COX-2 was successfully constructed through glutaraldehyde-mediated covalent coupling on functional silica gel microspheres. The optimum conditions, properties, and morphological characteristics of the immobilized COX-2 were investigated. The optimal immobilization process was as follows: about 0.02 g of aminated silica gel microspheres was activated by 0.25% GA solution for 6 h and mixed with 5 U of free recombinant COX-2 solution. Then, the mixture was shaken for 8 h at 20 °C. Results showed that the immobilized COX-2 produced by this method exhibited excellent biocatalytic activity, equivalent to that of free COX-2 under the test conditions employed. The best biocatalytic activity of immobilized COX-2 appeared at pH 8.0 and still maintained at about 84% (RSD < 7.39%, n = 3) at pH 10.0. For temperature tolerance, immobilized COX-2 exhibited its maximum biocatalytic activity at 40 °C and about 68% (RSD < 6.99%, n = 3) of the activity was maintained at 60 °C. The immobilized COX-2 retained over 85% (RSD < 7.26%, n = 3) of its initial biocatalytic activity after five cycles, and after 10 days storage, the catalytic activity of immobilized COX-2 still maintained at about 95% (RSD < 3.08%, n = 3). These characteristics ensured the convenient use of the immobilized COX-2 and reduced its production cost. Full article

(This article belongs to the Section Molecular Diversity)

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30 pages, 3027 KiB

Open AccessArticle

Efficient Syntheses of 1,2,3-Triazoloamide Derivatives Using Solid- and Solution-Phase Synthetic Approaches

by Doohyun Lee¹, Daehun Kim¹, Seungyeon Lee¹, Taegeum Kim¹, Joobin Kim¹, Sohee Kim¹, Kwang-Hyeon Liu¹, Sangkyu Lee¹, Jong-Sup Bae¹, Kyung-Sik Song¹, Chang-Woo Cho², Youn Kyung Son³, Dong Jae Baek^4,* and Taeho Lee^1,*

¹ College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 702-701, Korea

² Department of Chemistry, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 702-701, Korea

³ National Institute of Biological Resources, Hwangyeong-ro 42, Seo-gu, Incheon 404-708, Korea

⁴ College of Pharmacy, Natural Medicine Research Institute, Mokpo National University, 1666 Youngsan-ro, Muan-gun, Jeonnam 534-729, Korea

Molecules 2015, 20(11), 19984-20013; https://doi.org/10.3390/molecules201119673 - 5 Nov 2015

Cited by 9 | Viewed by 8471

Abstract

Efficient synthetic routes for the preparation of secondary and tertiary 1,2,3-triazoloamide derivatives were developed. A secondary α-1,2,3-triazoloamide library was constructed and expanded by a previously developed solid-phase synthetic route and a tertiary 1,2,3-triazoloamide library was constructed by a parallel solution-phase synthetic route. The [...] Read more.

Efficient synthetic routes for the preparation of secondary and tertiary 1,2,3-triazoloamide derivatives were developed. A secondary α-1,2,3-triazoloamide library was constructed and expanded by a previously developed solid-phase synthetic route and a tertiary 1,2,3-triazoloamide library was constructed by a parallel solution-phase synthetic route. The synthetic routes rely on amide formation with secondary amines and chloro-acid chlorides; S_N2 reaction with sodium azide; and the selective [3 + 2] Hüisgen cycloaddition with appropriate terminal alkynes. The target secondary and tertiary 1,2,3-triazoloamide derivatives were obtained with three-diversity points in excellent overall yields and purities using the reported solid- and solution-phase synthetic routes, respectively. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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17 pages, 1025 KiB

Open AccessArticle

Bitter Gentian Teas: Nutritional and Phytochemical Profiles, Polysaccharide Characterisation and Bioactivity

by Daniil N. Olennikov^1,*

, Nina I. Kashchenko¹, Nadezhda K. Chirikova², Lena P. Koryakina³ and Leonid N. Vladimirov³

¹ Institute of General and Experimental Biology, Siberian Division, Russian Academy of Science, Sakh’yanovoy Str., 6, Ulan-Ude 670047, Russia

² Department of Biochemistry and Biotechnology, North-Eastern Federal University, 58 Belinsky Str., Yakutsk 677027, Russia

³ Faculty of the Veterinarian Medicine, Yakut State Agricultural Academy, 15 Krasil’nikova Str., Yakutsk 677007, Russia

Molecules 2015, 20(11), 20014-20030; https://doi.org/10.3390/molecules201119674 - 5 Nov 2015

Cited by 44 | Viewed by 8653

Abstract

As a result of the wide distribution of herbal teas the data on nutritional characterisation, chemical profile and biological activity of these products are required. The decoctions of Gentiana algida, G. decumbens, G. macrophylla and G. triflora herb teas were nutritionally [...] Read more.

As a result of the wide distribution of herbal teas the data on nutritional characterisation, chemical profile and biological activity of these products are required. The decoctions of Gentiana algida, G. decumbens, G. macrophylla and G. triflora herb teas were nutritionally characterized with respect to their macronutrients, demonstrating the predominance of polysaccharides and low lipid content. Gentian decoctions were also submitted to a microcolumn RP-HPLC-UV analysis of phytochemicals demonstrating a high content of iridoids (177.18–641.04 μg/mL) and flavonoids (89.15–405.71 μg/mL). Additionally, mangiferin was detected in samples of G. triflora tea (19.89 μg/mL). Five free sugars (fructose, glucose, sucrose, gentiobiose, gentianose) were identified in all gentian teas studied, as well as six organic acids (malic, citric, tartaric, oxalic, succinic, quinic). Pectic polysaccharides with a high content of rhamnogalacturonans and arabinogalactans were also identified and characterized in gentian decoctions for the first time. Gentian tea decoctions and their specific compounds (gentiopicroside, loganic acid-6′-O-β-d-glucoside, isoorientin, isoorientin-4′-O-β-d-glucoside, mangiferin, water-soluble polysaccharides) showed a promising antimicrobial, anti-inflammatory and antioxidant potentials. Evidences obtained indicate the prospective use of gentian herb teas as food products and medicines. Full article

(This article belongs to the Collection Herbal Medicine Research)

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11 pages, 1384 KiB

Open AccessArticle

Pharmacokinetics of Ginkgolide B after Oral Administration of Three Different Ginkgolide B Formulations in Beagle Dogs

by Jie Zhao^1,†, Ting Geng^1,†, Qi Wang², Haihong Si¹, Xiaoping Sun¹, Qingming Guo¹, Yanjing Li¹, Wenzhe Huang¹, Gang Ding¹ and Wei Xiao^1,*

¹ State Key Lab of New-Tech for Chinese Medicine Pharmaceutical Process, Kanion Pharmaceutical Co. Ltd, Lianyungang 222000, Jiangsu, China

² Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 20031-20041; https://doi.org/10.3390/molecules201119678 - 6 Nov 2015

Cited by 12 | Viewed by 7009 | Correction

Abstract

Ginkgolide B (GB), an important active constituent of Ginkgo biloba extract, has been used in clinical applications for the treatment of dementia, cerebral insufficiency or related cognitive decline. To investigate the main pharmacokinetic characteristics of three different GB formulations in beagle dogs, a [...] Read more.

Ginkgolide B (GB), an important active constituent of Ginkgo biloba extract, has been used in clinical applications for the treatment of dementia, cerebral insufficiency or related cognitive decline. To investigate the main pharmacokinetic characteristics of three different GB formulations in beagle dogs, a simple, specific and sensitive LC-MS/MS method was established and validated. The separation of the analytes was achieved on an Agilent Eclipse Plus C₁₈ column (1.8 μm, 2.1 × 50 mm) with a mobile phase consisting of water and acetonitrile. The flow rate was set at 0.4 mL/min. Quantitation was performed using multiple reaction monitoring (MRM) in negative ion mode, with the transitions at m/z (Q1/Q3) 423.1/367.1 for GB and m/z 269.3/170.0 for IS. The linear calibration curve of GB was obtained over the concentration range of 2–200 ng/mL. The intra- and inter-day precisions were <15% and the accuracies were within ±12.7%. The validated method was applied to compare the pharmacokinetic characteristics of GB in healthy beagle dogs after oral administration of three formulations (HME08, GB capsule prepared by hot-melt extrusion technology; LL06, GB pellet prepared by liquid layer technology; conventional GB tablet). The C_max values of GB from different formulations in beagle dog plasma were 309.2, 192.4 and 66.6 µg/L, and the AUC values were 606.7, 419.1 and 236.2 µg/L·h, respectively. The data suggested that the exposure level of GB from HME08 and LL06 in beagle dog plasma was greatly improved compared with conventional tablets. This study should be helpful for the design and development of oral GB preparations. Full article

(This article belongs to the Section Medicinal Chemistry)

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21 pages, 4134 KiB

Open AccessReview

Synthesis and Chemistry of Organic Geminal Di- and Triazides

by Andreas P. Häring and Stefan F. Kirsch^*

Organic Chemistry, Bergische Universität Wuppertal, Gaußstraße 20, 42119 Wuppertal, Germany

Molecules 2015, 20(11), 20042-20062; https://doi.org/10.3390/molecules201119675 - 6 Nov 2015

Cited by 39 | Viewed by 11065

Abstract

This review recapitulates all available literature dealing with the synthesis and reactivity of geminal organic di- and triazides. These compound classes are, to a large extent, unexplored despite their promising chemical properties and their simple preparation. In addition, the chemistry of carbonyl diazide [...] Read more.

This review recapitulates all available literature dealing with the synthesis and reactivity of geminal organic di- and triazides. These compound classes are, to a large extent, unexplored despite their promising chemical properties and their simple preparation. In addition, the chemistry of carbonyl diazide (2) and tetraazidomethane (105) is described in separate sections. Full article

(This article belongs to the Special Issue Organic Azides)

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16 pages, 1352 KiB

Open AccessArticle

Design, Synthesis and in Vivo Evaluation of Novel Glycosylated Sulfonylureas as Antihyperglycemic Agents

by Ghadeer A. R. Y. Suaifan^1,*, Mayadah B. Shehadeh¹, Rula M. Darwish², Hebah Al-Ijel¹ and Vincenzo Abbate³

¹ Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman 11942, Jordan

² Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The University of Jordan, Amman 11942, Jordan

³ Institute of Pharmaceutical Science, King’s College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK

Molecules 2015, 20(11), 20063-20078; https://doi.org/10.3390/molecules201119676 - 6 Nov 2015

Cited by 13 | Viewed by 11060

Abstract

Sulphonylurea compounds have versatile activities such as antidiabetic, diuretic, herbicide, oncolytic, antimalarial, antifungal and anticancer. The present study describes the design, synthesis and in vivo testing of novel glycosylated aryl sulfonylurea compounds as antihyperglycaemic agents in streptozocine-induced diabetic mice. The rational for the [...] Read more.

Sulphonylurea compounds have versatile activities such as antidiabetic, diuretic, herbicide, oncolytic, antimalarial, antifungal and anticancer. The present study describes the design, synthesis and in vivo testing of novel glycosylated aryl sulfonylurea compounds as antihyperglycaemic agents in streptozocine-induced diabetic mice. The rational for the introduction of the glucosamine moiety is to enhance selective drug uptake by pancreatic β-cells in order to decrease the cardiotoxic side effect commonly associated with sulfonylurea agents. 2-Deoxy-2-(4-chlorophenylsulfonylurea)-d-glucopyranose was found to be the most potent antihyperglycaemic agents among the synthesized compounds in diabetic mice. This investigation indicates the importance of this novel class as potential antihyperglycaemic agents. Full article

(This article belongs to the Section Medicinal Chemistry)

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28 pages, 3152 KiB

Open AccessArticle

Synergy and Other Interactions between Polymethoxyflavones from Citrus Byproducts

by Benito F. García, Ascensión Torres and Francisco A. Macías^*

Allelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), Campus de Excelencia Internacional (ceiA3), Faculty of Science, University of Cadiz, C/República Saharaui n 7, 11510 Puerto Real, (Cádiz), Spain

Molecules 2015, 20(11), 20079-20106; https://doi.org/10.3390/molecules201119677 - 6 Nov 2015

Cited by 29 | Viewed by 12897

Abstract

The citrus by-products released from citrus processing plants may contain high levels of potentially bioactive compounds such as flavonoids, which are a widely distributed group of polyphenolic compounds with health-related properties based on their antioxidant activity. In the study reported here, the potential [...] Read more.

The citrus by-products released from citrus processing plants may contain high levels of potentially bioactive compounds such as flavonoids, which are a widely distributed group of polyphenolic compounds with health-related properties based on their antioxidant activity. In the study reported here, the potential bioactivities and antioxidant activities of extracts, fractions and compounds from citrus by-products were evaluated along with the chemical interactions of binary mixtures of compounds and complex mixtures. The bioactivities and interactions were evaluated in wheat coleoptile bioassays and the antioxidant activity was evaluated by the al DPPH (2,2-diphenyl-1-picrylhdrazyl radical) radical scavenging assay. The extracts, fractions and most of the isolated compounds (mainly polymethoxyflavones) showed high activity in the wheat coleoptile bioassay. However, the antioxidant activity was not consistently high, except in the acetone extract fractions. Moreover, a study of the interactions with binary mixtures of polymethoxyflavones showed the occurrence of synergistic effects. The complex mixtures of fractions composed mainly of polymethoxyflavones caused a synergistic effect when it was added to a bioactive compound such as anethole. The results reported here highlight a new application for the wheat coleoptile bioassay as a quick tool to detect potential synergistic effects in compounds or mixtures. Full article

(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)

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11 pages, 948 KiB

Open AccessArticle

Extremely Randomized Machine Learning Methods for Compound Activity Prediction

by Wojciech M. Czarnecki¹, Sabina Podlewska^2,3

and Andrzej J. Bojarski^2,*

¹ Faculty of Mathematics and Computer Science, Jagiellonian University, Lojasiewicza 6, 30-348 Krakow, Poland

² Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland

³ Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland

Molecules 2015, 20(11), 20107-20117; https://doi.org/10.3390/molecules201119679 - 9 Nov 2015

Cited by 9 | Viewed by 6579

Abstract

Speed, a relatively low requirement for computational resources and high effectiveness of the evaluation of the bioactivity of compounds have caused a rapid growth of interest in the application of machine learning methods to virtual screening tasks. However, due to the growth of [...] Read more.

Speed, a relatively low requirement for computational resources and high effectiveness of the evaluation of the bioactivity of compounds have caused a rapid growth of interest in the application of machine learning methods to virtual screening tasks. However, due to the growth of the amount of data also in cheminformatics and related fields, the aim of research has shifted not only towards the development of algorithms of high predictive power but also towards the simplification of previously existing methods to obtain results more quickly. In the study, we tested two approaches belonging to the group of so-called ‘extremely randomized methods’—Extreme Entropy Machine and Extremely Randomized Trees—for their ability to properly identify compounds that have activity towards particular protein targets. These methods were compared with their ‘non-extreme’ competitors, i.e., Support Vector Machine and Random Forest. The extreme approaches were not only found out to improve the efficiency of the classification of bioactive compounds, but they were also proved to be less computationally complex, requiring fewer steps to perform an optimization procedure. Full article

(This article belongs to the Special Issue Chemoinformatics)

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13 pages, 2153 KiB

Open AccessArticle

Design and Synthesis of New 2-Aryl-4,5-Dihydro-thiazole Analogues: In Vitro Antibacterial Activities and Preliminary Mechanism of Action

by Fangfang Tan^1,†, Baojun Shi^2,†, Jian Li¹, Wenjun Wu² and Jiwen Zhang^1,2,*

¹ College of Science, Northwest Agriculture and Forestry University, Yangling 712100, China

² Institute of Pesticide Science, Northwest Agriculture and Forestry University, Yangling 712100, China

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 20118-20130; https://doi.org/10.3390/molecules201119680 - 9 Nov 2015

Cited by 14 | Viewed by 7447

Abstract

Sixty 2-aryl-4,5-dihydrothiazoles were designed and synthesized in yields ranging from 64% to 89% from cysteine and substituted-benzonitriles via a novel metal- and catalyst-free method. The structures of the title compounds were confirmed mainly by NMR spectral data analysis. Antibacterial activity assays showed that [...] Read more.

Sixty 2-aryl-4,5-dihydrothiazoles were designed and synthesized in yields ranging from 64% to 89% from cysteine and substituted-benzonitriles via a novel metal- and catalyst-free method. The structures of the title compounds were confirmed mainly by NMR spectral data analysis. Antibacterial activity assays showed that the compounds (S)-2-(2′-hydroxyphenyl)-4-hydroxy-methyl- 4,5-dihydrothiazole (7h) and (R)-2-(2′-hydroxyphenyl)-4-hydroxymethyl-4,5-dihydro-thiazole (7h′) exhibited significant inhibition against Ralstonia solanacearum, Pseudomonas syringae pv. actinidiae, Bacillus subtilis and Bacillus cereus, with minimum inhibitory concentrations (MICs) ranging from 3.91 to 31.24 μg·mL⁻¹. The effect of substituents showed that not only electron-withdrawing groups, but also electron-donating groups could abolish the antibacterial activities unless a 2′-hydroxy group was introduced on the 2-aryl substituent of the 4,5-dihydrothiazole analogues. The results of scanning electron microscope (SEM) and fatty acid exposure experiments indicated that these antibacterial compounds influence fatty acid synthesis in the tested bacteria. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 3156 KiB

Open AccessArticle

Molecular Differentiated Initiator Reactivity in the Synthesis of Poly(caprolactone)-Based Hydrophobic Homopolymer and Amphiphilic Core Corona Star Polymers

by Eileen Deng¹, Nam T. Nguyen^1,2,†, Frédéric Hild^1,2, Ian E. Hamilton¹, Georgios Dimitrakis¹, Samuel W. Kingman¹, Phei-Li Lau³ and Derek J. Irvine^1,*

¹ Department of Chemical and Environmental Engineering, Faculty of Engineering, University of Nottingham, Nottingham NG7 2RD, UK

² School of Chemistry, University of Nottingham, Nottingham NG7 2RD, UK

³ Department of Chemical and Environmental Engineering, University of Nottingham Malaysia Campus, Jalan Broga, Semenyih 43500, Selangor Darul Ehsan, Malaysia

^† Current address: School of Biotechnology, International University, Vietnam National University, Ho Chi Minh City, Vietnam

Molecules 2015, 20(11), 20131-20145; https://doi.org/10.3390/molecules201119681 - 9 Nov 2015

Cited by 7 | Viewed by 8231

Abstract

Macromolecules that possess three-dimensional, branched molecular structures are of great interest because they exhibit significantly differentiated application performance compared to conventional linear (straight chain) polymers. This paper reports the synthesis of 3- and 4-arm star branched polymers via ring opening polymerisation (ROP) utilising [...] Read more.

Macromolecules that possess three-dimensional, branched molecular structures are of great interest because they exhibit significantly differentiated application performance compared to conventional linear (straight chain) polymers. This paper reports the synthesis of 3- and 4-arm star branched polymers via ring opening polymerisation (ROP) utilising multi-functional hydroxyl initiators and Sn(Oct)₂asprecatalyst. The structures produced include mono-functional hydrophobic and multi-functional amphiphilic core corona stars. The characteristics of the synthetic process were shown to be principally dependent upon the physical/dielectric properties of the initiators used. ROP’s using initiators that were more available to become directly involved with the Sn(Oct)₂ in the “in-situ” formation of the true catalytic species were observed to require shorter reaction times. Use of microwave heating (MWH) in homopolymer star synthesis reduced reaction times compared to conventional heating (CH) equivalents, this was attributed to an increased rate of “in-situ” catalyst formation. However, in amphiphilic core corona star formation, the MWH polymerisations exhibited slower propagation rates than CH equivalents. This was attributed to macro-structuring within the reaction medium, which reduced the potential for reaction. It was concluded that CH experiments were less affected by this macro-structuring because it was disrupted by the thermal currents/gradients caused by the conductive/convective heating mechanisms. These gradients are much reduced/absent with MWH because it selectively heats specific species simultaneously throughout the entire volume of the reaction medium. These partitioning problems were overcome by introducing additional quantities of the species that had been determined to selectively heat. Full article

(This article belongs to the Special Issue Microwave-Assisted Organic Synthesis)

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15 pages, 40226 KiB

Open AccessArticle

Membrane Disintegration Caused by the Steroid Saponin Digitonin Is Related to the Presence of Cholesterol

by Ikhwan Resmala Sudji¹, Yamunadevi Subburaj^2,3, Nataliya Frenkel^4,5, Ana J. García-Sáez² and Michael Wink^1,*

¹ Department of Biology, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, INF 364, 69120 Heidelberg, Germany

² Interfaculty Institute for Biochemistry, University of Tübingen, 72076 Tübingen, Germany

³ Max Planck Institute for Intelligent Systems, 70569 Stuttgart, Germany

⁴ Physical Chemistry of Biosystems, Institute of Physical Chemistry, Heidelberg University, 69120 Heidelberg, Germany

⁵ Institute for Toxicology and Genetics, Karlsruhe Institute for Technology, 76021 Karlsruhe, Germany

Molecules 2015, 20(11), 20146-20160; https://doi.org/10.3390/molecules201119682 - 9 Nov 2015

Cited by 72 | Viewed by 16069

Abstract

In the present investigation we studied the molecular mechanisms of the monodesmosidic saponin digitonin on natural and artificial membranes. We measured the hemolytic activity of digitonin on red blood cells (RBCs). Also different lipid membrane models (large unilamellar vesicles, LUVs, and giant unilamellar [...] Read more.

In the present investigation we studied the molecular mechanisms of the monodesmosidic saponin digitonin on natural and artificial membranes. We measured the hemolytic activity of digitonin on red blood cells (RBCs). Also different lipid membrane models (large unilamellar vesicles, LUVs, and giant unilamellar vesicles, GUVs) in the presence and absence of cholesterol were employed. The stability and permeability of the different vesicle systems were studied by using calcein release assay, GUVs membrane permeability assay using confocal microscopy (CM) and fluorescence correlation spectroscopy (FCS) and vesicle size measurement by dynamic light scattering (DLS). The results support the essential role of cholesterol in explaining how digitonin can disintegrate biological and artificial membranes. Digitonin induces membrane permeability or causes membrane rupturing only in the presence of cholesterol in an all-or-none mechanism. This effect depends on the concentrations of both digitonin and cholesterol. At low concentrations, digitonin induces membrane permeability while keeping the membrane intact. When digitonin is combined with other drugs, a synergistic potentiation can be observed because it facilitates their uptake. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 380 KiB

Open AccessArticle

New Sulphated Flavonoids from Wissadula periplocifolia (L.) C. Presl (Malvaceae)

by Yanna C. F. Teles¹, Carolina Campolina Rebello Horta^2,†, Maria De Fátima Agra^3,†, Weam Siheri^4,†, Marie Boyd^4,†, John O. Igoli^4,†, Alexander I. Gray^4,† and Maria De Fátima Vanderlei De Souza^1,*

¹ Post-Graduation Program in Development and Technological Innovation in Medicines, Health Sciences Center, Federal University of Paraiba, 58051-900 João Pessoa, PB, Brazil

² Capes Foundation, Ministry of Education of Brazil, Caixa Postal 250, 70359-970 Brasília, DF, Brazil

³ Biotechnology Center, Federal University of Paraiba, 58051-900 João Pessoa, PB, Brazil

⁴ Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, G4 0RE Glasgow, UK

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 20161-20172; https://doi.org/10.3390/molecules201119685 - 9 Nov 2015

Cited by 54 | Viewed by 8550

Abstract

Wissadula periplocifolia (L.) C. Presl (Malvaceae) is commonly used in Brazil to treat bee stings and as an antiseptic. The antioxidant properties of its extracts have been previously demonstrated, thus justifying a phytochemical investigation for its bioactive phenolic constituents. This has yielded five [...] Read more.

Wissadula periplocifolia (L.) C. Presl (Malvaceae) is commonly used in Brazil to treat bee stings and as an antiseptic. The antioxidant properties of its extracts have been previously demonstrated, thus justifying a phytochemical investigation for its bioactive phenolic constituents. This has yielded five new sulphated flavonoids: 8-O-sulphate isoscutellarein (yannin) (1a); 4′-O-methyl-7-O-sulphate isoscutellarein (beltraonin) (1b); 7-O-sulphate acacetin (wissadulin) (2a); 4′-O-methyl-8-O-sulphate isoscutellarein (caicoine) (2b) and 3′-O-methyl-8-O-sulphate hypolaetin (pedroin) (3b) along with the known flavonoids 7,4′-di-O-methyl-8-O-sulphate isoscutellarein (4), acacetin, apigenin, isoscutellarein, 4´-O-methyl isoscutellarein, 7,4′-di-O-methylisoscutellarein, astragalin and tiliroside. The compounds were isolated by column chromatography and identified by NMR (¹H, ¹³C, HMQC, HMBC and COSY) and LC-HRMS. A cell based assay was carried out to evaluate the preliminary cytotoxic properties of the flavonoids against UVW glioma and PC-3M prostate cancer cells as well as non-tumour cell lines. The obtained results showed that acacetin, tiliroside, a mixture of acacetin + apigenin and the sulphated flavonoids 2a + 2b exhibited inhibitory activity against at least one of the cell lines tested. Among the tested flavonoids acacetin and tiliroside showed lower IC₅₀ values, presenting promising antitumor effects. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 3167 KiB

Open AccessArticle

Glycosylated Metal Phthalocyanines

by Michael Hanack

Institut für Organische Chemie der, Universität Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany

Molecules 2015, 20(11), 20173-20185; https://doi.org/10.3390/molecules201119683 - 10 Nov 2015

Cited by 7 | Viewed by 7351

Abstract

In the first part; the syntheses of mono-; di-; and tetra-glycosylated phthalonitriles is described; which are the most used starting materials for the preparation of the corresponding glycosylated metal (mostly zinc) phthalocyanines. In the second section; the preparation of symmetric and unsymmetric mono-; [...] Read more.

In the first part; the syntheses of mono-; di-; and tetra-glycosylated phthalonitriles is described; which are the most used starting materials for the preparation of the corresponding glycosylated metal (mostly zinc) phthalocyanines. In the second section; the preparation of symmetric and unsymmetric mono-; tetra-; and octa- glycosylated zinc phthalocyanines are reviewed; in which the sugar is attached to the phthalocyanine macrocycle; either anomerically or via another one of its OH-groups. Full article

(This article belongs to the Special Issue Tetrapyrroles, Porphyrins and Phthalocyanines)

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9 pages, 2634 KiB

Open AccessArticle

Synthesis of Novel β-Keto-Enol Derivatives Tethered Pyrazole, Pyridine and Furan as New Potential Antifungal and Anti-Breast Cancer Agents

by Smaail Radi^1,*

, Said Tighadouini¹, Olivier Feron², Olivier Riant³, Mohammed Bouakka⁴, Redouane Benabbes⁴ and Yahia N. Mabkhot⁵

¹ Department of Chemistry, Faculty of Sciences, University Mohamed I, Oujda-60000, Morocco

² Angiogenesis and Cancer Research Lab, Pole of Pharmacology and Therapeutics-FATH5349, Institute of Experimental and Clinical Research, Université catholique de Louvain (UCL), Brussels 1200, Belgium

³ Molecules, Solids and Reactivity (MOST), Institute of Condensed Mater and Nanosciences (IMCN), Université catholique de Louvain (UCL), Place Louis Pasteur 1, Louvain-la-Neuve 1348, Belgium

⁴ Department of Biologie, Faculty of Sciences, University Mohamed I, Oujda-60000, Morocco

⁵ Department of Chemistry, Faculty of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia

Molecules 2015, 20(11), 20186-20194; https://doi.org/10.3390/molecules201119684 - 10 Nov 2015

Cited by 40 | Viewed by 9150

Abstract

Recently, a new generation of highly promising inhibitors bearing β-keto-enol functionality has emerged. Reported herein is the ﬁrst synthesis and use of novel designed drugs based on the β-keto-enol group embedded with heterocyclic moieties such as pyrazole, pyridine, and furan, prepared in a [...] Read more.

Recently, a new generation of highly promising inhibitors bearing β-keto-enol functionality has emerged. Reported herein is the ﬁrst synthesis and use of novel designed drugs based on the β-keto-enol group embedded with heterocyclic moieties such as pyrazole, pyridine, and furan, prepared in a one-step procedure by mixed Claisen condensation. All the newly synthesized compounds were characterized by FT-IR, ¹H-NMR, ¹³C-NMR, ESI/LC-MS, elemental analysis, and evaluated for their in vitro antiproliferative activity against breast cancer (MDA-MB241) human cell lines and fungal strains (Fusarium oxysporum f.sp albedinis FAO). Three of the synthesized compounds showed potent activity against fungal strains with IC₅₀ values in the range of 0.055–0.092 µM. The results revealed that these compounds showed better IC₅₀ values while compared with positive controls. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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11 pages, 3743 KiB

Open AccessArticle

Isomerization of Internal Alkynes to Iridium(III) Allene Complexes via C–H Bond Activation: Expanded Substrate Scope, and Progress towards a Catalytic Methodology

by Neha Phadke and Michael Findlater^*

Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA

Molecules 2015, 20(11), 20195-20205; https://doi.org/10.3390/molecules201119686 - 10 Nov 2015

Cited by 4 | Viewed by 9410

Abstract

The synthesis of a series of allene complexes (POCOP)Ir(η²-RC=^.=CR’) 1b–4b (POCOP = 2,6-bis(di-tert-butylphosphonito)benzene) via isomerization of internal alkynes is reported. We have demonstrated that the application of this methodology is viable for the isomerization of [...] Read more.

The synthesis of a series of allene complexes (POCOP)Ir(η²-RC=^.=CR’) 1b–4b (POCOP = 2,6-bis(di-tert-butylphosphonito)benzene) via isomerization of internal alkynes is reported. We have demonstrated that the application of this methodology is viable for the isomerization of a wide variety of alkyne substrates. Deuterium labeling experiments support our proposed mechanism. The structures of the allene complexes 1b–4b were determined using spectroscopic data analysis. Additionally, the solid-state molecular structure of complex 2b was determined using single crystal X-ray diffraction studies and it confirmed the assignment of an iridium-bound allene isomerization product. The rates of isomerization were measured using NMR techniques over a range of temperatures to allow determination of thermodynamic parameters. Finally, we report a preliminary step towards developing a catalytic methodology; the allene may be liberated from the metal center by exposure of the complex to an atmosphere of carbon monoxide. Full article

(This article belongs to the Special Issue C-H Bond Activation and Functionalization)

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13 pages, 3133 KiB

Open AccessArticle

Functional Analysis of the Isopentenyl Diphosphate Isomerase of Salvia miltiorrhiza via Color Complementation and RNA Interference

by Xianan Zhang^1,†, Hongyu Guan^1,†, Zhubo Dai², Juan Guo³, Ye Shen³, Guanghong Cui³, Wei Gao¹ and Luqi Huang^3,*

¹ School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China

² Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China

³ Institute of Chinese Materia Medica, Chinese Academy of Chinese Medical Sciences, Beijing 100700, China

^† These authors contributed equally.

Molecules 2015, 20(11), 20206-20218; https://doi.org/10.3390/molecules201119689 - 10 Nov 2015

Cited by 19 | Viewed by 7498

Abstract

Isopentenyl diphosphate isomerase (IPI) catalyzes the isomerization between the common terpene precursor substances isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) during the terpenoid biosynthesis process. In this study, tissue expression analysis revealed that the expression level of the Salvia miltiorrhiza IPI1 gene ( [...] Read more.

Isopentenyl diphosphate isomerase (IPI) catalyzes the isomerization between the common terpene precursor substances isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) during the terpenoid biosynthesis process. In this study, tissue expression analysis revealed that the expression level of the Salvia miltiorrhiza IPI1 gene (SmIPI1) was higher in the leaves than in the roots and stems. Furthermore, color complementation and RNA interference methods were used to verify the function of the SmIPI1 gene from two aspects. A recombinant SmIPI1 plasmid was successfully constructed and transferred into engineered E. coli for validating the function of SmIPI1 through the color difference in comparison to the control group; the observed color difference indicated that SmIPI1 served in promoting the accumulation of lycopene. Transformant hairy root lines with RNA interference of SmIPI1 were successfully constructed mediated by Agrobacterium rhizogenes ACCC 10060. RNA interference hairy roots had a severe phenotype characterized by withering, deformity or even death. The mRNA expression level of SmIPI1 in the RSi3 root line was only 8.4% of that of the wild type. Furthermore the tanshinone content was too low to be detected in the RNA interference lines. These results suggest that SmIPI1 plays a critical role in terpenoid metabolic pathways. Addition of an exogenous SmIPI1 gene promoted metabolic flow toward the biosynthesis of carotenoids in E. coli, and SmIPI1 interference in S. miltiorrhiza hairy roots may cause interruption of the 2-C-methyl-D-erythritol-4-phosphate metabolic pathway. Full article

(This article belongs to the Section Metabolites)

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11 pages, 5344 KiB

Open AccessArticle

Genetic Authentication of Gardenia jasminoides Ellis var. grandiflora Nakai by Improved RAPD-Derived DNA Markers

by Zhiqiang Mei^1,†, Boxu Zhou^1,†, Chunli Wei^1,2,†, Jingliang Cheng¹, Saber Imani^1,3, Hanchun Chen⁴ and Junjiang Fu^1,2,5,*

¹ Research Center for Preclinical Medicine, Sichuan Medical University, Luzhou 646000, China

² State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR) 999078, China

³ Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran 14359-44711, Iran

⁴ Department of Biochemistry, School of Life Sciences & the State Key Laboratory of Medical Genetics, Central South University, Changsha 410013, China

⁵ Judicial Authentication Center, Sichuan Medical University, Luzhou 646000, China

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 20219-20229; https://doi.org/10.3390/molecules201119687 - 10 Nov 2015

Cited by 13 | Viewed by 6419

Abstract

The evergreen shrub, Gardenia jasminoides Ellis var. grandiflora Nakai is one of the most popular garden-plants, with significant ornamental importance. Here, we have cloned improved random ampliﬁed polymorphic DNA (RAPD) derived fragments into T-vector, and developed sequence-characterized amplified region (SCAR) markers. These markers [...] Read more.

The evergreen shrub, Gardenia jasminoides Ellis var. grandiflora Nakai is one of the most popular garden-plants, with significant ornamental importance. Here, we have cloned improved random ampliﬁed polymorphic DNA (RAPD) derived fragments into T-vector, and developed sequence-characterized amplified region (SCAR) markers. These markers have been deposited in GenBank database with the accession numbers KP641310, KP641311, KP641312 and KP641313 respectively. The BLAST search of database confirmed the novelty of these markers. The four SCAR markers, namely ZZH11, ZZH31, ZZH41 and ZZH51 can specifically recognize the genetic materials of G. jasminoides from other plant species. Moreover, SCAR marker ZZH31 can be used to distinguish G. jasminoides Ellis var. grandiflora Nakai from other G. jasminoides on the market. Together, this study has developed four stably molecular SCAR markers by improved RAPD-derived DNA markers for the genetic identification and authentication, and for ecological conservation of medicinal and ornamental plant G. jasminoides. Full article

(This article belongs to the Section Molecular Diversity)

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10 pages, 5841 KiB

Open AccessArticle

Auraptene Acts as an Anti-Inflammatory Agent in the Mouse Brain

by Satoshi Okuyama¹, Mayu Morita¹, Miki Kaji¹, Yoshiaki Amakura², Morio Yoshimura², Koji Shimamoto¹, Yu Ookido¹, Mitsunari Nakajima¹ and Yoshiko Furukawa^1,*

¹ Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan

² Department of Pharmacognosy, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan

Molecules 2015, 20(11), 20230-20239; https://doi.org/10.3390/molecules201119691 - 10 Nov 2015

Cited by 43 | Viewed by 6687

Abstract

The anti-inflammatory activity of auraptene (AUR), a citrus coumarin, in peripheral tissues is well-known, and we previously demonstrated that AUR exerts anti-inflammatory effects in the ischemic brain; the treatment of mice with AUR for eight days immediately after ischemic surgery suppressed demise and [...] Read more.

The anti-inflammatory activity of auraptene (AUR), a citrus coumarin, in peripheral tissues is well-known, and we previously demonstrated that AUR exerts anti-inflammatory effects in the ischemic brain; the treatment of mice with AUR for eight days immediately after ischemic surgery suppressed demise and neuronal cell death in the hippocampus, possibly through its anti-inflammatory effects in the brain. We suggested that these effects were at least partly mediated by the suppression of inflammatory mediators derived from astrocytes. The present study showed that (1) AUR, as a pretreatment for five days before and another three days after ischemic surgery, suppressed microglial activation, cyclooxygenase (COX)-2 expression in astrocytes, and COX-2 mRNA expression in the hippocampus; (2) AUR suppressed the lipopolysaccharide-induced expression of COX-2 mRNA and the mRNA of pro-inflammatory cytokines in cultured astrocytes; (3) AUR was still detectable in the brain 60 min after its intraperitoneal administration. These results support our previous suggestion that AUR directly exerts anti-inflammatory effects on the brain. Full article

(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)

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14 pages, 2670 KiB

Open AccessArticle

Role of the Red Ginseng in Defense against the Environmental Heat Stress in Sprague Dawley Rats

by Kui-Jin Kim^1,†, Kye-Yoon Yoon^1,†, Hee-Do Hong² and Boo-Yong Lee^1,*

¹ Department of Food Science and Biotechnology, College of Life Science, CHA University, Kyonggi 463-400, Korea

² Korea Food Research Institute, Kyonggi, Seongnam 463-746, Korea

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 20240-20253; https://doi.org/10.3390/molecules201119692 - 10 Nov 2015

Cited by 21 | Viewed by 7921

Abstract

Global temperature change causes heat stress related disorders in humans. A constituent of red ginseng has been known the beneficial effect on the resistance to many diseases. However, the mechanism of red ginseng (RG) against heat stress still remains unclear. To determine the [...] Read more.

Global temperature change causes heat stress related disorders in humans. A constituent of red ginseng has been known the beneficial effect on the resistance to many diseases. However, the mechanism of red ginseng (RG) against heat stress still remains unclear. To determine the effect of RG on heat stress, we examined the effect of the RG on the gene expression profiles in rats subjected to environmental heat stress. We evaluated the transcripts associated with hepatic lipid accumulation and oxidative stress in rats subjected to heat stress. We also analyzed the reactive oxygen species (ROS) contents. Our results suggested RG inhibited heat stress mediated altering mRNA expressions include HSPA1, DEAF1, HMGCR, and FMO1. We also determined RG attenuated fat accumulation in the liver by altering C/EBPβ expression. RG promoted to repress the heat stress mediated hepatic cell death by inhibiting of Bcl-2 expression in rats subjected to heat stress. Moreover, RG administered group during heat stress dramatically decreased the malondialdehyde (MDA) contents and ROS associated genes compared with the control group. Thus, we suggest that RG might influence inhibitory effect on environmental heat stress induced abnormal conditions in humans. Full article

(This article belongs to the Collection Herbal Medicine Research)

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14 pages, 1042 KiB

Open AccessArticle

Molecular Cloning, Expression Pattern and Genotypic Effects on Glucoraphanin Biosynthetic Related Genes in Chinese Kale (Brassica oleracea var. alboglabra Bailey)

by Ling Yin, Changming Chen, Guoju Chen, Bihao Cao and Jianjun Lei^*

Department of Hortscience, South China Agricultural University, Guangzhou 510642, China

Molecules 2015, 20(11), 20254-20267; https://doi.org/10.3390/molecules201119688 - 11 Nov 2015

Cited by 9 | Viewed by 6611

Abstract

Glucoraphanin is a plant secondary metabolite that is involved in plant defense and imparts health-promoting properties to cruciferous vegetables. In this study, three genes involved in glucoraphanin metabolism, branched-chain aminotransferase 4 (BCAT4), methylthioalkylmalate synthase 1 (MAM1) and dihomomethionine N-hydroxylase [...] Read more.

Glucoraphanin is a plant secondary metabolite that is involved in plant defense and imparts health-promoting properties to cruciferous vegetables. In this study, three genes involved in glucoraphanin metabolism, branched-chain aminotransferase 4 (BCAT4), methylthioalkylmalate synthase 1 (MAM1) and dihomomethionine N-hydroxylase (CYP79F1), were cloned from Chinese kale (Brassica oleracea var. alboglabra Bailey). Sequence homology and phylogenetic analysis identified these genes and confirmed the evolutionary status of Chinese kale. The transcript levels of BCAT4, MAM1 and CYP79F1 were higher in cotyledon, leaf and stem compared with flower and silique. BCAT4, MAM1 and CYP79F1 were expressed throughout leaf development with lower transcript levels during the younger stages. Glucoraphanin content varied extensively among different varieties, which ranged from 0.25 to 2.73 µmol·g⁻¹ DW (dry weight). Expression levels of BCAT4 and MAM1 were high at vegetative–reproductive transition phase, while CYP79F1 was expressed high at reproductive phase. BCAT4, MAM1 and CYP79F1 were expressed significantly high in genotypes with high glucoraphanin content. All the results provided a better understanding of the roles of BCAT4, MAM1 and CYP79F1 in the glucoraphanin biosynthesis of Chinese kale. Full article

(This article belongs to the Section Molecular Diversity)

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1 pages, 334 KiB

Open AccessCorrection

Correction: Wang L.K., et al. Two New Lanostane Triterpenoids from the Branches and Leaves of Polyalthia oblique. Molecules 2014, 19, 7621–7628

by Liu-Kai Wang^†, Cai-Juan Zheng^†, Xiao-Bao Li, Guang-Ying Chen, Chang-Ri Han, Wen-Hao Chen and Xiao-Ping Song^*

¹ Key Laboratory of Tropical Medicinal Plant Chemistry of Ministry of Education, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou 571158, Hainan, China

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 20268; https://doi.org/10.3390/molecules201119690 - 11 Nov 2015

Cited by 1 | Viewed by 4765

Abstract

The authors wish to make the following correction to their paper [1], published recently in Molecules. [...] Full article

(This article belongs to the Collection Bioactive Compounds)

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17 pages, 1977 KiB

Open AccessArticle

Evaluation of the Cytotoxicity of α-Cyclodextrin Derivatives on the Caco-2 Cell Line and Human Erythrocytes

by Eszter Róka^1,2, Zoltán Ujhelyi¹, Mária Deli³, Alexandra Bocsik³, Éva Fenyvesi⁴, Lajos Szente⁴, Ferenc Fenyvesi¹, Miklós Vecsernyés¹, Judit Váradi¹, Pálma Fehér¹, Rudolf Gesztelyi⁵

, Caroline Félix², Florent Perret² and Ildikó Katalin Bácskay^1,*

¹ Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei körút 98, Debrecen H-4032, Hungary

² University Lyon 1, ICBMS, Equipe CSAp, 43 Boulevard du 11 Novembre 1918, Villeurbanne F-69622, France

³ Department of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Temesvári körút 62, Szeged H-6726, Hungary

⁴ Cyclolab Ltd., Illatos út 7, Budapest H-1097, Hungary

⁵ Department of Pharmacology and Pharmacodynamics, Faculty of Pharmacy, University of Debrecen, Nagyerdei körút 98, Debrecen H-4032, Hungary

Molecules 2015, 20(11), 20269-20285; https://doi.org/10.3390/molecules201119694 - 11 Nov 2015

Cited by 62 | Viewed by 8600

Abstract

Cyclodextrins, even the 6-membered α-cyclodextrin, are approved in the various pharmacopoeias as pharmaceutical excipients for solubilizing and stabilizing drugs as well as for controlling drug release. Recently α-cyclodextrin has also been marketed as health food with beneficial effects on blood lipid profiles. However, [...] Read more.

Cyclodextrins, even the 6-membered α-cyclodextrin, are approved in the various pharmacopoeias as pharmaceutical excipients for solubilizing and stabilizing drugs as well as for controlling drug release. Recently α-cyclodextrin has also been marketed as health food with beneficial effects on blood lipid profiles. However, the concentration of α-cyclodextrin used may be very high in these cases, and its toxic attributes have to be seriously considered. The objective of this study was to investigate the cytotoxicity of various, differently substituted α-cyclodextrin derivatives and determine relationship between the structures and cytotoxicity. Three different methods were used, viability tests (MTT assay and Real Time Cell Electronic Sensing on Caco-2 cells) as well as hemolysis test on human red blood cells. The effect of α-cyclodextrin derivatives resulted in concentration-dependent cytotoxicity, so the IC50 values have been determined. Based on our evaluation, the Real Time Cell Electronic Sensing method is the most accurate for describing the time and concentration dependency of the observed toxic effects. Regarding the cytotoxicity on Caco-2 cells, phosphatidylcholine extraction may play a main role in the mechanism. Our results should provide help in selecting those α-cyclodextrin derivatives which have the potential of being used safely in medical formulations. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 2349 KiB

Open AccessArticle

β–Cyclodextrin–Propyl Sulfonic Acid Catalysed One-Pot Synthesis of 1,2,4,5-Tetrasubstituted Imidazoles as Local Anesthetic Agents

by Yan Ran^1,†, Ming Li^2,† and Zong-Ze Zhang^1,*

¹ Zhongnan Hospital of Wuhan University, Department of Anesthesiology, Wuhan University, Wuhan 430071, China

² Department of Doppler Ultrasound, PLA421 Hospital, Guangzhou 510318, China

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 20286-20296; https://doi.org/10.3390/molecules201119696 - 12 Nov 2015

Cited by 17 | Viewed by 7154

Abstract

Some functionalized 1,2,4,5-tetrasubstituted imidazole derivatives were synthesized using a one-pot, four component reaction involving 1,2-diketones, aryl aldehydes, ammonium acetate and substituted aromatic amines. The synthesis has been efficiently carried out in a solvent free medium using β-cyclodextrin-propyl sulfonic acid as a catalyst to [...] Read more.

Some functionalized 1,2,4,5-tetrasubstituted imidazole derivatives were synthesized using a one-pot, four component reaction involving 1,2-diketones, aryl aldehydes, ammonium acetate and substituted aromatic amines. The synthesis has been efficiently carried out in a solvent free medium using β-cyclodextrin-propyl sulfonic acid as a catalyst to afford the target compounds in excellent yields. The local anesthetic effect of these derivatives was assessed in comparison to lidocaine as a standard using a rabbit corneal and mouse tail anesthesia model. The three most potent promising compounds were subjected to a rat sciatic nerve block assay where they showed considerable local anesthetic activity, along with minimal toxicity. Among the tested analogues, 4-(1-benzyl-4,5-diphenyl-1H-imidazol-2-yl)-N,N-dimethylaniline (5g) was identified as most potent analogue with minimal toxicity. It was further characterized by a more favourable therapeutic index than the standard. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 2643 KiB

Open AccessArticle

Derinat Protects Skin against Ultraviolet-B (UVB)-Induced Cellular Damage

by Wen-Li Hsu^1,2, Jian-He Lu³, Mami Noda⁴, Ching-Ying Wu^3,5, Jia-dai Liu⁴, Manabu Sakakibara⁶, Ming-Hsien Tsai^2,3, Hsin-Su Yu^5,7, Ming-Wei Lin^8,9

, Yaw-Bin Huang^8,9, Shian-Jang Yan^1,10,* and Tohru Yoshioka^2,3,*

¹ The Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan

² Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

³ Graduate Institute of Medicine, School of Medicine, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan

⁴ Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8581, Japan

⁵ Department of Dermatology, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan

⁶ School of High-Technology for Human Welfare, Tokai University, 410-0321 Numazu, Shizuoka, Japan

⁷ National Health Research Institutes, Distinguished Investigator, National Environmental Health Research Center, No. 35, Keyan Road, Zhunan Town, Miaoli County 35053, Taiwan

⁸ School of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

⁹ Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

¹⁰ Department of Physiology, College of Medicine, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan

Molecules 2015, 20(11), 20297-20311; https://doi.org/10.3390/molecules201119693 - 12 Nov 2015

Cited by 22 | Viewed by 11222

Abstract

Ultraviolet-B (UVB) is one of the most cytotoxic and mutagenic stresses that contribute to skin damage and aging through increasing intracellular Ca²⁺ and reactive oxygen species (ROS). Derinat (sodium deoxyribonucleate) has been utilized as an immunomodulator for the treatment of ROS-associated diseases [...] Read more.

Ultraviolet-B (UVB) is one of the most cytotoxic and mutagenic stresses that contribute to skin damage and aging through increasing intracellular Ca²⁺ and reactive oxygen species (ROS). Derinat (sodium deoxyribonucleate) has been utilized as an immunomodulator for the treatment of ROS-associated diseases in clinics. However, the molecular mechanism by which Derinat protects skin cells from UVB-induced damage is poorly understood. Here, we show that Derinat significantly attenuated UVB-induced intracellular ROS production and decreased DNA damage in primary skin cells. Furthermore, Derinat reduced intracellular ROS, cyclooxygenase-2 (COX-2) expression and DNA damage in the skin of the BALB/c-nu mice exposed to UVB for seven days in vivo. Importantly, Derinat blocked the transient receptor potential canonical (TRPC) channels (TRPCs), as demonstrated by calcium imaging. Together, our results indicate that Derinat acts as a TRPCs blocker to reduce intracellular ROS production and DNA damage upon UVB irradiation. This mechanism provides a potential new application of Derinat for the protection against UVB-induced skin damage and aging. Full article

(This article belongs to the Collection Bioactive Compounds)

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8 pages, 2083 KiB

Open AccessArticle

Cytotoxic Activities, SAR and Anti-Invasion Effects of Butylphthalide Derivatives on Human Hepatocellular Carcinoma SMMC7721 Cells

by Yihan Hu¹, Xiaoxu Bi², Pu Zhao², Huachuan Zheng³ and Xueshi Huang^1,2,*

¹ Laboratory of Metabolic Disease Research and Drug Development, China Medical University, Shenyang 110001, China

² Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China

³ Cancer Research Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, the First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001, China

Molecules 2015, 20(11), 20312-20319; https://doi.org/10.3390/molecules201119699 - 12 Nov 2015

Cited by 12 | Viewed by 6269

Abstract

A series of butylphthalide derivatives (BPDs) 1–8 were isolated from the extract of the dried rhizome of Ligusticum chuanxiong Hort. (Umbelliferae). The cytotoxic activities of BPDs 1–8 were evaluated using a panel of human cancer cell lines. In addition, [...] Read more.

A series of butylphthalide derivatives (BPDs) 1–8 were isolated from the extract of the dried rhizome of Ligusticum chuanxiong Hort. (Umbelliferae). The cytotoxic activities of BPDs 1–8 were evaluated using a panel of human cancer cell lines. In addition, the SAR analysis and potential anti-invasion activities were investigated. The sp² carbons at C-7 and C-7a appeared to be essential for the cytotoxic activities of BPDs. BPDs 5 and 6 remarkably inhibited the migration and invasion of cancer cells. The anti-invasion activity of dimer 6 was demonstrated to be significantly higher than monomer 5. Full article

(This article belongs to the Collection Bioactive Compounds)

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14 pages, 1748 KiB

Open AccessArticle

Enhancement of Palmarumycin C₁₂ and C₁₃ Production by the Endophytic Fungus Berkleasmium sp. Dzf12 in an Aqueous-Organic Solvent System

by Yan Mou¹, Dan Xu¹, Ziling Mao¹, Xuejiao Dong¹, Fengke Lin¹, Ali Wang¹, Daowan Lai¹

, Ligang Zhou^1,*

and Bingyan Xie^2,*

¹ Department of Plant Pathology, College of Agronomy and Biotechnology, China Agronomy and Biotechnology, Beijing 100193, China

² Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing 100081, China

Molecules 2015, 20(11), 20320-20333; https://doi.org/10.3390/molecules201119700 - 12 Nov 2015

Cited by 6 | Viewed by 6133

Abstract

The endophytic fungus Berkleasmium sp. Dzf12, isolated from Dioscorea zingiberensis, was found to produce palmarumycins C₁₂ and C₁₃ which possess a great variety of biological activities. Seven biocompatible water-immiscible organic solvents including n-dodecane, n-hexadecane, 1-hexadecene, liquid paraffin, dibutyl [...] Read more.

The endophytic fungus Berkleasmium sp. Dzf12, isolated from Dioscorea zingiberensis, was found to produce palmarumycins C₁₂ and C₁₃ which possess a great variety of biological activities. Seven biocompatible water-immiscible organic solvents including n-dodecane, n-hexadecane, 1-hexadecene, liquid paraffin, dibutyl phthalate, butyl oleate and oleic acid were evaluated to improve palmarumycins C₁₂ and C₁₃ production in suspension culture of Berkleasmium sp. Dzf12. Among the chosen solvents both butyl oleate and liquid paraffin were the most effective to improve palmarumycins C₁₂and C₁₃ production. The addition of dibutyl phthalate, butyl oleate and oleic acid to the cultures of Berkleasmium sp. Dzf12 significantly enhanced palmarumycin C₁₂ production by adsorbing palmarumycin C₁₂ into the organic phase. When butyl oleate was fed at 5% (v/v) in medium at the beginning of fermentation (day 0), the highest palmarumycin C₁₂ yield (191.6 mg/L) was achieved, about a 34.87-fold increase in comparison with the control (5.3 mg/L). n-Dodecane, 1-hexadecene and liquid paraffin had a great influence on the production of palmarumycin C₁₃. When liquid paraffin was added at 10% (v/v) in medium on day 3 of fermentation, the palmarumycin C₁₃ yield reached a maximum value (134.1 mg/L), which was 4.35-fold that of the control (30.8 mg/L). Application of the aqueous-organic solvent system should be a simple and efficient process strategy for enhancing palmarumycin C₁₂ and C₁₃ production in liquid cultures of the endophytic fungus Berkleasmium sp. Dzf12. Full article

(This article belongs to the Section Natural Products Chemistry)

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7 pages, 639 KiB

Open AccessCommunication

Triterpenoids from the Herbs of Salicornia bigelovii

by Yu Shan^1,2, Huan Li¹, Fuqin Guan¹, Yu Chen¹, Min Yin¹, Ming Wang¹, Xu Feng¹ and Qizhi Wang^1,*

¹ Jiangsu Key Laboratory for Bioresources of Saline Soils, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China

² Jiangsu Provincial Platform for Conservation and Utilization of Agricultural Germplasm, Nanjing 210014, China

Molecules 2015, 20(11), 20334-20340; https://doi.org/10.3390/molecules201119695 - 12 Nov 2015

Cited by 12 | Viewed by 6511

Abstract

A new nortriterpene saponin, 3-O-β-d-glucuronopyranosyl-30-norolean-12,20(29)-dien-23- oxo-28-oic acid, namely bigelovii D (11), was isolated from the hydroalcoholic extract of herbs of Salicornia bigelovii along with 10 known saponins (1–10). Their chemical structures were identified on the [...] Read more.

A new nortriterpene saponin, 3-O-β-d-glucuronopyranosyl-30-norolean-12,20(29)-dien-23- oxo-28-oic acid, namely bigelovii D (11), was isolated from the hydroalcoholic extract of herbs of Salicornia bigelovii along with 10 known saponins (1–10). Their chemical structures were identified on the basis of spectroscopic analyses including two-dimensional NMR and a comparison with literature data. Some of these compounds showed potent antifungal activities in vitro. Compounds 3, 4, 5, 6, 7, 10 and 11 demonstrated potent inhibitory activities against Colletotrichum gloeosporioides and compound 11 displayed broad-spectrum inhibitory activity against Alternaria alternata, A. solani, Botrytis cinerea, C. gloeosporioides, Fusarium graminearum, F. verticilloides, Thanatephorus cucumeris and Sclerotinia sclerotiorum, with EC₅₀ values ranging from 13.6 to 36.3 μg/mL. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 1839 KiB

Open AccessArticle

Direct Aminolysis of Ethoxycarbonylmethyl 1,4-Dihydropyridine-3-carboxylates

by Brigita Vigante^*, Martins Rucins, Aiva Plotniece

, Karlis Pajuste, Iveta Luntena, Brigita Cekavicus, Egils Bisenieks, Rufus Smits, Gunars Duburs and Arkadij Sobolev

Latvian Institute of Organic Synthesis, Aizkraukles str. 21, Riga LV-1006, Latvia

Molecules 2015, 20(11), 20341-20354; https://doi.org/10.3390/molecules201119697 - 12 Nov 2015

Cited by 8 | Viewed by 9233

Abstract

The ethoxycarbonylmethyl esters of 1,4-dihydropyridines were directly converted into carbamoylmethyl esters in the presence of 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) in good to excellent yields under mild conditions. The use of TBD is crucial for the successful aminolysis of ethoxycarbonylmethyl ester of 1,4-dihydropyridines with secondary amines [...] Read more.

The ethoxycarbonylmethyl esters of 1,4-dihydropyridines were directly converted into carbamoylmethyl esters in the presence of 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) in good to excellent yields under mild conditions. The use of TBD is crucial for the successful aminolysis of ethoxycarbonylmethyl ester of 1,4-dihydropyridines with secondary amines as without it the reaction does not proceed at all. The aminolysis reaction proceeded regioselectively, as the alkyl ester conjugated with the 1,4-dihydropyridine cycle was not involved in the reaction. Screening of other N-containing bases, such as triethylamine (TEA), pyridine, 4-(N,N-dimethylamino)pyridine (DMAP), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), imidazole, tetramethyl guanidine (TMG) and 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) as catalysts revealed no activity in the studied reaction. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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26 pages, 1694 KiB

Open AccessReview

α-Linolenic Acid, A Nutraceutical with Pleiotropic Properties That Targets Endogenous Neuroprotective Pathways to Protect against Organophosphate Nerve Agent-Induced Neuropathology

by Tetsade Piermartiri¹, Hongna Pan², Taiza H. Figueiredo³ and Ann M. Marini^2,*

¹ Molecular and Cellular Biology Graduate School Program, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA

² Department of Neurology and Program in Neuroscience, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA

³ Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA

Molecules 2015, 20(11), 20355-20380; https://doi.org/10.3390/molecules201119698 - 12 Nov 2015

Cited by 33 | Viewed by 10434

Abstract

α-Linolenic acid (ALA) is a nutraceutical found in vegetable products such as flax and walnuts. The pleiotropic properties of ALA target endogenous neuroprotective and neurorestorative pathways in brain and involve the transcription factor nuclear factor kappa B (NF-κB), brain-derived neurotrophic factor (BDNF), a [...] Read more.

α-Linolenic acid (ALA) is a nutraceutical found in vegetable products such as flax and walnuts. The pleiotropic properties of ALA target endogenous neuroprotective and neurorestorative pathways in brain and involve the transcription factor nuclear factor kappa B (NF-κB), brain-derived neurotrophic factor (BDNF), a major neuroprotective protein in brain, and downstream signaling pathways likely mediated via activation of TrkB, the cognate receptor of BDNF. In this review, we discuss possible mechanisms of ALA efficacy against the highly toxic OP nerve agent soman. Organophosphate (OP) nerve agents are highly toxic chemical warfare agents and a threat to military and civilian populations. Once considered only for battlefield use, these agents are now used by terrorists to inflict mass casualties. OP nerve agents inhibit the critical enzyme acetylcholinesterase (AChE) that rapidly leads to a cholinergic crisis involving multiple organs. Status epilepticus results from the excessive accumulation of synaptic acetylcholine which in turn leads to the overactivation of muscarinic receptors; prolonged seizures cause the neuropathology and long-term consequences in survivors. Current countermeasures mitigate symptoms and signs as well as reduce brain damage, but must be given within minutes after exposure to OP nerve agents supporting interest in newer and more effective therapies. The pleiotropic properties of ALA result in a coordinated molecular and cellular program to restore neuronal networks and improve cognitive function in soman-exposed animals. Collectively, ALA should be brought to the clinic to treat the long-term consequences of nerve agents in survivors. ALA may be an effective therapy for other acute and chronic neurodegenerative disorders. Full article

(This article belongs to the Collection Neuroprotection Mediated by Natural Products and Their Chemical Derivatives)

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10 pages, 2530 KiB

Open AccessArticle

Nonprenylated Xanthones from Gentiana lutea, Frasera caroliniensis, and Centaurium erythraea as Novel Inhibitors of Vascular Smooth Muscle Cell Proliferation

by Birgit Waltenberger^1,†, Rongxia Liu^2,3,†, Atanas G. Atanasov^2,*

, Stefan Schwaiger¹

, Elke H. Heiss², Verena M. Dirsch² and Hermann Stuppner^1,*

¹ Institute of Pharmacy/Pharmacognosy, University of Innsbruck, 6020 Innsbruck, Austria

² Department of Pharmacognosy, University of Vienna, 1090 Vienna, Austria

³ School of Pharmacy, Yantai University, 264005 Yantai, China

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 20381-20390; https://doi.org/10.3390/molecules201119703 - 13 Nov 2015

Cited by 22 | Viewed by 7657

Abstract

Aberrant proliferation of vascular smooth muscle cells (VSMC) plays a major role in restenosis, the pathological renarrowing of the blood vessel lumen after surgical treatment of stenosis. Since available anti-proliferative pharmaceuticals produce unfavorable side effects, there is high demand for the identification of [...] Read more.

Aberrant proliferation of vascular smooth muscle cells (VSMC) plays a major role in restenosis, the pathological renarrowing of the blood vessel lumen after surgical treatment of stenosis. Since available anti-proliferative pharmaceuticals produce unfavorable side effects, there is high demand for the identification of novel VSMC proliferation inhibitors. A natural product screening approach using a resazurin conversion assay enabled the identification of gentisin (1) from Gentiana lutea as a novel inhibitor of VSMC proliferation with an IC₅₀ valueof 7.84 µM. Aiming to identify further anti-proliferative compounds, 13 additional nonprenylated xanthones, isolated from different plant species, were also tested. While some compounds showed no or moderate activity at 30 µM, 1-hydroxy-2,3,4,5-tetramethoxyxanthone (4), swerchirin (6), and methylswertianin (7) showed IC₅₀ values between 10.2 and 12.5 µM. The anti-proliferative effect of 1, 4, 6, and 7 was confirmed by the quantification of DNA synthesis (BrdU incorporation) in VSMC. Cell death quantification (determined by LDH release in the culture medium) revealed that the compounds are not cytotoxic in the investigated concentration range. In conclusion, nonprenylated xanthones are identified as novel, non-toxic VSMC proliferation inhibitors, which might contribute to the development of new therapeutic applications to combat restenosis. Full article

(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)

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6 pages, 1061 KiB

Open AccessCommunication

Temporal Variation of Aristolochia chilensis Aristolochic Acids during Spring

by Rocío Santander^*, Alejandro Urzúa^*, Ángel Olguín and María Sánchez

Facultad de Química y Biología, Universidad de Santiago de Chile, Casilla 40, Correo 33, Santiago 9170022, Chile

Molecules 2015, 20(11), 20391-20396; https://doi.org/10.3390/molecules201119704 - 13 Nov 2015

Cited by 6 | Viewed by 4695

Abstract

In this communication, we report the springtime variation of the composition of aristolochic acids (AAs) in Aristolochia chilensis leaves and stems. The dominant AA in the leaves of all samples, which were collected between October and December, was AA-I (1), and [...] Read more.

In this communication, we report the springtime variation of the composition of aristolochic acids (AAs) in Aristolochia chilensis leaves and stems. The dominant AA in the leaves of all samples, which were collected between October and December, was AA-I (1), and its concentration varied between 212.6 ± 3.8 and 145.6 ± 1.2 mg/kg and decreased linearly. This decrease occurred in parallel with the increase in AA-Ia (5) concentration from 15.9 ± 0.8 mg/kg at the beginning of October to 96.8 ± 7.8 mg/kg in mid-December. Both acids are enzymatically related by methylation-demethylation reactions. Other AAs also showed important variations: AA-II (2) significantly increased in concentration, reaching a maximum in the first two weeks of November and subsequently decreasing in mid-December to approximately the October levels. The principal component in the AA mixture of the stems was also AA-I (1); similar to AA-II (2), its concentration increased beginning in October, peaked in the second week of November and subsequently decreased. The concentrations of AA-IIIa (6) and AA-IVa (7) in the leaves and stems varied throughout the study period, but no clear pattern was identified. Based on the variation of AAs in A. chilensis leaves and stems during the study period, the reduced contents of non-phenolic AAs and increased concentrations of phenolic AAs are likely associated with a decrease in this plant’s toxicity during the spring. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 771 KiB

Open AccessReview

Hydrogel-Based Drug Delivery Systems for Poorly Water-Soluble Drugs

by Matthew McKenzie, David Betts, Amy Suh, Kathryn Bui, London Doyoung Kim and Hyunah Cho^*

Pharmaceutical and Administrative Sciences, St. Louis College of Pharmacy, 4588 Parkview Place, St. Louis, MO 63110, USA

Molecules 2015, 20(11), 20397-20408; https://doi.org/10.3390/molecules201119705 - 13 Nov 2015

Cited by 189 | Viewed by 15573

Abstract

Hydrogels are three-dimensional materials that can withstand a great amount of water incorporation while maintaining integrity. This allows hydrogels to be very unique biomedical materials, especially for drug delivery. Much effort has been made to incorporate hydrophilic molecules in hydrogels in the field [...] Read more.

Hydrogels are three-dimensional materials that can withstand a great amount of water incorporation while maintaining integrity. This allows hydrogels to be very unique biomedical materials, especially for drug delivery. Much effort has been made to incorporate hydrophilic molecules in hydrogels in the field of drug delivery, while loading of hydrophobic drugs has not been vastly studied. However, in recent years, research has also been conducted on incorporating hydrophobic molecules within hydrogel matrices for achieving a steady release of drugs to treat various ailments. Here, we summarize the types of hydrogels used as drug delivery vehicles, various methods to incorporate hydrophobic molecules in hydrogel matrices, and the potential therapeutic applications of hydrogels in cancer. Full article

(This article belongs to the Collection Poorly Soluble Drugs)

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17 pages, 799 KiB

Open AccessArticle

Sensitive and Rapid UHPLC-MS/MS for the Analysis of Tomato Phenolics in Human Biological Samples

by Miriam Martínez-Huélamo^1,2, Sara Tulipani³, Olga Jáuregui⁴, Palmira Valderas-Martinez^2,5, Anna Vallverdú-Queralt^2,6, Ramón Estruch^2,5, Xavier Torrado¹ and Rosa M. Lamuela-Raventós^1,2,*

¹ Department of Nutrition and Food Science-XARTA-INSA, School of Pharmacy, University of Barcelona, Barcelona 08028, Spain

² Centre for Biomedical Network Research on the Pathophysiology of Obesity and Nutrition (CIBEROBN). Carlos III Health Institute, Madrid 28029, Spain

³ Biomedical Research Institute (IBIMA), Service of Endocrinology and Nutrition, Hospital Virgen de la Victoria, Teatinos Campus, University of Malaga, Malaga 29010, Spain

⁴ Scientific and Technological Centers of the University of Barcelona (CCiTUB), Barcelona 08028, Spain

⁵ Department of Internal Medicine, Hospital Clinic, Institute of Biomedical Investigation August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona 08036, Spain

⁶ INRA, UMR1083 Sciences for Oenology, 2 place Pierre Viala, Montpellier Cedex 34060, France

Molecules 2015, 20(11), 20409-20425; https://doi.org/10.3390/molecules201119702 - 16 Nov 2015

Cited by 17 | Viewed by 8902

Abstract

An UHPLC-MS/MS method for the quantification of tomato phenolic metabolites in human fluids was optimized and validated, and then applied in a pilot dietary intervention study with healthy volunteers. A 5-fold gain in speed (3.5 min of total run); 7-fold increase in MS [...] Read more.

An UHPLC-MS/MS method for the quantification of tomato phenolic metabolites in human fluids was optimized and validated, and then applied in a pilot dietary intervention study with healthy volunteers. A 5-fold gain in speed (3.5 min of total run); 7-fold increase in MS sensitivity and 2-fold greater efficiency (50% peak width reduction) were observed when comparing the proposed method with the reference-quality HPLC-MS/MS system, whose assay performance has been previously documented. The UHPLC-MS/MS method led to an overall improvement in the limits of detection (LOD) and quantification (LOQ) for all the phenolic compounds studied. The recoveries ranged between 68% and 100% in urine and 61% and 100% in plasma. The accuracy; intra- and interday precision; and stability met with the acceptance criteria of the AOAC International norms. Due to the improvements in the analytical method; the total phenolic metabolites detected in plasma and urine in the pilot intervention study were 3 times higher than those detected by HPLC-MS/MS. Comparing with traditional methods; which require longer time of analysis; the methodology described is suitable for the analysis of phenolic compounds in a large number of plasma and urine samples in a reduced time frame. Full article

(This article belongs to the Special Issue Recent Advances in Plant Phenolics)

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8 pages, 739 KiB

Open AccessArticle

Essential Oil Composition, Antioxidant, Cytotoxic and Antiviral Activities of Teucrium pseudochamaepitys Growing Spontaneously in Tunisia

by Saoussen Hammami^1,*, Habib Jmii², Ridha El Mokni³, Abdelbaki Khmiri¹, Khaled Faidi¹, Hatem Dhaouadi¹, Mohamed Hédi El Aouni³, Mahjoub Aouni² and Rajesh K. Joshi⁴

¹ Research Unit Applied Chemistry and Environment 13ES63, Faculty of Sciences of Monastir, Monastir University, 5000 Monastir, Tunisia

² Laboratory of Transmissible Diseases and Biologically Active Substances LR99ES27, Faculty of Pharmacy of Monastir, Avenue Avicenne, 5000 Monastir, Tunisia

³ Laboratory of Botany and Plant Ecology, Faculty of Sciences, University of Bizerta, Jarzouna, 7021 Bizerta, Tunisia

⁴ Department of Phytochemistry, Regional Medical Research Centre (Indian Council of Medical Research), Belgaum, Karnataka-590010, India

Molecules 2015, 20(11), 20426-20433; https://doi.org/10.3390/molecules201119707 - 16 Nov 2015

Cited by 55 | Viewed by 9491

Abstract

The chemical composition, antioxidant, cytotoxic and antiviral activities of the essential oil obtained by hydrodistillation from the aerial parts of Teucrium pseudochamaepitys (Lamiaceae) collected from Zaghouan province of Tunisia are reported. The essential oil was analyzed by gas chromatography equipped with a flame [...] Read more.

The chemical composition, antioxidant, cytotoxic and antiviral activities of the essential oil obtained by hydrodistillation from the aerial parts of Teucrium pseudochamaepitys (Lamiaceae) collected from Zaghouan province of Tunisia are reported. The essential oil was analyzed by gas chromatography equipped with a flame ionization detector (GC-FID) and gas chromatography coupled with mass spectrometry (GC/MS). Thirty-one compounds were identified representing 88.6% of the total essential oil. Hexadecanoic acid was found to be the most abundant component (26.1%) followed by caryophyllene oxide (6.3%), myristicin (4.9%) and α-cubebene (3.9%). The antioxidant capacity of the oil was measured on the basis of the scavenging activity to the stable 2,2-diphenyl-1-picrylhydrazyl (DPPH). The IC₅₀ value of the oil was evaluated as 0.77 mg·mL⁻¹. In addition, the essential oil was found to possess moderate cytotoxic effects on the HEp-2 cell line (50% cytotoxic concentration (CC₅₀) = 653.6 µg·mL⁻¹). The potential antiviral effect was tested against Coxsackievirus B (CV-B), a significant human and mouse pathogen that causes pediatric central nervous system disease, commonly with acute syndromes. The reduction of viral infectivity by the essential oil was measured using a cytopathic (CPE) reduction assay. Full article

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

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14 pages, 1396 KiB

Open AccessArticle

Synthesis and Antimicrobial Evaluation of a New Series of Heterocyclic Systems Bearing a Benzosuberone Scaffold

by Osama I. Abd El-Salam¹, Ali S. Alsayed², Korany A. Ali¹, Ahmed A. Abd Elwahab¹, Abd El-Galil E. Amr^3,* and Hassan M. Awad^4,5

¹ Applied Organic Chemistry Department, National Research Centre, Dokki, Giza 12622, Egypt

² Chemistry Department, Al-Azhar University, Nasr City, Cairo 1435, Egypt

³ Department of Pharmaceutical Chemistry, Drug Exploration & Development Chair, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

⁴ Chemistry of Natural and Microbial Products Department, Pharmaceutical Industries Division, National Research Centre, 33 El Buhouth St. (Former El Tahrir St.), Dokki, Giza 12622, Egypt

⁵ Deanship of Preparatory Year, Al jouf University, AL Jouf, Skaka 2014, Saudi Arabia

Molecules 2015, 20(11), 20434-20447; https://doi.org/10.3390/molecules201119701 - 16 Nov 2015

Cited by 10 | Viewed by 6195

Abstract

A series of novel benzosuberone derivatives were synthesized and evaluated as antimicrobial agents by using substituted benzosuberone derivatives 1a,b as starting materials. Treatment of 1a,b with phenyl isothiocyanate in dimethylformamide was followed by treatment with cold HCl solution to [...] Read more.

A series of novel benzosuberone derivatives were synthesized and evaluated as antimicrobial agents by using substituted benzosuberone derivatives 1a,b as starting materials. Treatment of 1a,b with phenyl isothiocyanate in dimethylformamide was followed by treatment with cold HCl solution to afford the thioamides 4a,b, which was reacted with methyl iodide to obtain methylated products 5a,b. Cyclocondensation of 4a,b with chloroacetone 6 and phenacyl chloride 7 gave the corresponding thiophene derivatives 9a–c. Reaction of 4a,b with C-acetyl-N- arylhydrazonoyl chlorides 14a and 14b in boiling EtOH in the presence of triethylamine, afforded the corresponding 1,3,4-thiadiazoline derivatives 16a–d. The thioamides 4a,b were reacted with C-ethoxycarbonyl-N-arylhydrazonoyl chlorides 18a,b which afforded 1,3,4-thiadiazoline derivatives 19a–d. The benzosuberones 1a,b were treated with 3-mercaptopropanoic acid to give compounds 21a,b, which were cyclized to tricyclic thiopyran-4(5H)-one derivatives 22a,b. The latter compounds 22a,b were reacted with 3-mercaptopropanoic acid to give compounds 23a,b, which were cyclized tetracyclic ring systems 24a,b. Finally, compounds 24a,b were oxidized using hydrogen peroxide under reflux conditions to afford the oxidized form of the novel tetracyclic heterogeneous ring systems 25a,b. The newly synthesized compounds were screened for antimicrobial activities. The structures of new compounds were characterized by ¹H-NMR, ¹³C-NMR, IR, and EI-MS. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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12 pages, 1414 KiB

Open AccessArticle

Optimization of Ultrasound-Assisted Extraction of Natural Antioxidants from Sugar Apple (Annona squamosa L.) Peel Using Response Surface Methodology

by Gui-Fang Deng^1,*, Dong-Ping Xu², Sha Li² and Hua-Bin Li^2,*

¹ Department of Clinical Nutrition, Nanshan Hospital, Shenzhen 518052, China

² Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China

Molecules 2015, 20(11), 20448-20459; https://doi.org/10.3390/molecules201119708 - 17 Nov 2015

Cited by 35 | Viewed by 7042

Abstract

Sugar apple (Annona squamosa L.) is a popular tropical fruit and its peel is a municipal waste. An ultrasound-assisted extraction method was developed for the recovery of natural antioxidants from sugar apple peel. Central composite design was used to optimize solvent concentration [...] Read more.

Sugar apple (Annona squamosa L.) is a popular tropical fruit and its peel is a municipal waste. An ultrasound-assisted extraction method was developed for the recovery of natural antioxidants from sugar apple peel. Central composite design was used to optimize solvent concentration (13.2%–46.8%), ultrasonic time (33.2–66.8 min), and temperature (43.2–76.8 °C) for the recovery of natural antioxidants from sugar apple peel. The second-order polynomial models demonstrated a good fit of the quadratic models with the experimental results in respect to total phenolic content (TPC, R² = 0.9524, p < 0.0001), FRAP (R² = 0.9743, p < 0.0001), and TEAC (R² = 0.9610, p < 0.0001) values. The optimal extraction conditions were 20:1 (mL/g) of solvent-to-solid ratio, 32.68% acetone, and 67.23 °C for 42.54 min under ultrasonic irradiation. Under these conditions, the maximal yield of total phenolic content was 26.81 (mg GA/g FW). The experimental results obtained under optimal conditions agreed well with the predicted results. The application of ultrasound markedly decreased extraction time and improved the extraction efficiency, compared with the conventional methods. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 1229 KiB

Open AccessArticle

Variation in Phenolics, Flavanoids, Antioxidant and Tyrosinase Inhibitory Activity of Peach Blossoms at Different Developmental Stages

by Jie-Chao Liu, Zhong-Gao Jiao^*, Wen-Bo Yang, Chun-Ling Zhang, Hui Liu and Zhen-Zhen Lv

Zhengzhou Fruit Research Institute, Chinese Academy of Agricultural Sciences, Zhengzhou 450009, China

Molecules 2015, 20(11), 20460-20472; https://doi.org/10.3390/molecules201119709 - 18 Nov 2015

Cited by 20 | Viewed by 6655

Abstract

Peach blossoms were harvested and classified into six developmental stages: (I) bud emerging stage; (II) middle bud stage; (III) large bud stage; (IV) initial-flowering stage; (V) full-flowering stage; and (VI) end-flowering stage. The contents of total phenolics, flavanoids, individual phenolic compounds as well [...] Read more.

Peach blossoms were harvested and classified into six developmental stages: (I) bud emerging stage; (II) middle bud stage; (III) large bud stage; (IV) initial-flowering stage; (V) full-flowering stage; and (VI) end-flowering stage. The contents of total phenolics, flavanoids, individual phenolic compounds as well as antioxidant and tyrosinase inhibitory activity of peach blossoms at different developmental stages were investigated. The total phenolic contents varied from 149.80 to 74.80 mg chlorogenic acid equivalents/g dry weight (DW), and the total flavanoid contents ranged from 93.03 to 44.06 mg rutin equivalents/g DW. Both the contents of total phenolics and flavanoids decreased during blossom development. Chlorogenic acid was the predominant component, accounting for 62.08%–71.09% of the total amount of identified phenolic compounds in peach blossom. The antioxidant capacities determined by different assays and tyrosinase inhibitory activity also showed descending patterns during blossom development. Significant correlations were observed between antioxidant capacities with contents of total phenolics and total flavanoids as well as chlorogenic acid, cinnamic acid and kaempferol-3-O-galactoside, while the tyrosinase inhibitory activity had lower correlations with total phenolics and total flavanoids as well as chlorogenic acid, quercetin-3-O-rhamnoside, kaempferol-3-O-galactoside and cinnamic acid. The antioxidant activities of peach blossom seemed to be more dependent on the phenolic compounds than tyrosinase inhibitory activity. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 875 KiB

Open AccessReview

Relationship between Structure and Conformational Change of the Vitamin D Receptor Ligand Binding Domain in 1α,25-Dihydroxyvitamin D3 Signaling

by Lin-Yan Wan^1,2,†, Yan-Qiong Zhang^1,†, Meng-Di Chen^1,2, You-Qin Du¹, Chang-Bai Liu^1,2,*

and Jiang-Feng Wu^1,2,*

¹ Medical College, China Three Gorges University, 8 Daxue Road, Xiling District, Yichang 443002, China

² Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, 8 Daxue Road, Xiling District, Yichang 443002, China

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 20473-20486; https://doi.org/10.3390/molecules201119713 - 18 Nov 2015

Cited by 14 | Viewed by 6046

Abstract

Vitamin D Receptor (VDR) belongs to the nuclear receptor (NR) superfamily. Whereas the structure of the ligand binding domain (LBD) of VDR has been determined in great detail, the role of its amino acid residues in stabilizing the structure and ligand triggering conformational [...] Read more.

Vitamin D Receptor (VDR) belongs to the nuclear receptor (NR) superfamily. Whereas the structure of the ligand binding domain (LBD) of VDR has been determined in great detail, the role of its amino acid residues in stabilizing the structure and ligand triggering conformational change is still under debate. There are 13 α-helices and one β-sheet in the VDR LBD and they form a three-layer sandwich structure stabilized by 10 residues. Thirty-six amino acid residues line the ligand binding pocket (LBP) and six of these residues have hydrogen-bonds linking with the ligand. In 1α,25-dihydroxyvitamin D₃ signaling, H3 and H12 play an important role in the course of conformational change resulting in the provision of interfaces for dimerization, coactivator (CoA), corepressor (CoR), and hTAF_II 28. In this paper we provide a detailed description of the amino acid residues stabilizing the structure and taking part in conformational change of VDR LBD according to functional domains. Full article

(This article belongs to the Section Bioorganic Chemistry)

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12 pages, 408 KiB

Open AccessArticle

Chemical Composition and in-Vitro Evaluation of the Antimicrobial and Antioxidant Activities of Essential Oils Extracted from Seven Eucalyptus Species

by Abdul Ghaffar^1,*, Muhammad Yameen¹, Shumaila Kiran¹, Shagufta Kamal¹, Fatima Jalal², Bushra Munir¹, Sadaf Saleem³, Naila Rafiq³, Aftab Ahmad⁴, Iram Saba⁵ and Abdul Jabbar^5,*

¹ Department of Applied Chemistry and Biochemistry, Government College University, Faisalabad 38000, Pakistan

² Department of Zoology and Fisheries, Government College University, Faisalabad 38000, Pakistan

³ Department of Chemistry, Government College for Women University, Faisalabad 38000, Pakistan

⁴ Department of Biochemistry/US-Pakistan Center for Advanced Studies in Agriculture and Food Security (USPCAS/AFS), University of Agriculture, Faisalabad 38000, Pakistan

⁵ Department of Chemistry, Government College University, Faisalabad 38000, Pakistan

Molecules 2015, 20(11), 20487-20498; https://doi.org/10.3390/molecules201119706 - 18 Nov 2015

Cited by 79 | Viewed by 10338

Abstract

Eucalyptus is well reputed for its use as medicinal plant around the globe. The present study was planned to evaluate chemical composition, antimicrobial and antioxidant activity of the essential oils (EOs) extracted from seven Eucalyptus species frequently found in South East Asia (Pakistan). [...] Read more.

Eucalyptus is well reputed for its use as medicinal plant around the globe. The present study was planned to evaluate chemical composition, antimicrobial and antioxidant activity of the essential oils (EOs) extracted from seven Eucalyptus species frequently found in South East Asia (Pakistan). EOs from Eucalyptus citriodora, Eucalyptus melanophloia, Eucalyptus crebra, Eucalyptus tereticornis, Eucalyptus globulus, Eucalyptus camaldulensis and Eucalyptus microtheca were extracted from leaves through hydrodistillation. The chemical composition of the EOs was determined through GC-MS-FID analysis. The study revealed presence of 31 compounds in E. citriodora and E. melanophloia, 27 compounds in E. crebra, 24 compounds in E. tereticornis, 10 compounds in E. globulus, 13 compounds in E. camaldulensis and 12 compounds in E. microtheca. 1,8-Cineole (56.5%), α-pinene (31.4%), citrinyl acetate (13.3%), eugenol (11.8%) and terpenene-4-ol (10.2%) were the highest principal components in these EOs. E. citriodora exhibited the highest antimicrobial activity against the five microbial species tested (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Aspergillus niger and Rhizopus solani). Gram positive bacteria were found more sensitive than Gram negative bacteria to all EOs. The diphenyl-1-picrylhydazyl (DPPH) radical scavenging activity and percentage inhibition of linoleic acid oxidation were highest in E. citriodora (82.1% and 83.8%, respectively) followed by E. camaldulensis (81.9% and 83.3%, respectively). The great variation in chemical composition of EOs from Eucalyptus, highlight its potential for medicinal and nutraceutical applications. Full article

(This article belongs to the Section Medicinal Chemistry)

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19 pages, 2048 KiB

Open AccessReview

Redox Species of Redox Flow Batteries: A Review

by Feng Pan and Qing Wang^*

Department of Materials Science and Engineering, National University of Singapore, Singapore 117575, Singapore

Molecules 2015, 20(11), 20499-20517; https://doi.org/10.3390/molecules201119711 - 18 Nov 2015

Cited by 194 | Viewed by 25494

Abstract

Due to the capricious nature of renewable energy resources, such as wind and solar, large-scale energy storage devices are increasingly required to make the best use of the renewable power. The redox flow battery is considered suitable for large-scale applications due to its [...] Read more.

Due to the capricious nature of renewable energy resources, such as wind and solar, large-scale energy storage devices are increasingly required to make the best use of the renewable power. The redox flow battery is considered suitable for large-scale applications due to its modular design, good scalability and flexible operation. The biggest challenge of the redox flow battery is the low energy density. The redox active species is the most important component in redox flow batteries, and the redox potential and solubility of redox species dictate the system energy density. This review is focused on the recent development of redox species. Different categories of redox species, including simple inorganic ions, metal complexes, metal-free organic compounds, polysulfide/sulfur and lithium storage active materials, are reviewed. The future development of redox species towards higher energy density is also suggested. Full article

(This article belongs to the Special Issue Molecular Engineering for Electrochemical Power Sources)

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20 pages, 1949 KiB

Open AccessArticle

Analysis of the Constituents in “Zhu She Yong Xue Shuan Tong” by Ultra High Performance Liquid Chromatography with Quadrupole Time-of-Flight Mass Spectrometry Combined with Preparative High Performance Liquid Chromatography

by Lin-Lin Wang^1,2, Li-Feng Han^1,2, He-Shui Yu¹, Mang-Mang Sang^1,2, Er-Wei Liu^1,2, Yi Zhang^1,2, Shi-Ming Fang^1,2, Tao Wang^1,2

and Xiu-Mei Gao^1,*

¹ Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China

² Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China

Molecules 2015, 20(11), 20518-20537; https://doi.org/10.3390/molecules201119712 - 18 Nov 2015

Cited by 24 | Viewed by 8124

Abstract

“Zhu She Yong Xue Shuan Tong” lyophilized powder (ZSYXST), consists of a series of saponins extracted from Panax notoginseng, which has been widely used in China for the treatment of strokes. In this study, an ultra-high performance liquid chromatography with quadrupole time-of-flight [...] Read more.

“Zhu She Yong Xue Shuan Tong” lyophilized powder (ZSYXST), consists of a series of saponins extracted from Panax notoginseng, which has been widely used in China for the treatment of strokes. In this study, an ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) combined with preparative high performance liquid chromatography (PHPLC) method was developed to rapidly identify both major and minor saponins in ZSYXST. Some high content components were removed through PHPLC in order to increase the sensitivity of the trace saponins. Then, specific characteristic fragment ions in both positive and negative mode were utilized to determine the types of aglycone, saccharide, as well as the saccharide chain linkages. As a result, 94 saponins, including 20 pairs of isomers and ten new compounds, which could represent higher than 98% components in ZSYXST, were identified or tentatively identified in commercial ZSYXST samples. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 5842 KiB

Open AccessArticle

Agrimonia eupatoria L. and Cynara cardunculus L. Water Infusions: Phenolic Profile and Comparison of Antioxidant Activities

by Anika Kuczmannová^1,†, Peter Gál^{1,2,3,4,*,†}, Lenka Varinská^2,3

, Jakub Treml⁵, Ivan Kováč^3,6, Martin Novotný^3,7, Tomáš Vasilenko^3,8, Stefano Dall’Acqua⁹

, Milan Nagy¹ and Pavel Mučaji^1,*

¹ Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University, Odbojárov 10, 832 32 Bratislava, Slovakia

² Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, Trieda SNP 1, 040 11 Košice, Slovakia

³ Department for Biomedical Research, East-Slovak Institute of Cardiovascular Diseases, Inc., Ondavská 8, 040 11 Košice, Slovakia

⁴ Institute of Anatomy, 1st Faculty of Medicine, Charles University, U nemocnice 2, 128 00 Prague, Czech Republic

⁵ Department of Molecular Biology and Pharmaceutical Biotechnology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackého 1-3, 612 42 Brno, Czech Republic

⁶ 2nd Department of Surgery, Pavol Jozef Šafárik University and Louise Pasteur University Hospital, 041 90 Košice, Slovakia

⁷ Department of Infectology and Travel Medicine, Pavol Jozef Šafárik University and Louise Pasteur University Hospital, 041 90 Košice, Slovakia

⁸ Department of Surgery, Pavol Jozef Šafárik University and Košice-Šaca Hospital, 040 15 Košice-Šaca, Slovakia

⁹ Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via F. Marzolo 5, 351 31 Padova, Italy

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 20538-20550; https://doi.org/10.3390/molecules201119715 - 18 Nov 2015

Cited by 32 | Viewed by 7792

Abstract

Reactive oxygen species (ROS) are highly considered in the ethiopathogenesis of different pathological conditions because they may cause significant damage to cells and tissues. In this paper, we focused on potential antioxidant properties of two medical plants such as the Agrimonia eupatoria L. [...] Read more.

Reactive oxygen species (ROS) are highly considered in the ethiopathogenesis of different pathological conditions because they may cause significant damage to cells and tissues. In this paper, we focused on potential antioxidant properties of two medical plants such as the Agrimonia eupatoria L. and Cynara cardunculus L. Both plants have previously been studied for their pharmacological activities, especially as hepatoprotective and hypoglycemic activities. It has been suggested, that their effects are related to the antioxidant properties of polyphenols, which are dominant compounds of the plants’ extracts. In the present study HPLC-MS analysis of water infusion was performed allowing the identification of several phenolic constituents. Furthermore, antioxidant effects of the two extracts were compared showing higher effects for agrimony extract compared to artichoke. Thus, agrimony was selected for the in vivo study using the skin flap viability model. In conclusion, our results provide evidence that the A. eupatoria extract may be a valuable source of polyphenols to be studied for the future development of supplements useful in the prevention of diseases linked to oxidative stress. Full article

(This article belongs to the Section Natural Products Chemistry)

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18 pages, 3316 KiB

Open AccessReview

Recent Advances in Developing Inhibitors for Hypoxia-Inducible Factor Prolyl Hydroxylases and Their Therapeutic Implications

by So Yeon Kim^1,2 and Eun Gyeong Yang^1,3,*

¹ Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Korea

² Department of Biomedical Engineering, Korea University of Science and Technology (UST), KIST campus, Seoul 136-791, Korea

³ Department of Biological Chemistry, Korea University of Science and Technology (UST), KIST campus, Seoul 136-791, Korea

Molecules 2015, 20(11), 20551-20568; https://doi.org/10.3390/molecules201119717 - 19 Nov 2015

Cited by 64 | Viewed by 15179

Abstract

Hypoxia-inducible factor (HIF) prolyl hydroxylases (PHDs) are members of the 2-oxoglutarate dependent non-heme iron dioxygenases. Due to their physiological roles in regulation of HIF-1α stability, many efforts have been focused on searching for selective PHD inhibitors to control HIF-1α levels for therapeutic applications. [...] Read more.

Hypoxia-inducible factor (HIF) prolyl hydroxylases (PHDs) are members of the 2-oxoglutarate dependent non-heme iron dioxygenases. Due to their physiological roles in regulation of HIF-1α stability, many efforts have been focused on searching for selective PHD inhibitors to control HIF-1α levels for therapeutic applications. In this review, we first describe the structure of PHD2 as a molecular basis for structure-based drug design (SBDD) and various experimental methods developed for measuring PHD activity. We further discuss the current status of the development of PHD inhibitors enabled by combining SBDD approaches with high-throughput screening. Finally, we highlight the clinical implications of small molecule PHD inhibitors. Full article

(This article belongs to the Special Issue Chemoinformatics)

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13 pages, 6320 KiB

Open AccessArticle

Ardipusilloside-I Metabolites from Human Intestinal Bacteria and Their Antitumor Activity

by Wei-Yu Cao¹, Ya-Nan Wang², Peng-Yuan Wang¹, Wan Lei¹, Bin Feng¹ and Xiao-Juan Wang^1,*

¹ State Key Laboratory of Military Stomatology, Department of Pharmacy, School of Stomatology, The Fourth Military Medical University, Xi’an 710032, China

² State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

Molecules 2015, 20(11), 20569-20581; https://doi.org/10.3390/molecules201119719 - 19 Nov 2015

Cited by 12 | Viewed by 6041

Abstract

Ardipusilloside-I (ADS-I) is a triterpenoid saponin extracted from Ardisia pusilla DC, and has been demonstrated to have potent antitumor activity. However, ADS-I metabolism in humans has not been investigated. In this study, we studied the biotransformation of ADS-I in human intestinal bacteria, and [...] Read more.

Ardipusilloside-I (ADS-I) is a triterpenoid saponin extracted from Ardisia pusilla DC, and has been demonstrated to have potent antitumor activity. However, ADS-I metabolism in humans has not been investigated. In this study, we studied the biotransformation of ADS-I in human intestinal bacteria, and examined the in vitro antitumor activity of the major metabolites. Ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) was used to detect ADS-I biotransformation products, and their chemical structures were identified by high performance liquid chromatography–nuclear magnetic resonance (HPLC–NMR). The antitumor activity of the major metabolites was determined by the MTT assay. Here, we show that main reaction seen in the metabolism of ADS-I in human intestinal bacteria was deglycosylation, which produced a total of four metabolites. The structures of the two major metabolites M1 and M2 were confirmed by using NMR. MTT assay showed that ADS-I metabolites M1 and M2 have the same levels of inhibitory activities as ADS-I in cultured SMMC-7721 cells and MCF-7 cells. In conclusion, this study demonstrates deglycosylation as a primary pathway of ADS-I metabolism in human intestinal bacteria, and suggests that the pharmacological activity of ADS-I may be mediated, at least in part, by its metabolites. Full article

(This article belongs to the Special Issue New Technologies for the Recovery of Natural Products)

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32 pages, 6098 KiB

Open AccessReview

Immobilization of Metal Hexacyanoferrate Ion-Exchangers for the Synthesis of Metal Ion Sorbents—A Mini-Review

by Thierry Vincent, Chloë Vincent and Eric Guibal^*

¹ Ecole des mines d’Alès, Centre des Matériaux des Mines d’Alès, 6, avenue de Clavières, F-30319 ALES cedex, France

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 20582-20613; https://doi.org/10.3390/molecules201119718 - 19 Nov 2015

Cited by 118 | Viewed by 13435

Abstract

Metal hexacyanoferrates are very efficient sorbents for the recovery of alkali and base metal ions (including radionuclides such as Cs). Generally produced by the direct reaction of metal salts with potassium hexacyanoferrate (the precursors), they are characterized by ion-exchange and structural properties that [...] Read more.

Metal hexacyanoferrates are very efficient sorbents for the recovery of alkali and base metal ions (including radionuclides such as Cs). Generally produced by the direct reaction of metal salts with potassium hexacyanoferrate (the precursors), they are characterized by ion-exchange and structural properties that make then particularly selective for Cs(I), Rb(I) and Tl(I) recovery (based on their hydrated ionic radius consistent with the size of the ion-exchanger cage), though they can bind also base metals. The major drawback of these materials is associated to their nanometer or micrometer size that makes them difficult to recover in large-size continuous systems. For this reason many techniques have been designed for immobilizing these ion-exchangers in suitable matrices that can be organic (mainly polymers and biopolymers) or inorganic (mineral supports), carbon-based matrices. This immobilization may proceed by in situ synthesis or by entrapment/encapsulation. This mini-review reports some examples of hybrid materials synthesized for the immobilization of metal hexacyanoferrate, the different conditionings of these composite materials and, briefly, the parameters to take into account for their optimal design and facilitated use. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Organic Chemistry)

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28 pages, 1177 KiB

Open AccessReview

Ursolic Acid—A Pentacyclic Triterpenoid with a Wide Spectrum of Pharmacological Activities

by Łukasz Woźniak^*

, Sylwia Skąpska and Krystian Marszałek

Department of Fruit and Vegetable Product Technology, Institute of Agricultural and Food Biotechnology, 36 Rakowiecka Street, 02-532 Warsaw, Poland

Molecules 2015, 20(11), 20614-20641; https://doi.org/10.3390/molecules201119721 - 19 Nov 2015

Cited by 330 | Viewed by 24640

Abstract

Ursolic acid (UA) is a natural terpene compound exhibiting many pharmaceutical properties. In this review the current state of knowledge about the health-promoting properties of this widespread, biologically active compound, as well as information about its occurrence and biosynthesis are presented. Particular attention [...] Read more.

Ursolic acid (UA) is a natural terpene compound exhibiting many pharmaceutical properties. In this review the current state of knowledge about the health-promoting properties of this widespread, biologically active compound, as well as information about its occurrence and biosynthesis are presented. Particular attention has been paid to the application of ursolic acid as an anti-cancer agent; it is worth noticing that clinical tests suggesting the possibility of practical use of UA have already been conducted. Amongst other pharmacological properties of UA one can mention protective effect on lungs, kidneys, liver and brain, anti-inflammatory properties, anabolic effects on skeletal muscles and the ability to suppress bone density loss leading to osteoporosis. Ursolic acid also exhibits anti-microbial features against numerous strains of bacteria, HIV and HCV viruses and Plasmodium protozoa causing malaria. Full article

(This article belongs to the Special Issue Dietary Bioactive Compounds: Metabolism, Mechanisms and Translational Significance for Health and Prevention of Diseases)

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17 pages, 3151 KiB

Open AccessArticle

New Diethyl Ammonium Salt of Thiobarbituric Acid Derivative: Synthesis, Molecular Structure Investigations and Docking Studies

by Assem Barakat^1,3,*,†

, Abdullah Mohammed Al-Majid^1,†, Saied M. Soliman^2,3,†

, Gehad Lotfy^4,†, Hazem A. Ghabbour^5,†

, Hoong-Kun Fun^5,6,†, Abdul Wadood^7,†, Ismail Warad^8,† and Joseph C. Sloop^9,†

¹ Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia

² Department of Chemistry, College of Science & Arts, King Abdulaziz University, P. O. Box 344,Rabigh 21911, Saudi Arabia

³ Department of Chemistry, Faculty of Science, Alexandria University, P. O. Box 426, Ibrahimia, Alexandria 21321, Egypt

⁴ Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt

⁵ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi Arabia

⁶ X-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, Penang 11800, Malaysia

⁷ Department of Biochemistry, Abdul Wali Khan University, Mardan-23200, Pakistan

⁸ Department of Chemistry, Science College, Al-Najah National University, P. O. Box 7, Nablus 0097, Palestine

⁹ School of Science and Technology, Georgia Gwinnett College, 1000 University Center Lane, Lawrenceville, GA 30043, USA

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 20642-20658; https://doi.org/10.3390/molecules201119710 - 19 Nov 2015

Cited by 14 | Viewed by 7196

Abstract

The synthesis of the new diethyl ammonium salt of diethylammonium(E)-5-(1,5-bis(4-fluorophenyl)-3-oxopent-4-en-1-yl)-1,3-diethyl-4,6-dioxo-2-thioxohexaydropyrimidin-5-ide 3 via a regioselective Michael addition of N,N-diethylthiobarbituric acid 1 to dienone 2 is described. In 3, the carboanion of the thiobarbituric moiety is stabilized [...] Read more.

The synthesis of the new diethyl ammonium salt of diethylammonium(E)-5-(1,5-bis(4-fluorophenyl)-3-oxopent-4-en-1-yl)-1,3-diethyl-4,6-dioxo-2-thioxohexaydropyrimidin-5-ide 3 via a regioselective Michael addition of N,N-diethylthiobarbituric acid 1 to dienone 2 is described. In 3, the carboanion of the thiobarbituric moiety is stabilized by the strong intramolecular electron delocalization with the adjacent carbonyl groups and so the reaction proceeds without any cyclization. The molecular structure investigations of 3 were determined by single-crystal X-ray diffraction as well as DFT computations. The theoretically calculated (DFT/B3LYP) geometry agrees well with the crystallographic data. The effect of fluorine replacement by chlorine atoms on the molecular structure aspects were investigated using DFT methods. Calculated electronic spectra showed a bathochromic shift of the π-π* transition when fluorine is replaced by chlorine. Charge decomposition analyses were performed to study possible interaction between the different fragments in the studied systems. Molecular docking simulations examining the inhibitory nature of the compound show an anti-diabetic activity with Pa (probability of activity) value of 0.229. Full article

(This article belongs to the Section Medicinal Chemistry)

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10 pages, 3166 KiB

Open AccessArticle

Cyclovirobuxine D Inhibits Cell Proliferation and Induces Mitochondria-Mediated Apoptosis in Human Gastric Cancer Cells

by Jie Wu^1,2,*

, Zhujun Tan³, Jian Chen⁴ and Cheng Dong^1,5

¹ School of Naval Architecture, Ocean and Civil Engineering, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Shanghai 200240, China

² Ministry of Education of China (MOE) Key Laboratory of Hydrodynamics, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Shanghai 200240, China

³ Department of General Surgery, School of Medicine, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, Shanghai 200092, China

⁴ School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Shanghai 200240, China

⁵ Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA 16802, USA

Molecules 2015, 20(11), 20659-20668; https://doi.org/10.3390/molecules201119729 - 19 Nov 2015

Cited by 22 | Viewed by 6188

Abstract

Gastric cancer is one of the most common malignant cancers, with high death rates, poor prognosis and limited treatment methods. Cyclovirobuxine D (CVB-D) is the main active component of the traditional Chinese medicine Buxus microphylla. In the present study, we test the effects [...] Read more.

Gastric cancer is one of the most common malignant cancers, with high death rates, poor prognosis and limited treatment methods. Cyclovirobuxine D (CVB-D) is the main active component of the traditional Chinese medicine Buxus microphylla. In the present study, we test the effects of CVB-D on gastric cancer cells and the underlying mechanisms of action. CVB-D reduced cell viability and colony formation ability of MGC-803 and MKN28 cells in a time- and concentration-dependent manner. Flow cytometry showed that cell cycle of CVB-D treated cells was arrested at the S-phase. CVB-D also induced apoptosis in MGC-803 and MKN28 cells, especially early stage apoptosis. Furthermore, mitochondria membrane potential (Δψm) was reduced and apoptosis-related proteins, cleaved Caspase-3 and Bax/Bcl-2, were up-regulated in CVB-D-treated MGC-803 and MKN28 cells. Taken together, our studies found that CVB-D plays important roles in inhibition of gastric tumorigenesis via arresting cell cycle and inducing mitochondria-mediated apoptosis, suggesting the potential application of CVB-D in gastric cancer therapy. Full article

(This article belongs to the Section Medicinal Chemistry)

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19 pages, 1164 KiB

Open AccessReview

The Effect of Low Monotonic Doses of Zearalenone on Selected Reproductive Tissues in Pre-Pubertal Female Dogs—A Review

by Magdalena Gajęcka^1,*, Łukasz Zielonka² and Maciej Gajęcki²

¹ Department of Epizootiology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 13/01, Olsztyn 10-718, Poland

² Department of Veterinary Prevention and Feed Hygiene, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 13/29, Olsztyn 10-718, Poland

Molecules 2015, 20(11), 20669-20687; https://doi.org/10.3390/molecules201119726 - 19 Nov 2015

Cited by 27 | Viewed by 7480

Abstract

The growing interest in toxic substances combined with advancements in biological sciences has shed a new light on the problem of mycotoxins contaminating feeds and foods. An interdisciplinary approach was developed by identifying dose-response relationships in key research concepts, including the low dose [...] Read more.

The growing interest in toxic substances combined with advancements in biological sciences has shed a new light on the problem of mycotoxins contaminating feeds and foods. An interdisciplinary approach was developed by identifying dose-response relationships in key research concepts, including the low dose theory of estrogen-like compounds, hormesis, NOAEL dose, compensatory response and/or food tolerance, and effects of exposure to undesirable substances. The above considerations increased the researchers’ interest in risk evaluation, namely: (i) clinical symptoms associated with long-term, daily exposure to low doses of a toxic compound; and (ii) dysfunctions at cellular or tissue level that do not produce clinical symptoms. Research advancements facilitate the extrapolation of results and promote the use of novel tools for evaluating the risk of exposure, for example exposure to zearalenone in pre-pubertal female dogs. The arguments presented in this paper suggest that low doses of zearalenone in commercial feeds stimulate metabolic processes and increase weight gains. Those processes are accompanied by lower proliferation rates in the ovaries, neoangiogenesis and vasodilation in the ovaries and the uterus, changes in the steroid hormone profile, and changes in the activity of hydroxysteroid dehydrogenases. All of the above changes result from exogenous hyperestrogenizm. Full article

(This article belongs to the Special Issue Natural Toxins)

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11 pages, 2782 KiB

Open AccessArticle

Solvatochromic and Single Crystal Studies of Two Neutral Triarylmethane Dyes with a Quinone Methide Structure

by Katherine Chulvi, Ana M. Costero^*

, Luis E. Ochando, Salvador Gil

, José-Luis Vivancos

and Pablo Gaviña^*

Centro de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat de València-Universidad Politécnica de Valencia, Dr. Moliner, 50, 46100-Burjassot, Valencia, Spain

Molecules 2015, 20(11), 20688-20698; https://doi.org/10.3390/molecules201119724 - 19 Nov 2015

Cited by 4 | Viewed by 7354

Abstract

The crystal structure of two neutral triarylmethane dyes with a p-quinone methide core was determined by X-ray diffraction analysis. The spectroscopic characteristics of both compounds in 23 solvents with different polarities or hydrogen-bonding donor (HBD) abilities has been studied as a function of [...] Read more.

The crystal structure of two neutral triarylmethane dyes with a p-quinone methide core was determined by X-ray diffraction analysis. The spectroscopic characteristics of both compounds in 23 solvents with different polarities or hydrogen-bonding donor (HBD) abilities has been studied as a function of three solvatochromic parameters (E_T(30), π* and α). Both compounds 1 and 2 showed a pronounced bathochromic shift of the main absorption band on increasing solvent polarity and HBD ability. The correlation is better for compound 2 than for compound 1. The stronger effect and better correlation was observed for compound 2 with the increment of the solvent HBD ability (α parameter). Full article

(This article belongs to the Special Issue Photoactive Molecules)

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10 pages, 1883 KiB

Open AccessArticle

Cinidium officinale and its Bioactive Compound, Butylidenephthalide, Inhibit Laser-Induced Choroidal Neovascularization in a Rat Model

by Yun Mi Lee^1,2, Yu Ri Lee², Jin Sook Kim², Young Ho Kim^1,† and Junghyun Kim^2,*,†

¹ College of Pharmacy, Chungnam National University, Daejeon 34134, Korea

² Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea

^† These authors are co-corresponding authors.

Molecules 2015, 20(11), 20699-20708; https://doi.org/10.3390/molecules201119728 - 19 Nov 2015

Cited by 8 | Viewed by 6376

Abstract

Choroidal neovascularization (CNV) is a common pathology in age-related macular degeneration. In this study, we evaluated in a rat model the effect of an extract of Cinidium officinale Makino and its bioactive compound, butylidenephthalide, on laser-induced CNV. Experimental CNV was induced in Long-Evans [...] Read more.

Choroidal neovascularization (CNV) is a common pathology in age-related macular degeneration. In this study, we evaluated in a rat model the effect of an extract of Cinidium officinale Makino and its bioactive compound, butylidenephthalide, on laser-induced CNV. Experimental CNV was induced in Long-Evans rats by laser photocoagulation. C. officinale extract (COE) and butylidenephthalide was intraperitoneally injected once per day for ten days after laser photocoagulation. Choroidal flat mounts were prepared to measure CNV areas and macrophage infiltration. We used a protein array to evaluate the expression levels of angiogenic factors. The CNV area and macrophage infiltration in COE-treated rats were significantly lower than in vehicle-treated rats. COE decreased the expression levels of IGFBP-1, MCP-1, PAI-1, and VEGF. Additionally, butylidenephthalide also inhibited the laser-induced CNV formation and macrophage infiltration and down-regulated the expression of IGFBP-1, MCP-1 and VEGF. These results suggest that COE exerts anti-angiogenic effects on laser-induced CNV by inhibiting the expression of IGFBP-1, MCP-1, and VEGF, indicating that anti-angiogenic activities of COE may be in part due to its bioactive compound, butylidenephthalide. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 5212 KiB

Open AccessCommunication

An Efficient and Recyclable Nanoparticle-Supported Cobalt Catalyst for Quinoxaline Synthesis

by Fatemeh Rajabi^1,*, Diego Alves²

and Rafael Luque³

¹ Department of Science, Payame Noor University, P. O. Box: 19395-4697, Tehran 19569, Iran

² Laboratório de Síntese Orgânica Limpa—LASOL, Universidade Federal de Pelotas UFPEL, Pelotas, CEP 96010-900, Brazil

³ Departamento de Quimica Organica, Universidad de Cordoba, Campus de Rabanales, Edificio Marie Curie (C3), Ctra Nnal IV-A, Km 396, Cordoba E14014, Spain

Molecules 2015, 20(11), 20709-20718; https://doi.org/10.3390/molecules201119731 - 19 Nov 2015

Cited by 17 | Viewed by 6914

Abstract

The syntheses of quinoxalines derived from 1,2-diamine and 1,2-dicarbonyl compounds under mild reaction conditions was carried out using a nanoparticle-supported cobalt catalyst. The supported nanocatalyst exhibited excellent activity and stability and it could be reused for at least ten times without any loss [...] Read more.

The syntheses of quinoxalines derived from 1,2-diamine and 1,2-dicarbonyl compounds under mild reaction conditions was carried out using a nanoparticle-supported cobalt catalyst. The supported nanocatalyst exhibited excellent activity and stability and it could be reused for at least ten times without any loss of activity. No cobalt contamination could be detected in the products by AAS measurements, pointing to the excellent activity and stability of the Co nanomaterial. Full article

(This article belongs to the Special Issue Metal Nanocatalysts in Green Synthesis and Energy Applications)

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22 pages, 2052 KiB

Open AccessArticle

Condensation of Diacetyl with Alkyl Amines: Synthesis and Reactivity of p-Iminobenzoquinones and p-Diiminobenzoquinones

by Carlos Espinoza-Hicks, Rafael Bautista^†, Saúl Frias-Puente, Vanessa Pelayo, Eder I. Martínez-Mora, Francisco Delgado and Joaquín Tamariz^*

¹ Departamento de Química Orgánica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional. Prol. Carpio y Plan de Ayala, 11340 México, Mexico

^† Present address: Departamento de Investigación y Desarrollo, Signa, S.A. de C.V., Av. Industria Automotriz No. 301, Zona Industrial Toluca, 50200, Toluca, Edo. de México, Mexico.

Molecules 2015, 20(11), 20719-20740; https://doi.org/10.3390/molecules201119716 - 20 Nov 2015

Cited by 3 | Viewed by 9290

Abstract

Condensation reactions between diacetyl and α-branched primary alkylamines under mild and neutral conditions provided a mixture of 2,5-dimethylbenzoquinone(alkylimines), 2,5-dimethylbenzoquinone(bis-alkyldiimines), and N,N′-dialkyl-2,5-dimethylbenzene-1,4-diamines, which were efficiently separated as pure products by column chromatography. Both 2,5-dimethylbenzoquinone(alkylimines) and 2,5-dimethylbenzoquinone(bis-alkyldiimines) underwent [...] Read more.

Condensation reactions between diacetyl and α-branched primary alkylamines under mild and neutral conditions provided a mixture of 2,5-dimethylbenzoquinone(alkylimines), 2,5-dimethylbenzoquinone(bis-alkyldiimines), and N,N′-dialkyl-2,5-dimethylbenzene-1,4-diamines, which were efficiently separated as pure products by column chromatography. Both 2,5-dimethylbenzoquinone(alkylimines) and 2,5-dimethylbenzoquinone(bis-alkyldiimines) underwent an interchange of the alkylimino group when treated with anilines, followed by reductive aromatization, to provide diarylamines and 1,4-dianilinobenzenes, respectively. Evaluation was also made of the reactivity and selectivity of these compounds in the presence of anilines, thiophenols and alkylhalides. Full article

(This article belongs to the Section Organic Chemistry)

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36 pages, 10832 KiB

Open AccessReview

Current Research on Antiepileptic Compounds

by Cheng-Xi Wei^1,†, Ming Bian^1,† and Guo-Hua Gong^1,2,*

¹ Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for the Nationalities, Tongliao 028000, China

² Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao 028000, Inner Mongolia, China

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 20741-20776; https://doi.org/10.3390/molecules201119714 - 20 Nov 2015

Cited by 27 | Viewed by 9636

Abstract

Epilepsy affects about 1% of the world’s population. Due to the fact all antiepileptic drugs (AEDs) have some undesirable side effects and about 30% of epileptic patients are not seizure-free with the existing AEDs, there is still an urgent need for the development [...] Read more.

Epilepsy affects about 1% of the world’s population. Due to the fact all antiepileptic drugs (AEDs) have some undesirable side effects and about 30% of epileptic patients are not seizure-free with the existing AEDs, there is still an urgent need for the development of more effective and safer AEDs. Based on our research work on antiepileptic compounds and other references in recent years, this review covers the reported work on antiepileptic compounds which are classified according to their structures. This review summarized 244 significant anticonvulsant compounds which are classified by functional groups according to the animal model data, although there are some limitations in the data. This review highlights the properties of new compounds endowed with promising antiepileptic properties, which may be proven to be more effective and selective, and possibly free of unwanted side effects. The reviewed compounds represent an interesting possibility to overcome refractory seizures and to reduce the percentage of patients with a poor response to drug therapy. Full article

(This article belongs to the Section Medicinal Chemistry)

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28 pages, 5193 KiB

Open AccessReview

DNA Catalysis: The Chemical Repertoire of DNAzymes

by Marcel Hollenstein^†

¹ Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern, Switzerland

^† Present address: Institut Pasteur, Chemistry and Structural Biology Department, Laboratory for Bioorganic Chemistry of Nucleic Acids, 28 rue du Dr Roux, 75724 Paris cedex 15, France.

Molecules 2015, 20(11), 20777-20804; https://doi.org/10.3390/molecules201119730 - 20 Nov 2015

Cited by 143 | Viewed by 18780

Abstract

Deoxyribozymes or DNAzymes are single-stranded catalytic DNA molecules that are obtained by combinatorial in vitro selection methods. Initially conceived to function as gene silencing agents, the scope of DNAzymes has rapidly expanded into diverse fields, including biosensing, diagnostics, logic gate operations, and the [...] Read more.

Deoxyribozymes or DNAzymes are single-stranded catalytic DNA molecules that are obtained by combinatorial in vitro selection methods. Initially conceived to function as gene silencing agents, the scope of DNAzymes has rapidly expanded into diverse fields, including biosensing, diagnostics, logic gate operations, and the development of novel synthetic and biological tools. In this review, an overview of all the different chemical reactions catalyzed by DNAzymes is given with an emphasis on RNA cleavage and the use of non-nucleosidic substrates. The use of modified nucleoside triphosphates (dN*TPs) to expand the chemical space to be explored in selection experiments and ultimately to generate DNAzymes with an expanded chemical repertoire is also highlighted. Full article

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

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18 pages, 3630 KiB

Open AccessArticle

A 7-Deazaadenosylaziridine Cofactor for Sequence-Specific Labeling of DNA by the DNA Cytosine-C5 Methyltransferase M.HhaI

by Falk Kunkel^1,†, Rudi Lurz² and Elmar Weinhold^1,*

¹ Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, Aachen D-52056, Germany

² Max-Planck-Institute for Molecular Genetics, Ihnestrasse 73, Berlin D-14195, Germany

^† Present address: Eckert & Ziegler Eurotope GmbH, Robert-Rössle-Str. 10, Berlin D-13125, Germany.

Molecules 2015, 20(11), 20805-20822; https://doi.org/10.3390/molecules201119723 - 23 Nov 2015

Cited by 13 | Viewed by 7489

Abstract

DNA methyltransferases (MTases) catalyze the transfer of the activated methyl group of the cofactor S-adenosyl-l-methionine (AdoMet or SAM) to the exocyclic amino groups of adenine or cytosine or the C5 ring atom of cytosine within specific DNA sequences. The DNA adenine-N6 MTase [...] Read more.

DNA methyltransferases (MTases) catalyze the transfer of the activated methyl group of the cofactor S-adenosyl-l-methionine (AdoMet or SAM) to the exocyclic amino groups of adenine or cytosine or the C5 ring atom of cytosine within specific DNA sequences. The DNA adenine-N6 MTase from Thermus aquaticus (M.TaqI) is also capable of coupling synthetic N-adenosylaziridine cofactor analogues to its target adenine within the double-stranded 5′-TCGA-3′ sequence. This M.TaqI-mediated coupling reaction was exploited to sequence-specifically deliver fluorophores and biotin to DNA using N-adenosylaziridine derivatives carrying reporter groups at the 8-position of the adenine ring. However, these 8-modified aziridine cofactors were poor substrates for the DNA cytosine-C5 MTase from Haemophilus haemolyticus (M.HhaI). Based on the crystal structure of M.HhaI in complex with a duplex oligodeoxynucleotide and the cofactor product, we synthesized a stable 7-deazaadenosylaziridine derivative with a biotin group attached to the 7-position via a flexible linker. This 7-modified aziridine cofactor can be efficiently used by M.HhaI for the direct, quantitative and sequence-specific delivery of biotin to the second cytosine within 5′-GCGC-3′ sequences in short duplex oligodeoxynucleotides and plasmid DNA. In addition, we demonstrate that biotinylation by M.HhaI depends on the methylation status of the target cytosine and, thus, could provide a method for cytosine-C5 DNA methylation detection in mammalian DNA. Full article

(This article belongs to the Special Issue Frontiers in Nucleic Acid Chemistry)

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9 pages, 567 KiB

Open AccessCommunication

Two New Cyototoxic Cardenolides from the Whole Plants of Adonis multiflora Nishikawa & Koki Ito

by Jae-Woo Jung¹, Nam-In Baek¹

, Jeon Hwang-Bo², Seung-Su Lee¹

, Ji-Hae Park¹, Kyeong-Hwa Seo¹, Jung-Hwa Kwon¹, Eun-Ji Oh¹, Dae-Young Lee³

, In-Sik Chung² and Myun-Ho Bang^1,*

¹ Graduate School of Biotechnology and Department of Oriental Medicine Biotechnology, Kyung Hee University, Yongin 446-701, Korea

² Graduate School of Biotechnology and Department of Genetic Engineering, Kyung Hee University, Yongin 446-701, Korea

³ Department of Herbal Crop Research, National Institute of Horicultural and Herbal Science, RDA, Eumseong 369-873, Korea

Molecules 2015, 20(11), 20823-20831; https://doi.org/10.3390/molecules201119722 - 23 Nov 2015

Cited by 8 | Viewed by 5788

Abstract

A phytochemical investigation of the whole plants of Adonis multiflora Nishikawa & Koki Ito. resulted in the isolation and identification of two new cardenolides—adonioside A (1) and adonioside B (6)—as well as four known cardenolides: tupichinolide (2) [...] Read more.

A phytochemical investigation of the whole plants of Adonis multiflora Nishikawa & Koki Ito. resulted in the isolation and identification of two new cardenolides—adonioside A (1) and adonioside B (6)—as well as four known cardenolides: tupichinolide (2) oleandrine (3), cryptostigmin II (4), and cymarin (5). Their structures were elucidated on the basis of NMR, MS, and IR spectroscopic analyses. Compounds 1, 2, 5, and 6 showed significant cytotoxicity against six human cancer cell lines (HCT-116, HepG2, HeLa, SK-OV-3, and SK-MEL-5, and SK-BR-3). Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 2165 KiB

Open AccessArticle

Identification of RNA Oligonucleotides Binding to Several Proteins from Potential G-Quadruplex Forming Regions in Transcribed Pre-mRNA

by Taiki Saito^1,†, Wataru Yoshida^2,†, Tomomi Yokoyama¹, Koichi Abe¹ and Kazunori Ikebukuro^1,*

¹ Department of Biotechnology and Life Science, Graduate School of Engineering, Tokyo University of Agriculture & Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan

² School of Biotechnology and Bioscience Tokyo University of Technology, 1404-1 Katakura-cho, Hachioji, Tokyo 192-0982, Japan

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 20832-20840; https://doi.org/10.3390/molecules201119733 - 23 Nov 2015

Cited by 7 | Viewed by 7096

Abstract

G-quadruplexes (G4s) are noncanonical DNA/RNA structures formed by guanine-rich sequences. Recently, G4s have been found not only in aptamers but also in the genomic DNA and transcribed RNA. In this study, we identified new RNA oligonucleotides working as aptamers by focusing on G4-forming [...] Read more.

G-quadruplexes (G4s) are noncanonical DNA/RNA structures formed by guanine-rich sequences. Recently, G4s have been found not only in aptamers but also in the genomic DNA and transcribed RNA. In this study, we identified new RNA oligonucleotides working as aptamers by focusing on G4-forming RNAs located within the pre-mRNA. We showed that the G4 in the 5′ UTR and first intron of VEGFA bound to the protein encoded in VEGFA gene, VEGF165, with high affinity. Moreover, G4-forming RNAs located within the PDGFA and the PDGFB introns bound to PDGF-AA and PDGF-BB, respectively, indicating that G4 in the pre-mRNA could be an aptamer. It had been reported that the putative G4-forming RNA sequences are located in some parts of most genes, thus our strategy for aptamer identification could be applicable to other proteins. It has been reported that some G4-forming RNAs in 5′ UTRs are involved in translation control; however, G4-forming excised intronic RNA function has not been revealed previously. Therefore, these findings could not only contribute to the identification of RNA aptamers but also provide new insights into the biological functioning of G4-forming RNAs located within intronic RNA sequences. Full article

(This article belongs to the Special Issue Aptamers: Past, Present, and Future)

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32 pages, 1913 KiB

Open AccessReview

Phytochelators Intended for Clinical Use in Iron Overload, Other Diseases of Iron Imbalance and Free Radical Pathology

by Christina N. Kontoghiorghe, Annita Kolnagou and George J. Kontoghiorghes^*

Postgraduate Research Institute of Science, Technology, Environment and Medicine, 3 Ammochostou Street, Limassol 3021, Cyprus

Molecules 2015, 20(11), 20841-20872; https://doi.org/10.3390/molecules201119725 - 23 Nov 2015

Cited by 57 | Viewed by 10442

Abstract

Iron chelating drugs are primarily and widely used in the treatment of transfusional iron overload in thalassaemia and similar conditions. Recent in vivo and clinical studies have also shown that chelators, and in particular deferiprone, can be used effectively in many conditions involving [...] Read more.

Iron chelating drugs are primarily and widely used in the treatment of transfusional iron overload in thalassaemia and similar conditions. Recent in vivo and clinical studies have also shown that chelators, and in particular deferiprone, can be used effectively in many conditions involving free radical damage and pathology including neurodegenerative, renal, hepatic, cardiac conditions and cancer. Many classes of phytochelators (Greek: phyto (φυτό)—plant, chele (χηλή)—claw of the crab) with differing chelating properties, including plant polyphenols resembling chelating drugs, can be developed for clinical use. The phytochelators mimosine and tropolone have been identified to be orally active and effective in animal models for the treatment of iron overload and maltol for the treatment of iron deficiency anaemia. Many critical parameters are required for the development of phytochelators for clinical use including the characterization of the therapeutic targets, ADMET, identification of the therapeutic index and risk/benefit assessment by comparison to existing therapies. Phytochelators can be developed and used as main, alternative or adjuvant therapies including combination therapies with synthetic chelators for synergistic and or complimentary therapeutic effects. The development of phytochelators is a challenging area for the introduction of new pharmaceuticals which can be used in many diseases and also in ageing. The commercial and other considerations for such development have great advantages in comparison to synthetic drugs and could also benefit millions of patients in developing countries. Full article

(This article belongs to the Section Metabolites)

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14 pages, 3877 KiB

Open AccessArticle

Synthesis of Tertiary and Quaternary Amine Derivatives from Wood Resin as Chiral NMR Solvating Agents

by Tiina Laaksonen, Sami Heikkinen and Kristiina Wähälä^*

Department of Chemistry, University of Helsinki, A.I. Virtasen aukio 1, P. O. Box 55, FI-00014, Helsinki 00100, Finland

Molecules 2015, 20(11), 20873-20886; https://doi.org/10.3390/molecules201119732 - 23 Nov 2015

Cited by 12 | Viewed by 8671

Abstract

Chiral tertiary and quaternary amine solvating agents for NMR spectroscopy were synthesized from the wood resin derivative (+)-dehydroabietylamine (2). The resolution of enantiomers of model compounds [Mosher’s acid (3) and its n-Bu₄N salt (4)] [...] Read more.

Chiral tertiary and quaternary amine solvating agents for NMR spectroscopy were synthesized from the wood resin derivative (+)-dehydroabietylamine (2). The resolution of enantiomers of model compounds [Mosher’s acid (3) and its n-Bu₄N salt (4)] (guests) by (+)-dehydroabietyl-N,N-dimethylmethanamine (5) and its ten different ammonium salts (hosts) was studied. The best results with 3 were obtained using 5 while with 4 the best enantiomeric resolution was obtained using (+)-dehydroabietyl-N,N-dimethylmethanaminium bis(trifluoromethane-sulfonimide) (6). The compounds 5 and 6 showed a 1:1 complexation behaviour between the host and guest. The capability of 5 and 6 to recognize the enantiomers of various α-substituted carboxylic acids and their n-Bu₄N salts in enantiomeric excess (ee) determinations was demonstrated. A modification of the RES-TOCSY NMR pulse sequence is described, allowing the enhancement of enantiomeric discrimination when the resolution of multiplets is insufficient. Full article

(This article belongs to the Section Organic Chemistry)

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14 pages, 3642 KiB

Open AccessReview

Quaternary Alkylammonium Conjugates of Steroids: Synthesis, Molecular Structure, and Biological Studies

by Bogumił Brycki^*, Hanna Koenig and Tomasz Pospieszny

Laboratory of Microbiocides Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland

Molecules 2015, 20(11), 20887-20900; https://doi.org/10.3390/molecules201119735 - 23 Nov 2015

Cited by 15 | Viewed by 7975

Abstract

The methods of synthesis as well as physical, spectroscopic (¹H-NMR, ¹³C-NMR, and FT-IR, ESI-MS), and biological properties of quaternary and dimeric quaternary alkylammonium conjugates of steroids are presented. The results were contrasted with theoretical calculations (PM5 methods) and potential pharmacological [...] Read more.

The methods of synthesis as well as physical, spectroscopic (¹H-NMR, ¹³C-NMR, and FT-IR, ESI-MS), and biological properties of quaternary and dimeric quaternary alkylammonium conjugates of steroids are presented. The results were contrasted with theoretical calculations (PM5 methods) and potential pharmacological properties (PASS). Alkylammonium sterols exhibit a broad spectrum of antimicrobial activity comparable to squalamine. Full article

(This article belongs to the Section Organic Chemistry)

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11 pages, 2561 KiB

Open AccessArticle

Ultrasound-Assisted Extraction, Antioxidant and Anticancer Activities of the Polysaccharides from Rhynchosia minima Root

by Xuejing Jia, Chao Zhang, Jie Hu, Muxue He, Jiaolin Bao, Kai Wang, Peng Li, Meiwan Chen, Jianbo Wan, Huanxing Su, Qingwen Zhang and Chengwei He^*

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China

Molecules 2015, 20(11), 20901-20911; https://doi.org/10.3390/molecules201119734 - 23 Nov 2015

Cited by 22 | Viewed by 6898

Abstract

Box-Behnken design (BBD), one of the most common response surface methodology (RSM) methods, was used to optimize the experimental conditions for ultrasound-assisted extraction of polysaccharides from Rhynchosia minima root (PRM). The antioxidant abilities and anticancer activity of purified polysaccharide fractions were also measured. [...] Read more.

Box-Behnken design (BBD), one of the most common response surface methodology (RSM) methods, was used to optimize the experimental conditions for ultrasound-assisted extraction of polysaccharides from Rhynchosia minima root (PRM). The antioxidant abilities and anticancer activity of purified polysaccharide fractions were also measured. The results showed that optimal extraction parameters were as follows: ultrasound exposure time, 21 min; ratio of water to material, 46 mL/g; ultrasound extraction temperature, 63 °C. Under these conditions, the maximum yield of PRM was 16.95% ± 0.07%. Furthermore, the main monosaccharides of purified fractions were Ara and Gal. PRM3 and PRM5 exhibited remarkable DPPH radical scavenging activities and reducing power in vitro. PRM3 showed strong inhibitory activities on the growth of MCF-7 cells in vitro. The above results indicate that polysaccharides from R. minima root have the potential to be developed as natural antioxidants and anticancer ingredients for the food and pharmaceutical industries. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 968 KiB

Open AccessArticle

New Flavones, a 2-(2-Phenylethyl)-4H-chromen-4-one Derivative, and Anti-Inflammatory Constituents from the Stem Barks of Aquilaria sinensis

by Sin-Ling Wang^1,†, Tsong-Long Hwang^2,3,4

, Mei-Ing Chung^1,†, Ping-Jyun Sung⁵

, Chih-Wen Shu⁶, Ming-Jen Cheng⁷ and Jih-Jung Chen^8,*

¹ School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

² Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan

³ Research Center for Industry of Human Ecology and Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan 33302, Taiwan

⁴ Immunology Consortium, Chang Gung Memorial Hospital, Taoyuan 33302, Taiwan

⁵ National Museum of Marine Biology and Aquarium, Pingtung 94450, Taiwan

⁶ Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan

⁷ Bioresource Collection and Research Center (BCRC), Food Industry Research and Development Institute (FIRDI), Hsinchu 30062, Taiwan

⁸ Department of Pharmacy, Tajen University, Pingtung 90741, Taiwan

^† These authors contributed equally to this work.

Molecules 2015, 20(11), 20912-20925; https://doi.org/10.3390/molecules201119736 - 24 Nov 2015

Cited by 40 | Viewed by 8098

Abstract

In the current study, two new flavones, 4′-O-geranyltricin (1) and 3′-O-geranylpolloin (2), and a new 2-(2-phenylethyl)-4H-chromen-4-one derivative, 7-hydroxyl-6-methoxy-2-(2-phenylethyl)chromone (3), have been isolated from the stem barks of A. sinensis, together [...] Read more.

In the current study, two new flavones, 4′-O-geranyltricin (1) and 3′-O-geranylpolloin (2), and a new 2-(2-phenylethyl)-4H-chromen-4-one derivative, 7-hydroxyl-6-methoxy-2-(2-phenylethyl)chromone (3), have been isolated from the stem barks of A. sinensis, together with 21 known compounds 4–24. The structures of new compounds 1–3 were determined through spectroscopic and MS analyses. Compounds 2, 3, 5, 6, and 8–10 exhibited inhibition (IC₅₀ ≤ 12.51 μM) of superoxide anion generation by human neutrophils in response to formyl-l-methionyl-l-leucyl-l-phenylalanine/cytochalasin B (fMLP/CB). Compounds 3, 6, 8, 10, and 19 inhibited fMLP/CB-induced elastase release with IC₅₀ values ≤ 15.25 μM. This investigation reveals bioactive isolates (especially 2, 3, 5, 6, 8, 9, 10, and 19) could be further developed as potential candidates for the treatment or prevention of various inflammatory diseases. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 3273 KiB

Open AccessCommunication

Synthesis, Crystal Structure, Absolute Configuration and Antitumor Activity of the Enantiomers of 5-Bromo-2-chloro-N-(1-phenylethyl)pyridine-3-sulfonamide

by Zhixu Zhou¹, Linwei Li¹, Ning Yan¹, Lei Du¹, Changshan Sun^2,* and Tiemin Sun^1,*

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

² Pharmacy Department, Shenyang Pharmaceutical University, Shenyang 110016, China

Molecules 2015, 20(11), 20926-20938; https://doi.org/10.3390/molecules201119740 - 24 Nov 2015

Cited by 5 | Viewed by 6272

Abstract

Pyridinesulfonamide is an important fragment which has a wide range of applications in novel drugs. R- and S-isomers of 5-bromo-2-chloro-N-(1-phenylethyl)pyridine-3-sulfonamide have been synthesized, and the stereostructures have been researched. Single crystals of both compounds were obtained for X-ray analysis, [...] Read more.

Pyridinesulfonamide is an important fragment which has a wide range of applications in novel drugs. R- and S-isomers of 5-bromo-2-chloro-N-(1-phenylethyl)pyridine-3-sulfonamide have been synthesized, and the stereostructures have been researched. Single crystals of both compounds were obtained for X-ray analysis, and the absolute configurations (ACs) have been further confirmed by electronic circular dichroism (ECD), optical rotation (OR) and quantum chemical calculations. The crystal structures and calculated geometries were extremely similar, which permitted a comparison of the relative reliabilities of ACs obtained by ECD analyses and theoretical simulation. In addition, the effect of stereochemistry on the PI3Kα kinase and anticancer activity were investigated. Compounds 10a and 10b inhibit the activity of PI3Kα kinase with IC₅₀ values of 1.08 and 2.69 μM, respectively. Furthermore, molecular docking was performed to analyze the binding modes of R- and S-isomers. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 2184 KiB

Open AccessArticle

Clones of FeSOD, MDHAR, DHAR Genes from White Clover and Gene Expression Analysis of ROS-Scavenging Enzymes during Abiotic Stress and Hormone Treatments

by Yan Zhang, Zhou Li, Yan Peng^*, Xiaojuan Wang, Dandan Peng, Yaping Li, Xiaoshuang He, Xinquan Zhang^*, Xiao Ma, Linkai Huang

and Yanhong Yan

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

Molecules 2015, 20(11), 20939-20954; https://doi.org/10.3390/molecules201119741 - 24 Nov 2015

Cited by 65 | Viewed by 8295 | Correction

Abstract

Increased transcriptional levels of genes encoding antioxidant enzymes play important protective roles in coping with excessive accumulation of reactive oxygen species (ROS) in plants exposed to various abiotic stresses. To fully elucidate different evolutions and functions of ROS-scavenging enzymatic genes, we isolated iron [...] Read more.

Increased transcriptional levels of genes encoding antioxidant enzymes play important protective roles in coping with excessive accumulation of reactive oxygen species (ROS) in plants exposed to various abiotic stresses. To fully elucidate different evolutions and functions of ROS-scavenging enzymatic genes, we isolated iron superoxide dismutase (FeSOD), dehydroascorbate reductase (DHAR) and monodehydroascorbate reductase (MDHAR) from white clover for the first time and subsequently tested dynamic expression profiles of these genes together with previously identified other antioxidant enzyme genes including copper zinc superoxide dismutase (Cu/ZnSOD), manganese superoxide dismutase (MnSOD), glutathione reductase (GR), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) in response to cold, drought, salinity, cadmium stress and exogenous abscisic acid (ABA) or spermidine (Spd) treatment. The cloned fragments of FeSOD, DHAR and MDHAR genes were 630, 471 and 669 bp nucleotide sequences encoding 210, 157 and 223 amino acids, respectively. Phylogenetic analysis indicated that both amino acid and nucleotide sequences of these three genes are highly conservative. In addition, the analysis of genes expression showed the transcription of GR, POD, MDHAR, DHAR and Cu/ZnSOD were rapidly activated with relatively high abundance during cold stress. Differently, CAT, APX, FeSOD, Cu/ZnSOD and MnSOD exhibited more abundant transcripts compared to others under drought stress. Under salt stress, CAT was induced preferentially (3–12 h) compared to GR which was induced later (12–72 h). Cadmium stress mainly up-regulated Cu/ZnSOD, DHAR and MDHAR. Interestingly, most of genes expression induced by ABA or Spd happened prior to various abiotic stresses. The particular expression patterns and different response time of these genes indicated that white clover differentially activates genes encoding antioxidant enzymes to mitigate the damage of ROS during various environmental stresses. Full article

(This article belongs to the Section Bioorganic Chemistry)

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