12 pages, 312 KiB  
Article
Antioxidant and Anticancer Constituents from the Leaves of Liriodendron tulipifera
by Ya-Fei Kang 1, Chi-Ming Liu 2, Chiu-Li Kao 1,2 and Chung-Yi Chen 3,*
1 Department of Health Beauty, School of Medical and Health Sciences, Fooyin University, Ta-Liao District, Kaohsiung 83102, Taiwan
2 Tzu Hui Institute of Technology, Pingtung County 92641, Taiwan
3 Department of Nutrition and Health Science, School of Medical and Health Sciences, Fooyin University, Ta-Liao District, Kaohsiung 83102, Taiwan
Molecules 2014, 19(4), 4234-4245; https://doi.org/10.3390/molecules19044234 - 3 Apr 2014
Cited by 42 | Viewed by 8248
Abstract
Sixteen compounds were extracted and purified from the leaves of Liriodendron tulipifera. These compounds include aporphines, oxoaporphine, coumarin, sesquiterpene lactone, benzenoids, cyclitol and steroids. (+)-Norstephalagine (2) (an aporphine) and scopoletin (8) (a coumarin) were isolated from Liriodendron tulipifera [...] Read more.
Sixteen compounds were extracted and purified from the leaves of Liriodendron tulipifera. These compounds include aporphines, oxoaporphine, coumarin, sesquiterpene lactone, benzenoids, cyclitol and steroids. (+)-Norstephalagine (2) (an aporphine) and scopoletin (8) (a coumarin) were isolated from Liriodendron tulipifera leaves from the first time. The identified compounds were screened for their antiradical scavenging, metal chelating and ferric reducing power activities. The results have showed that these compounds have antioxidative activity. The study has also examined the chemopreventive property of the isolated compounds against human melanoma cells A375. The results shown that (−)-anonaine (1), (−)-liridinine (3), (+)-lirinidine (6), lysicamine (7) and epitulipinolide diepoxide (9) significantly inhibited the proliferation of melanoma cells. These results revealed that these compounds have antioxidative activity and chemopreventive activity in skin melanoma cells. Full article
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
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22 pages, 820 KiB  
Article
Synthesis, Spectroscopic and Theoretical Studies of New Quaternary N,N-Dimethyl-3-phthalimidopropylammonium Conjugates of Sterols and Bile Acids
by Bogumil Brycki *, Hanna Koenig, Iwona Kowalczyk and Tomasz Pospieszny *
Laboratory of Microbiocide Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka 6, Poznań 60-780, Poland
Molecules 2014, 19(4), 4212-4233; https://doi.org/10.3390/molecules19044212 - 3 Apr 2014
Cited by 12 | Viewed by 6907
Abstract
New quaternary 3-phthalimidopropylammonium conjugates of steroids were obtained by reaction of sterols (ergosterol, cholesterol, cholestanol) and bile acids (lithocholic, deoxycholic, cholic) with bromoacetic acid bromide to give sterol 3β-bromoacetates and bile acid 3α-bromoacetates, respectively. These intermediates were subjected to nuclephilic substitution with N [...] Read more.
New quaternary 3-phthalimidopropylammonium conjugates of steroids were obtained by reaction of sterols (ergosterol, cholesterol, cholestanol) and bile acids (lithocholic, deoxycholic, cholic) with bromoacetic acid bromide to give sterol 3β-bromoacetates and bile acid 3α-bromoacetates, respectively. These intermediates were subjected to nuclephilic substitution with N,N-dimethyl-3-phthalimidopropylamine to give the final quaternary ammonium salts. The structures of products were confirmed by spectral (1H-NMR, 13C-NMR, and FT-IR) analysis, mass spectrometry (ESI-MS, MALDI) as well as PM5 semiempirical methods and B3LYP ab initio methods. Estimation of the pharmacotherapeutic potential has been accomplished for synthesized compounds on the basis of Prediction of Activity Spectra for Substances (PASS). Full article
(This article belongs to the Section Organic Chemistry)
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12 pages, 224 KiB  
Article
Antiprotozoal Activities of Millettia richardiana (Fabaceae) from Madagascar
by Manitriniaina Rajemiarimiraho 1,2,3, Jean-Théophile Banzouzi 2,4,*, Marie-Laure Nicolau-Travers 5,6,7, Suzanne Ramos 4, Zakaria Cheikh-Ali 8, Christian Bories 8, Olga L. Rakotonandrasana 2, Stéphane Rakotonandrasana 1, Philippe Antoine Andrianary 3 and Françoise Benoit-Vical 5,6,7,*
1 Centre National d'Application de la Recherche Pharmaceutique (CNARP), BP 702 Antananarivo 101, Madagascar, France
2 Centre d'Etude et de Recherche Médecins d'Afrique (CERMA), 43, rue des Glycines, 91600 Savigny sur Orge, France
3 Ecole Supérieure Polytechnique d'Antananarivo (ESPA), Université d'Antananarivo, BP 1500, Antananarivo 101, Madagascar
4 Institut de Chimie des Substances Naturelles (ICSN-CNRS), Bâtiment 27, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France
5 CNRS/LCC (Laboratoire de Chimie de Coordination) UPR8241, 205, route de Narbonne, F-31077 Toulouse, France
6 Université de Toulouse III, UPS, LCC; 118, route de Narbonne, F-31077 Toulouse, France
7 Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire de Rangueil, Université de Toulouse et Faculté de Médecine de Rangueil, Université de Toulouse III, UPS, TSA 50032, 31059 Toulouse cedex 9, France
8 Laboratoire de Pharmacognosie et de Chimiothérapie Antiparasitaire, CNRS UMR 8076 BioCIS, Faculté de Pharmacie, 5 rue J.-B. Clément, Université Paris-Sud 11, 92296 Châtenay-Malabry, France
Molecules 2014, 19(4), 4200-4211; https://doi.org/10.3390/molecules19044200 - 3 Apr 2014
Cited by 8 | Viewed by 7641
Abstract
With at least 60% of the Millettia species (Fabaceae) being in medicinal use, we found it relevant to assess the potential antiprotozoal and antifungal activities of Millettia richardiana. Water and methanol crude extracts of the stem barks from M. richardiana and the six [...] Read more.
With at least 60% of the Millettia species (Fabaceae) being in medicinal use, we found it relevant to assess the potential antiprotozoal and antifungal activities of Millettia richardiana. Water and methanol crude extracts of the stem barks from M. richardiana and the six fractions resulting from the fractionation of the methanol extract were tested. The dichloromethane extracted fraction showed the best in vitro antiprotozoal activities (IC50 = 5.8 μg/mL against Plasmodium falciparum, 11.8 μg/mL against Leishmania donovani and 12.8 μg/mL against Trypanosoma brucei brucei) as well as low cytotoxicity on several cell lines. The phytochemical analysis showed this selected fraction to be rich in terpenoids and alkaloids, which could explain its antiparasitic activity. A phytochemical study revealed the presence of lonchocarpenin, betulinic acid, β-amyrin, lupeol, palmitic acid, linoleic acid and stearic acid, among which betulinic acid and lupeol could be the compounds responsible of these antiprotozoal activities. By contrast, neither the crude extracts nor the fractions showed antifungal activity against Candida. These results confirm the importance of the genus Millettia in Malagasy ethnomedicine, its potential use in antiparasitic therapy, and the interest of developing a sustainable exploitation of this plant. Moreover, both molecules betulinic acid and lupeol appeared as very relevant molecules for their antiprotozoal properties. Full article
11 pages, 300 KiB  
Article
Agaricus Blazei Hot Water Extract Shows Anti Quorum Sensing Activity in the Nosocomial Human Pathogen Pseudomonas Aeruginosa
by Marina Soković 1, Ana Ćirić 1, Jasmina Glamočlija 1, Miloš Nikolić 1 and Leo J. L. D. Van Griensven 2,*
1 Department of Plant Physiology, Institute for Biological Research "Siniša Stanković", University of Belgrade, Bulevar Despota Stefana 142, Belgrade 11000, Serbia
2 Plant Research International, Wageningen University and Research Centre, Droevendaalsesteeg 1, Wageningen 6700 AA, The Netherlands
Molecules 2014, 19(4), 4189-4199; https://doi.org/10.3390/molecules19044189 - 3 Apr 2014
Cited by 49 | Viewed by 9463
Abstract
The edible mushroom Agaricus blazei Murill is known to induce protective immunomodulatory action against a variety of infectious diseases. In the present study we report potential anti-quorum sensing properties of A. blazei hot water extract. Quorum sensing (QS) plays an important role in [...] Read more.
The edible mushroom Agaricus blazei Murill is known to induce protective immunomodulatory action against a variety of infectious diseases. In the present study we report potential anti-quorum sensing properties of A. blazei hot water extract. Quorum sensing (QS) plays an important role in virulence, biofilm formation and survival of many pathogenic bacteria, including the Gram negative Pseudomonas aeruginosa, and is considered as a novel and promising target for anti-infectious agents. In this study, the effect of the sub-MICs of Agaricus blazei water extract on QS regulated virulence factors and biofilm formation was evaluated against P. aeruginosa PAO1. Sub-MIC concentrations of the extract which did not kill P. aeruginosa nor inhibited its growth, demonstrated a statistically significant reduction of virulence factors of P. aeruginosa, such as pyocyanin production, twitching and swimming motility. The biofilm forming capability of P. aeruginosa was also reduced in a concentration-dependent manner at sub-MIC values. Water extract of A. blazei is a promising source of antiquorum sensing and antibacterial compounds. Full article
(This article belongs to the Section Natural Products Chemistry)
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32 pages, 1023 KiB  
Article
Bondonic Effects in Group-IV Honeycomb Nanoribbons with Stone-Wales Topological Defects
by Mihai V. Putz 1,* and Ottorino Ori 1,2
1 Laboratory of Computational and Structural Physical-Chemistry for Nanosciences and QSAR, Biology-Chemistry Department, Faculty of Chemistry, Biology, Geography, West University of Timişoara, Pestalozzi Street No.16, Timişoara, RO-300115, Romania
2 Actinium Chemical Research, Via Casilina 1626/A, Rome 00133, Italy
Molecules 2014, 19(4), 4157-4188; https://doi.org/10.3390/molecules19044157 - 3 Apr 2014
Cited by 32 | Viewed by 7692
Abstract
This work advances the modeling of bondonic effects on graphenic and honeycomb structures, with an original two-fold generalization: (i) by employing the fourth order path integral bondonic formalism in considering the high order derivatives of the Wiener topological potential of those 1D systems; [...] Read more.
This work advances the modeling of bondonic effects on graphenic and honeycomb structures, with an original two-fold generalization: (i) by employing the fourth order path integral bondonic formalism in considering the high order derivatives of the Wiener topological potential of those 1D systems; and (ii) by modeling a class of honeycomb defective structures starting from graphene, the carbon-based reference case, and then generalizing the treatment to Si (silicene), Ge (germanene), Sn (stannene) by using the fermionic two-degenerate statistical states function in terms of electronegativity. The honeycomb nanostructures present η-sized Stone-Wales topological defects, the isomeric dislocation dipoles originally called by authors Stone-Wales wave or SWw. For these defective nanoribbons the bondonic formalism foresees a specific phase-transition whose critical behavior shows typical bondonic fast critical time and bonding energies. The quantum transition of the ideal-to-defect structural transformations is fully described by computing the caloric capacities for nanostructures triggered by η-sized topological isomerisations. Present model may be easily applied to hetero-combinations of Group-IV elements like C-Si, C-Ge, C-Sn, Si-Ge, Si-Sn, Ge-Sn. Full article
(This article belongs to the Special Issue Quantum Information in Molecular Structures and Nanosystems)
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12 pages, 2814 KiB  
Article
Optical Absorption of the Antitrypanocidal Drug Benznidazole inWater
by Eveline M. Bezerra 1, João R. Bezerra-Neto 2, Francisco A. M. Sales 3, Ricardo P. Dos Santos 3, Alice M. C. Martins 1, Pedro De Lima-Neto 2, Ewerton W. S. Caetano 4,*, Eudenilson L. Albuquerque 5 and Valder N. Freire 3
1 Departamento de Análises Clínicas e Toxicológicas, Universidade Federal do Ceará, Campus do Porangabuçu, Fortaleza 60430-270, CE, Brazil
2 Departamento de Química Analítica e Fisico-Química, Universidade Federal do Ceará, Campus do Pici, Fortaleza 60440-900, CE, Brazil
3 Departamento de Física, Universidade Federal do Ceará, Campus do Pici, Caixa Postal 6030,Fortaleza 60440-900, CE, Brazil
4 Instituto Federal de Educação, Ciência e Tecnologia do Ceará, Av. Treze de Maio, 2081, Benfica,Fortaleza 60040-531, CE, Brazil
5 Departamento de Biofísica e Farmacologia, Universidade Federal do Rio Grande do Norte, Natal-RN 59072-970, Brazil
Molecules 2014, 19(4), 4145-4156; https://doi.org/10.3390/molecules19044145 - 2 Apr 2014
Cited by 13 | Viewed by 7134
Abstract
UV-vis optical absorption spectra of the antitrypanocidal drug benznidazole solvated in water were measured for various concentrations. The spectra show a prominent peak around 3.80 eV, while deconvolution of the UV-vis optical absorption spectra revealed six bands centered at 3.60, 3.83, 4.15, 4.99, [...] Read more.
UV-vis optical absorption spectra of the antitrypanocidal drug benznidazole solvated in water were measured for various concentrations. The spectra show a prominent peak around 3.80 eV, while deconvolution of the UV-vis optical absorption spectra revealed six bands centered at 3.60, 3.83, 4.15, 4.99, 5.60, and 5.76 eV. Benznidazole electronic transitions were obtained after density functional theory (DFT) calculations within the polarized continuum (PCM) model for water solvation. Molecular geometry optimizations were carried out, and the measured absorption peaks were related to specific molecular orbital transitions obtained within the time dependent DFT (TD-DFT) with excellent agreement between theory and experiment. Full article
(This article belongs to the Section Medicinal Chemistry)
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10 pages, 474 KiB  
Article
Turn-on Type Chemical Sensing of Vitamin K4 by Fluorene Dendrimers with Naphthalene Segments
by Naoya Adachi 1,*, Hiroki Sugiyama 2, Masafumi Arai 2 and Hideo Ogawa 2
1 Division of Liberal Arts, School of Science and Engineering, Tokyo Denki University, Hatoyama, Hiki-gun, Saitama 350-0394, Japan
2 Division of Science, School of Science and Engineering, Tokyo Denki University, Hatoyama, Hiki-gun, Saitama 350-0394, Japan
Molecules 2014, 19(4), 4135-4144; https://doi.org/10.3390/molecules19044135 - 2 Apr 2014
Cited by 3 | Viewed by 6765
Abstract
G1 and G2 fluorene dendrimers with naphthalene termini were synthesized as a fluorescence turn-on type chemical sensor for vitamin K4. The fluorene dendrimers were prepared by Williamson ether reaction between the fluorene core with dihydroxy groups and dendritic naphthalene segments with methylene chloride [...] Read more.
G1 and G2 fluorene dendrimers with naphthalene termini were synthesized as a fluorescence turn-on type chemical sensor for vitamin K4. The fluorene dendrimers were prepared by Williamson ether reaction between the fluorene core with dihydroxy groups and dendritic naphthalene segments with methylene chloride by a convergent method. We investigated the relationship between the dendrimer generation and vitamin K4 recognition of fluorene dendrimer with naphthalene termini in CHCl3. Addition of vitamin K4 enhanced the fluorescence intensity of the fluorene dendrimer. Especially, the G2 fluorene dendrimer was found to be an effective chemical sensor for vitamin K4 and better than the G1 fluorene dendrimer. Full article
(This article belongs to the Special Issue Fluorescent Probes)
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20 pages, 1001 KiB  
Article
Chemo-Enzymatic Synthesis of Silybin and 2,3-Dehydrosilybin Dimers
by Eva Vavříková 1, Jan Vacek 2, Kateřina Valentová 1,2, Petr Marhol 1, Jitka Ulrichová 2, Marek Kuzma 1 and Vladimír Křen 1,*
1 Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ-142 20 Prague 4, Czech Republic
2 Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, CZ-775 15 Olomouc, Czech Republic
Molecules 2014, 19(4), 4115-4134; https://doi.org/10.3390/molecules19044115 - 2 Apr 2014
Cited by 21 | Viewed by 8507
Abstract
Divalent or multivalent molecules often show enhanced biological activity relative to the simple monomeric units. Here we present enzymatically and chemically prepared dimers of the flavonolignans silybin and 2,3-dehydrosilybin. Their electrochemical behavior was studied by in situ and ex situ square wave voltammetry. [...] Read more.
Divalent or multivalent molecules often show enhanced biological activity relative to the simple monomeric units. Here we present enzymatically and chemically prepared dimers of the flavonolignans silybin and 2,3-dehydrosilybin. Their electrochemical behavior was studied by in situ and ex situ square wave voltammetry. The oxidation of monomers and dimers was similar, but adsorption onto the electrode and cell surfaces was different. A 1,1-diphenyl-2-picrylhydrazyl (DPPH) and an inhibition of microsomal lipoperoxidation assay were performed with same trend of results for silybin and 2,3-dehydrosilybin dimers. Silybin dimer showed better activity than the monomer, while on the contrary 2,3-dehydrosilybin dimer presented weaker antioxidant/antilipoperoxidant activity than its monomer. Cytotoxicity was evaluated on human umbilical vein endothelial cells, normal human adult keratinocytes, mouse fibroblasts (BALB/c 3T3) and human liver hepatocellular carcinoma cell line (HepG2). Silybin dimer was more cytotoxic than the parent compound and in the case of 2,3-dehydrosilybin its dimer showed weaker cytotoxicity than the monomer. Full article
(This article belongs to the Section Natural Products Chemistry)
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10 pages, 632 KiB  
Article
Fluorescent Probes for Insect Ryanodine Receptors: Candidate Anthranilic Diamides
by Yi Wang 1, Lei Guo 2, Suzhen Qi 1,3, Hao Zhang 1, Kechang Liu 1, Ruiquan Liu 1, Pei Liang 2, John E. Casida 3 and Shangzhong Liu 1,*
1 Department of Applied Chemistry, College of Science, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China
2 College of Agriculture and Biotechnology, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China
3 Department of Environmental Science, Policy, and Management, University of California, Berkeley, CA 94720-3112, USA
Molecules 2014, 19(4), 4105-4114; https://doi.org/10.3390/molecules19044105 - 2 Apr 2014
Cited by 10 | Viewed by 7955
Abstract
Diamide insecticides with high efficacy against pests and good environmental safety are broadly applied in crop protection. They act at a poorly-defined site in the very complex ryanodine (Ry) receptor (RyR) potentially accessible to a fluorescent probe. Two N-propynyl analogs of the [...] Read more.
Diamide insecticides with high efficacy against pests and good environmental safety are broadly applied in crop protection. They act at a poorly-defined site in the very complex ryanodine (Ry) receptor (RyR) potentially accessible to a fluorescent probe. Two N-propynyl analogs of the major anthranilic diamide insecticides chlorantraniliprole (Chlo) and cyantraniliprole (Cyan) were accordingly synthesized and converted into two fluorescent ligands by click reaction coupling with 3-azido-7-hydroxy-2H-chromen-2-one. The new diamide analogs and fluorescent ligands were shown to be nearly as potent as Chlo and Cyan in inhibition of [3H]Chlo binding and stimulation of [3H]Ry binding in house fly thoracic muscle RyR. Although the newly synthesized compounds had only moderate activity in insect larvicidal activity assays, their high in vitro potency in a validated insect RyR binding assay encourages further development of fluorescent probes for insect RyRs. Full article
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22 pages, 364 KiB  
Article
Simultaneous Determination of Original, Degraded Ginsenosides and Aglycones by Ultra High Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Mass Spectrometry for Quantitative Evaluation of Du-Shen-Tang, the Decoction of Ginseng
by Shan-Shan Zhou 1,2,†, Jin-Di Xu 1,†, He Zhu 1, Hong Shen 1, Jun Xu 1, Qian Mao 1, Song-Lin Li 1,* and Ru Yan 3,*
1 Department of Pharmaceutical Analysis and Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing 210028, China
2 College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China
3 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
These authors contributed equally to this work.
Molecules 2014, 19(4), 4083-4104; https://doi.org/10.3390/molecules19044083 - 2 Apr 2014
Cited by 20 | Viewed by 6699
Abstract
In the present study, an ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) method for simultaneous determination of eleven original, fourteen degraded ginsenosides and five aglycones was developed and validated to quantitatively evaluate the transformation of ginsenosides during preparation of [...] Read more.
In the present study, an ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) method for simultaneous determination of eleven original, fourteen degraded ginsenosides and five aglycones was developed and validated to quantitatively evaluate the transformation of ginsenosides during preparation of Du-Shen-Tang, the decoction of ginseng. Both positive and negative modes as well as the step wave ion transfer optics technology were used to increase the detection sensitivity of QTOF-MS. The extracting ion mode based on the quasi-molecular ions, molecular ions and fragment ions characteristic to each analyte was used to increase the selectivity for quantitative analysis. Under the optimized UHPLC and QTOF-MS conditions, the 30 analytes with different polarities were separated (except for Re and Rg1) within 26 min. The developed method was applied for the quantitative comparison of Du-Shen-Tang and its raw materials derived from Asian ginseng (ASG) and American ginseng (AMG), respectively. It was found that the contents of the original ginsenosides decreased from 26,053.09 to 19,393.29 μg/g or 45,027.72 to 41,865.39 μg/g, whereas the degraded ginsenosides and aglycones increased from 159.72 to 685.37 μg/g or 676.54 to 1,502.26 μg/g in Du-Shen-Tang samples of ASG or AMG when compared with their raw materials, indicating that decocting could dramatically increase the proportion of the less polar degraded ginsenosides in Du-Shen-Tang. Whether these changed proportions of different polar ginsenosides could affect the bioactivities of the decoctions and their raw materials derived from ASG and AMG deserves further investigation. Full article
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7 pages, 202 KiB  
Communication
A One-Step Microwave-Assisted Synthetic Method for an O/S-Chemoselective Route to Derivatives of the First Adenosine A3 PET Radiotracer
by Karem Shanab 1,*,†, Catharina Neudorfer 2,†, Wolfgang Holzer 2, Markus Mitterhauser 1, Wolfgang Wadsak 1 and Helmut Spreitzer 2
1 Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
2 Department of Pharmaceutical Chemistry, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria
These authors contributed equally to this work.
Molecules 2014, 19(4), 4076-4082; https://doi.org/10.3390/molecules19044076 - 2 Apr 2014
Viewed by 5234
Abstract
The synthesis of reference standards and expected in vivo metabolites of the first adenosine A3 PET radiotracer [18F]FE@SUPPY ([18F]fluoroethyl 4,6-diethyl-5-[(ethyl-sulfanyl)carbonyl]-2-phenylpyridine-3-carboxylate) was achieved by using a straightforward microwave assisted alkylation method, which allowed O/S-chemoselective alkylation of the starting material 1 [...] Read more.
The synthesis of reference standards and expected in vivo metabolites of the first adenosine A3 PET radiotracer [18F]FE@SUPPY ([18F]fluoroethyl 4,6-diethyl-5-[(ethyl-sulfanyl)carbonyl]-2-phenylpyridine-3-carboxylate) was achieved by using a straightforward microwave assisted alkylation method, which allowed O/S-chemoselective alkylation of the starting material 1 to give each target compound 28 in a single step. Full article
(This article belongs to the Section Medicinal Chemistry)
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18 pages, 800 KiB  
Article
Determination of Bioactive Components in Chinese Herbal Formulae and Pharmacokinetics of Rhein in Rats by UPLC-MS/MS
by Mei-Ling Hou 1, Li-Wen Chang 1, Chi-Hung Lin 2, Lie-Chwen Lin 3 and Tung-Hu Tsai 1,4,5,*
1 Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, No. 155, Sec. 2, Li-Nong St, Beitou District, Taipei 11221, Taiwan
2 Institute of Microbiology and Immunology, National Yang-Ming University, No. 155, Sec. 2, Li-Nong St, Beitou District, Taipei 11221, Taiwan
3 National Research Institute of Chinese Medicine, No. 155-1, Sec. 2, Li-Nong St., Beitou District, Taipei 11221, Taiwan
4 Graduate Institute of Acupuncture Science, China Medical University, No. 91, Hsueh-Shih Road, Taichung 404, Taiwan
5 Department of Education and Research, Taipei City Hospital, No.145, Zhengzhou Rd., Datong Dist., Taipei 103, Taiwan
Molecules 2014, 19(4), 4058-4075; https://doi.org/10.3390/molecules19044058 - 2 Apr 2014
Cited by 30 | Viewed by 9060
Abstract
Rhein (4,5-dihydroxy-9,10-dioxoanthracene-2-carboxylic acid, cassic acid) is a pharmacological active component found in Rheum palmatum L. the major herb of San-Huang-Xie-Xin-Tang (SHXXT), a medicinal herbal product used as a remedy for constipation. Here we have determined multiple bioactive components in SHXXT and investigated the [...] Read more.
Rhein (4,5-dihydroxy-9,10-dioxoanthracene-2-carboxylic acid, cassic acid) is a pharmacological active component found in Rheum palmatum L. the major herb of San-Huang-Xie-Xin-Tang (SHXXT), a medicinal herbal product used as a remedy for constipation. Here we have determined multiple bioactive components in SHXXT and investigated the comparative pharmacokinetics of rhein in rats. A sensitive and specific method combining liquid chromatography with electrospray ionization tandem mass spectrometry has been developed and validated to simultaneously quantify six active compounds in the pharmaceutical herbal product SHXXT to further study their pharmacokinetics in rats. Multiple reaction monitoring (MRM) was employed for quantification with switching electrospray ion source polarity between positive and negative modes in a single run. There were no significant matrix effects in the quantitative analysis and the mean recovery for rhein in rat plasma was 91.6% ± 3.4%. The pharmacokinetic data of rhein demonstrate that the herbal formulae or the single herbal extract provide significantly higher absorption rate than the pure compound. This phenomenon suggests that the other herbal ingredients of SHXXT and rhubarb extract significantly enhance the absorption of rhein in rats. In conclusion, the herbal formulae (SHXXT) are more efficient than the single herb (rhubarb) or the pure compound (rhein) in rhein absorption. Full article
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12 pages, 303 KiB  
Article
Chemical Composition and Biological Activities of Gerbera anandria
by Fa He 1,2, Miao Wang 1,3, Minghuan Gao 1, Min Zhao 1, Yuhua Bai 2,* and Chunjie Zhao 1,*
1 Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, No. 103 Wenhua Road Shenhe District , Shenyang 110016, China
2 College of Pharmacy, Harbin Medical University, Daqing 163319, China
3 School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China
Molecules 2014, 19(4), 4046-4057; https://doi.org/10.3390/molecules19044046 - 2 Apr 2014
Cited by 38 | Viewed by 7680
Abstract
Gerbera anandria (Compositae) was extracted with 75% ethanol and the residue was fractionated using light petroleum, chloroform and ethyl acetate. The constituents of the extracts were separated by column chromatography employing solvents of different polarity. Column chromatography of the light petroleum fraction resulted [...] Read more.
Gerbera anandria (Compositae) was extracted with 75% ethanol and the residue was fractionated using light petroleum, chloroform and ethyl acetate. The constituents of the extracts were separated by column chromatography employing solvents of different polarity. Column chromatography of the light petroleum fraction resulted in the isolation of methyl hexadecanoate, while the chloroform fraction afforded xanthotoxin, 2-hydroxy-6-methylbenzoic acid, 7-hydroxy-1(3H)-isobenzofuranone, a mixture of β-sitosterol and stigmasterol, and 8-methoxysmyrindiol and the ethyl acetate fraction gave gerberinside, apigenin-7-O-β-d-glucopyranoside and quercetin. A new coumarin, 8-methoxysmyrindiol, was found. The chemical structures of the isolated compounds were established by MS and NMR (HSQC, HMBC). Free radical scavenging and cytotoxic activities of crude extracts and 8-methoxysmyrindiol were further investigated. The ethyl acetate phase exerted the strongest DPPH free radical scavenging activity in comparison to the other fractions. The coumarin 8-methoxysmyrindiol demonstrated cytotoxicity against multiple human cancer cell lines, with the highest potency in HepG2 cells. Full article
(This article belongs to the Section Natural Products Chemistry)
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25 pages, 4483 KiB  
Article
Computational Redesign of Bacterial Biotin Carboxylase Inhibitors Using Structure-Based Virtual Screening of Combinatorial Libraries
by Michal Brylinski 1,2,* and Grover L. Waldrop 1,2
1 Division of Biochemistry and Molecular Biology, Louisiana State University, Baton Rouge, LA 70803, USA
2 Center for Computation & Technology, Louisiana State University, Baton Rouge, LA 70803, USA
Molecules 2014, 19(4), 4021-4045; https://doi.org/10.3390/molecules19044021 - 2 Apr 2014
Cited by 11 | Viewed by 10202
Abstract
As the spread of antibiotic resistant bacteria steadily increases, there is an urgent need for new antibacterial agents. Because fatty acid synthesis is only used for membrane biogenesis in bacteria, the enzymes in this pathway are attractive targets for antibacterial agent development. Acetyl-CoA [...] Read more.
As the spread of antibiotic resistant bacteria steadily increases, there is an urgent need for new antibacterial agents. Because fatty acid synthesis is only used for membrane biogenesis in bacteria, the enzymes in this pathway are attractive targets for antibacterial agent development. Acetyl-CoA carboxylase catalyzes the committed and regulated step in fatty acid synthesis. In bacteria, the enzyme is composed of three distinct protein components: biotin carboxylase, biotin carboxyl carrier protein, and carboxyltransferase. Fragment-based screening revealed that amino-oxazole inhibits biotin carboxylase activity and also exhibits antibacterial activity against Gram-negative organisms. In this report, we redesigned previously identified lead inhibitors to expand the spectrum of bacteria sensitive to the amino-oxazole derivatives by including Gram-positive species. Using 9,411 small organic building blocks, we constructed a diverse combinatorial library of 1.2 × 108 amino-oxazole derivatives. A subset of 9 × 106 of these compounds were subjected to structure-based virtual screening against seven biotin carboxylase isoforms using similarity-based docking by eSimDock. Potentially broad-spectrum antibiotic candidates were selected based on the consensus ranking by several scoring functions including non-linear statistical models implemented in eSimDock and traditional molecular mechanics force fields. The analysis of binding poses of the top-ranked compounds docked to biotin carboxylase isoforms suggests that: (1) binding of the amino-oxazole anchor is stabilized by a network of hydrogen bonds to residues 201, 202 and 204; (2) halogenated aromatic moieties attached to the amino-oxazole scaffold enhance interactions with a hydrophobic pocket formed by residues 157, 169, 171 and 203; and (3) larger substituents reach deeper into the binding pocket to form additional hydrogen bonds with the side chains of residues 209 and 233. These structural insights into drug-biotin carboxylase interactions will be tested experimentally in in vitro and in vivo systems to increase the potency of amino-oxazole inhibitors towards both Gram-negative as well as Gram-positive species. Full article
(This article belongs to the Special Issue In-Silico Drug Design and In-Silico Screening)
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15 pages, 938 KiB  
Article
PBDE: Structure-Activity Studies for the Inhibition of Hepatitis C Virus NS3 Helicase
by Kazi Abdus Salam 1, Atsushi Furuta 2,3, Naohiro Noda 2,3, Satoshi Tsuneda 2, Yuji Sekiguchi 3, Atsuya Yamashita 4, Kohji Moriishi 4, Masamichi Nakakoshi 5, Hidenori Tani 6, Sona Rani Roy 7, Junichi Tanaka 7, Masayoshi Tsubuki 8,* and Nobuyoshi Akimitsu 1,*
1 Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
2 Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan
3 Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan
4 Department of Microbiology, Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan
5 Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan
6 Research Institute for Environmental Management Technology, National Institute of Advanced Industrial Science and Technology (AIST), 16-1, Onogawa, Tsukuba, Ibaraki 305-8569, Japan
7 Department of Chemistry, Biology and Marine Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan
8 Institute of Medical Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan
Molecules 2014, 19(4), 4006-4020; https://doi.org/10.3390/molecules19044006 - 2 Apr 2014
Cited by 8 | Viewed by 8087
Abstract
The helicase portion of the hepatitis C virus nonstructural protein 3 (NS3) is considered one of the most validated targets for developing direct acting antiviral agents. We isolated polybrominated diphenyl ether (PBDE) 1 from a marine sponge as an NS3 helicase inhibitor. In [...] Read more.
The helicase portion of the hepatitis C virus nonstructural protein 3 (NS3) is considered one of the most validated targets for developing direct acting antiviral agents. We isolated polybrominated diphenyl ether (PBDE) 1 from a marine sponge as an NS3 helicase inhibitor. In this study, we evaluated the inhibitory effects of PBDE (1) on the essential activities of NS3 protein such as RNA helicase, ATPase, and RNA binding activities. The structure-activity relationship analysis of PBDE (1) against the HCV ATPase revealed that the biphenyl ring, bromine, and phenolic hydroxyl group on the benzene backbone might be a basic scaffold for the inhibitory potency. Full article
(This article belongs to the Section Natural Products Chemistry)
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