Exploring the newer oxadiazoles as real inhibitors of human SIRT2 in hepatocellular cancer cells |
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| Affiliation: | 1. Laboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysore 570006, India;2. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600, Singapore;3. Adichunchanagiri Institute for Molecular Medicine, BG Nagara-571448, NagamangalaTaluk, Mandya District, India;4. Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570006, India;1. Department of Physics, University College of Science, Tumkur University, Tumakuru, 570 103, India;2. Department of Studies in Physics, University of Mysore, Manasagangotri, Mysuru, 570 006, India;1. Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan;2. Division of Anaerobe Research, Life Science Research Center, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan;3. United Graduate School of Drug Discovery and Medicinal Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan;4. College of Science and Technology, Nihon University, Chiyoda, Tokyo 101-0062, Japan;1. Université de Paris, CiTCoM, 8038 CNRS, U 1268 INSERM, F-75006, Paris, France;2. China International Science and Technology, Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, 300457, China;3. Service Biologie Du Médicament, Toxicologie, AP-HP, Hôpital Cochin, F-75014, Paris, France;4. Université de Paris, CiTCoM, 8038 CNRS, Paris, F-75006, France;1. Department of Chemistry and Molecular Biology, Medicinal Chemistry, University of Gothenburg, SE-412 96 Göteborg, Sweden;2. School of Pharmacy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland;3. Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI- 00014 Helsinki, Finland |
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| Abstract: | A novel series of indazole tethered oxadiazoles (OTDs) derivatives were synthesized, characterized and screened for their anti-proliferative activity against hepatocellular carcinoma (HCC) cells. OTDs structure was further confirmed by Single-crystal X-ray diffraction studies. Among the tested OTDs, compound 2-(4-methoxyphenyl)-5-(1-methyl-1H-indazol-3-yl)-1,3,4-oxadiazole was found to inhibit the catalytical activity of SIRT2 and brings about apoptosis as shown by western blot analysis and flow cytometry data. Also, the tested OTDs were found to interact with the active site of human SIRT2 in silico but not with the cavity of co-crystal ligand 5-(3- hydroxypropyl)-3-(4-chlorophenyl)-1,2,4-oxadiazole, which indicate that these OTDs has potential in the development of SIRT2 inhibitors in liver cancer models. |
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| Keywords: | SIRT2 Indazole Oxadiazole HCC Drug-discovery |
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