Synthesis and biological evaluation of 1-benzyl-N-(2-(phenylamino)pyridin-3-yl)-1H-1,2,3-triazole-4-carboxamides as antimitotic agents |
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| Institution: | 1. Medicinal Chemistry and Biotechnology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India;2. Department of Chemistry, Osmania University, Hyderabad 500007, Telangana, India;3. School of Pharmaceutical Education and Research (SPER), Jamia Hamdard, 110 062 New Delhi, India;1. Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India;2. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India;1. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China;2. Department of Microbiology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, PR China;1. Department of Life and Environmental Sciences, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy;2. Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, SS554, 09042 Monserrato, Cagliari, Italy;3. Dipartimento di Scienze della Salute, Università Magna Graecia di Catanzaro, Campus “S. Venuta”, Viale Europa, 88100 Catanzaro, Italy;4. Department of Organic Chemistry, Semmelweis University, Hogyes Endre utca 7, H-1092 Budapest, Hungary;1. Department of Physics, Thanthai Periyar Government Institute of Technology, Vellore, 632002, Tamil Nadu, India;2. Department of Physics, Thanthai Periyar EVR Government Polytechnic College, Vellore, 632002, Tamil Nadu, India;3. Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai, 625021, Tamil Nadu, India;1. Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland;2. Laboratory of Molecular Basis of Cell Motility, Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093 Warsaw, Poland;1. Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland;2. Ludwik Hierszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wroc?aw, Poland;3. Institute of Low Temperature and Structure Research, Polish Academy of Sciences, PO Box 1410, 50-950 Wroc?aw, Poland;4. Department of Oncology, University of Alberta, Edmonton, Alberta T6G 1Z2, Canada;5. Institut für Medizinische Physik und Biophysik Charité – Universitätsmedizin Berlin, Campus Charité Mitte, Charitéplatz 1, 10117 Berlin, Germany |
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| Abstract: | A library of 1-benzyl-N-(2-(phenylamino)pyridin-3-yl)-1H-1,2,3-triazole-4-carboxamides (7a–al) have been designed, synthesized and screened for their anti-proliferative activity against some selected human cancer cell lines namely DU-145, A-549, MCF-7 and HeLa. Most of them have shown promising cytotoxicity against lung cancer cell line (A549), amongst them 7f was found to be the most potent anti-proliferative congener. Furthermore, 7f exhibited comparable tubulin polymerization inhibition (IC50 value 2.04 µM) to the standard E7010 (IC50 value 2.15 µM). Moreover, flow cytometric analysis revealed that this compound induced apoptosis via cell cycle arrest at G2/M phase in A549 cells. Induction of apoptosis was further observed by examining the mitochondrial membrane potential and was also confirmed by Hoechst staining as well as Annexin V-FITC assays. Furthermore, molecular docking studies indicated that compound 7f binds to the colchicine binding site of the β-tubulin. Thus, 7f exhibits anti-proliferative properties by inhibiting the tubulin polymerization through the binding at the colchicine active site and by induction of apoptosis. |
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| Keywords: | 2-Anilino-3-aminopyridines Triazole-4-carboxilic acids Apoptosis Cell cycle Colchicine binding Molecular docking Tubulin polymerization |
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