Synthesis,biological evaluation and molecular modeling of 1,3,4-thiadiazol-2-amide derivatives as novel antitubulin agents |
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| Institution: | 1. Research and Scientific Studies Unit, College of Nursing & Allied Health Sciences, Jazan University, Jazan 45142, Saudi Arabia;2. Industrial Biotechnology Laboratory, University Institute of Engineering & Technology, M.D. University Rohtak 124001, Haryana, India;3. Department of Clinical Nutrition, College of Applied Medical Sciences, University of Ha''il, Ha''il 2440, Saudi Arabia;4. Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia (A Central University), New Delhi110025, India;5. Department of Biosciences, Jamia Millia Islamia (A Central University), New Delhi 110025, India;6. Centre for Drug Research (CDR), Faculty of Pharmacy, Viikki Biocentre-2, University of Helsinki, PO Box 56 (Viikinkaari 5E), Helsinki FI-00014, Finland;1. Laboratory of Molecular Physiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland;1. College of Chemistry and Chemical Engineering, Key Laboratory of Hunan Forest Products and Chemical Industry Engineering, Jishou University, Jishou 416000, PR China;2. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China;1. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People’s Republic of China;2. School of Life Sciences, Shandong University of Technology, Shandong 255049, People’s Republic of China |
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| Abstract: | A series of 1,3,4-thiadiazol-2-amide derivatives (6a–w) were designed and synthesized as potential inhibitors of tubulin polymerization and as anticancer agents. The in vitro anticancer activities of these compounds were evaluated against three cancer cell lines by the MTT method. Among all the designed compounds, compound 6f exhibited the most potent anticancer activity against A549, MCF-7 and HepG2 cancer cell lines with IC50 values of 0.03 μM, 0.06 μM and 0.05 μM, respectively. Compound 6f also exhibited significant tubulin polymerization inhibitory activity (IC50 = 1.73 μM), which was superior to the positive control. The obtained results, along with a 3D-QSAR study and molecular docking that were used for investigating the probable binding mode, could provide an important basis for further optimization of compound 6f as a novel anticancer agent. |
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| Keywords: | 1 3 4-Thiadiazol-2-amide derivatives Tubulin polymerization inhibitors Anticancer activity Molecular docking 3D-QSAR |
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