Synthesis,Molecular Docking and Preliminary Antileukemic Activity of 4-Methoxybenzyl Derivatives Bearing Imidazo[2,1-b][1,3,4]thiadiazole |
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| Authors: | B Choodamani Karla G Cano Hernandez Sujeet Kumar Ann Maria Tony Austre Y Schiaffino Bustamante Renato J Aguilera Dominique Schols C Gopi Mohan Subhas S Karki |
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| Institution: | 1. Department of Pharmaceutical Chemistry, KLE College of Pharmacy (A Constituent Unit of KAHER-Belagavi), Bengaluru, 560010 Karnataka, India;2. The Cellular Characterization and Biorepository Core Facility and Border Biomedical Research Center and Department of Biological Sciences, The University of Texas at El Paso, El Paso, 79968 TX, USA;3. Center for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham, Kochi, 682041 Kerala, India;4. Rega Institute for Medical Research, Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, KU Leuven, B-3000 Leuven, Belgium |
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| Abstract: | In this study, we synthesized 22 compounds in a series with various substitution on imidazo2,1-b]1,3,4]thiadiazole. The potential cytotoxic activity of these compounds investigated in leukemia cell lines by Differential Nuclear Staining (DNS). Our results identified two compounds, 2-(4-methoxybenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo2,1-b]1,3,4]thiadiazol-5-yl thiocyanate and 6-(4-chlorophenyl)-2-(4-methoxybenzyl)imidazo2,1-b]1,3,4]thiadiazole-5-carbaldehyde, exhibited the most cytotoxic effect against murine leukemia cells (L1210), human T-lymphocyte cells (CEM) and human cervix carcinoma cells (HeLa) with IC50 values ranging between 0.79 and 1.6 μM. The results indicate that 2-(4-methoxybenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo2,1-b]1,3,4]thiadiazol-5-yl thiocyanate is inducing phosphatidylserine externalization and caspase-3 activation which are both a hallmark of apoptosis. Docking studies showed that 2-(4-methoxybenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo2,1-b]1,3,4]thiadiazol-5-yl thiocyanate binds within the active sites of transforming growth factor beta (TGF-β) type I receptor kinase domain by strong hydrogen binding and hydrophobic interactions. |
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| Keywords: | imidazothiadiazole cytotoxicity TGF beta receptor kinase melphalan levamisole |
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