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Synthesis, Molecular Docking and Preliminary Antileukemic Activity of 4‐Methoxybenzyl Derivatives Bearing Imidazo[2,1‐ b ][1,3,4]thiadiazole
Author(s) -
Choodamani B.,
Cano Hernandez Karla G.,
Kumar Sujeet,
Tony Ann Maria,
Schiaffino Bustamante Austre Y.,
Aguilera Renato J.,
Schols Dominique,
Gopi Mohan C.,
Karki Subhas S.
Publication year - 2021
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.202000800
Subject(s) - chemistry , stereochemistry , hela , docking (animal) , cytotoxic t cell , thiocyanate , biochemistry , in vitro , medicine , nursing
In this study, we synthesized 22 compounds in a series with various substitution on imidazo[2,1‐ 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‐2 H ‐chromen‐3‐yl)imidazo[2,1‐ b ][1,3,4]thiadiazol‐5‐yl thiocyanate and 6‐(4‐chlorophenyl)‐2‐(4‐methoxybenzyl)imidazo[2,1‐ 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 IC 50 values ranging between 0.79 and 1.6 μM. The results indicate that 2‐(4‐methoxybenzyl)‐6‐(2‐oxo‐2 H ‐chromen‐3‐yl)imidazo[2,1‐ 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‐2 H ‐chromen‐3‐yl)imidazo[2,1‐ 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.