Tanushree Banerjee, S. Sharma, N. Kapoor
Dec 1, 2011
Citations
2
Influential Citations
21
Citations
Journal
IUBMB Life
Abstract
Benzothiophene derivatives like benzothiophene sulphonamides, biphenyls, or carboxyls have been synthesized and have found wide pharmacological usage. Here we report, bromo‐benzothiophene carboxamide derivatives as potent, slow tight binding inhibitors of Plasmodium enoyl‐acyl carrier protein (ACP) reductase (PfENR). 3‐Bromo‐N‐(4‐fluorobenzyl)‐benzo[b]thiophene‐2‐carboxamide (compound 6) is the most potent inhibitor with an IC50 of 115 nM for purified PfENR. The inhibition constant (Ki) of compound 6 was 18 nM with respect to the cofactor and 91 nM with respect to crotonoyl‐CoA. These inhibitors showed competitive kinetics with cofactor and uncompetitive kinetics with the substrate. Thus, these compounds hold promise for the development of potent antimalarials. © 2011 IUBMB IUBMB Life, 63(12): 1101–1110, 2011