Benzothiophene Carboxamide Derivatives as Inhibitors of Plasmodium falciparum Enoyl-ACP Reductase

Banerjee, Tanushree and Sharma, Shailendra Kumar and Kapoor, Neha and Dwivedi, Vishnu and Surolia, Namita and Surolia, Avadhesha (2011) Benzothiophene Carboxamide Derivatives as Inhibitors of Plasmodium falciparum Enoyl-ACP Reductase. In: IUBMB Life, 63 (12). pp. 1101-1110.

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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 IC(50) of 115 nM for purified PfENR. The inhibition constant (K(i)) 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. (C) 2011 IUBMB IUBMB Life, 63(12): 1101-1110, 2011

Item Type:	Journal Article
Publication:	IUBMB Life
Publisher:	John Wiley and Sons
Additional Information:	Copyright of this article belongs to John Wiley and Sons.
Keywords:	bromo-benzothiophene;benzothiophene carboxamide; antimalarials;Plasmodium
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	10 Jan 2012 12:29
Last Modified:	10 Jan 2012 12:29
URI:	http://eprints.iisc.ac.in/id/eprint/43109

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