1. Benzothiophene carboxamide derivatives as inhibitors of Plasmodium falciparum enoyl-ACP reductase.
- Author
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Banerjee T, Sharma SK, Kapoor N, Dwivedi V, Surolia N, and Surolia A
- Subjects
- Antimalarials chemical synthesis, Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) chemistry, Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) isolation & purification, Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) metabolism, Enzyme Inhibitors chemical synthesis, Humans, Inhibitory Concentration 50, Malaria, Falciparum drug therapy, Malaria, Falciparum parasitology, Malaria, Falciparum pathology, Molecular Structure, Plasmodium falciparum drug effects, Plasmodium falciparum metabolism, Antimalarials chemistry, Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) antagonists & inhibitors, Enzyme Inhibitors chemistry, Plasmodium falciparum enzymology, Plasmodium falciparum pathogenicity, Thiophenes chemical synthesis, Thiophenes chemistry
- 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., (Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.)
- Published
- 2011
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