title: Benzothiophene carboxamide derivatives as inhibitors of Plasmodium falciparum enoyl-ACP reductase.
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.
authors: National Institute of Immunology, New Delhi, India.
authors: Tanushree
authors: T
authors: Banerjee
authors: Shailendra Kumar
authors: SK
authors: Sharma
authors: Neha
authors: N
authors: Kapoor
authors: Vishnu
authors: V
authors: Dwivedi
authors: Namita
authors: N
authors: Surolia
authors: Avadhesha
authors: A
authors: Surolia
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry*; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology / Q000473:pathology; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism / Q000472:pathogenicity*; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D000962:Antimalarials; D004791:Enzyme Inhibitors; D013876:Thiophenes; C088015:benzothiophene; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)