Benzothiophene carboxamide derivatives as inhibitors of Plasmodium falciparum enoyl-ACP reductase |
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Authors: | Banerjee Tanushree Sharma Shailendra Kumar Kapoor Neha Dwivedi Vishnu Surolia Namita Surolia Avadhesha |
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Institution: | National Institute of Immunology, New Delhi, India. |
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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)-benzob]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. |
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