National Institute of Immunology, New Delhi, India.
IUBMB Life. 2011 Dec;63(12):1101-10. doi: 10.1002/iub.553. Epub 2011 Oct 18.
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.
苯并噻吩衍生物，如苯并噻吩磺酰胺、联苯或羧基，已被合成并发现具有广泛的药理学用途。在这里，我们报告了溴代苯并噻吩甲酰胺衍生物作为有效的、缓慢的紧密结合抑制剂，对疟原虫烯酰基载体蛋白（ACP）还原酶（PfENR）具有抑制作用。3-溴-N-（4-氟苄基）-苯并[b]噻吩-2-甲酰胺（化合物 6）是最有效的抑制剂，对纯化的 PfENR 的 IC50 为 115 nM。化合物 6 对辅因子的抑制常数（Ki）为 18 nM，对丙二酰辅酶 A 的 Ki 为 91 nM。这些抑制剂对辅因子表现出竞争性动力学，对底物表现出非竞争性动力学。因此，这些化合物有望开发出有效的抗疟药物。
