Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Istanbul University, Beyazit, 34116 Istanbul, Turkey.
Neurofarba Department, Section of Pharmaceutical and Nutriceutical Sciences, Università degli Studi di Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino (Florence), Italy.
Int J Mol Sci. 2020 Apr 29;21(9):3131. doi: 10.3390/ijms21093131.
Due to the increasing resistance of currently used antimicrobial drugs, there is an urgent problem for the treatment of cholera disease, selective inhibition of the α-class carbonic anhydrases (CA, EC 4.2.1.1) from the pathogenic bacterium (VcCA) presents an alternative therapeutic target. In this study, a series of hydrazone derivatives, carrying the 2-(hydrazinocarbonyl)-3-phenyl-1-indole-5-sulfonamide scaffold, have been evaluated as inhibitors of the VcCA with molecular modeling studies. The results suggest that these compounds may bind to the active site of VcCA. To verify this, VcCA enzyme inhibition studies were performed and as predicted most of the tested compounds displayed potent inhibitory activities against VcCA with three compounds showing values lower than 30 nM. In addition, all these compounds showed selectivity for VcCA and the off-targets hCA I and II.
由于目前使用的抗菌药物的耐药性不断增加，治疗霍乱病的方法存在迫切的问题，因此选择性抑制致病细菌（VcCA）的α级碳酸酐酶（CA，EC 4.2.1.1）是一个替代的治疗靶点。在这项研究中，一系列带有 2-（肼羰基）-3-苯基-1-吲哚-5-磺酰胺支架的腙衍生物被评估为 VcCA 的抑制剂，并进行了分子建模研究。结果表明，这些化合物可能与 VcCA 的活性位点结合。为了验证这一点，进行了 VcCA 酶抑制研究，正如预测的那样，大多数测试化合物对 VcCA 表现出很强的抑制活性，其中三种化合物的 值低于 30 nM。此外，所有这些化合物对 VcCA 具有选择性，对靶标 hCA I 和 II 没有活性。
