a Department of Chemical, Biological, Pharmaceutical and Environmental Sciences (CHIBIOFARAM) , University of Messina , Messina , Italy.
b Department of Biology , Agriculture and Food Sciences, Institute of Biosciences and Bioresources- CNR , Napoli , Italy.
J Enzyme Inhib Med Chem. 2019 Dec;34(1):1186-1192. doi: 10.1080/14756366.2019.1618292.
A series of sixteen benzenesulfonamide derivatives has been synthesised and tested as inhibitors of carbonic anhydrase (CA) enzymes, belonging to -CA, -CA, and -CA classes (VchCA, VchCA, and VchCA). The determined values were compared to those of selected human CA isoforms (hCA I and hCA II). Structure-affinity relationship analysis highlighted that all tested compounds proved to be active inhibitors of VchCA at nanomolar concentration. The VchCA activity was lower to respect inhibitory efficacy toward VchCA, whereas, these benzenesulfonamide derivatives failed to inhibit VchCA. Interestingly, compound combined the best activity toward VchCA and VchCA. In order to obtain a model for binding mode of our inhibitors toward bacterial CAs, we carried out docking simulations by using the available crystal structures of VchCA.
已经合成了一系列十六个苯磺酰胺衍生物，并对其作为碳酸酐酶（CA）酶抑制剂的活性进行了测试，这些酶属于 -CA、-CA 和 -CA 类（VchCA、VchCA 和 VchCA）。测定的 值与选定的人源 CA 同工型（hCA I 和 hCA II）进行了比较。结构-亲和力关系分析表明，所有测试的化合物均被证明在纳摩尔浓度下对 VchCA 具有活性抑制作用。VchCA 的活性低于对 VchCA 的抑制效果，而这些苯磺酰胺衍生物未能抑制 VchCA。有趣的是，化合物 对 VchCA 和 VchCA 均具有最佳的活性。为了获得我们的抑制剂与细菌 CA 结合模式的模型，我们使用 VchCA 的现有晶体结构进行了对接模拟。
