Seeking new approach for therapeutic treatment of cholera disease via inhibition of bacterial carbonic anhydrases: experimental and theoretical studies for sixteen benzenesulfonamide derivatives

A series of sixteen benzenesulfonamide derivatives has been synthesised and tested as inhibitors of Vibrio cholerae carbonic anhydrase (CA) enzymes, belonging to alpha-CA, beta-CA, and gamma-CA classes (VchCA alpha, VchCA beta, and VchCA gamma). The determined K-i 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 alpha at nanomolar concentration. The VchCA beta activity was lower to respect inhibitory efficacy toward VchCA alpha, whereas, these benzenesulfonamide derivatives failed to inhibit VchCA gamma. Interestingly, compound 7e combined the best activity toward VchCA alpha and VchCA beta. 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 beta.[GRAPHICS].