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 ?-CA, ?-CA, and ?-CA classes (VchCA?, VchCA?, and VchCA?). The determined Ki 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 7e 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?.