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

Journal of Enzyme Inhibition and Medicinal Chemistry

Sonia Del Prete¹  Clemente Capasso¹  Rosaria Gitto²  Laura De Luca²  Francesca Mancuso²  Claudiu T. Supuran³  Daniela Vullo³ 

[1] Department of Biology, Agriculture and Food Sciences, Institute of Biosciences and Bioresources- CNR, Napoli, Italy;Department of Chemical, Biological, Pharmaceutical and Environmental Sciences (CHIBIOFARAM), University of Messina, Messina, Italy;NUROFARBA Department, University of Florence, Sesto Fiorentino, Ital;

关键词: Carbonic anhydrase inhibitors (CAIs);    benzenesulfonamides;    Vibrio cholera;    molecular docking;   

DOI  :  10.1080/14756366.2019.1618292

来源: publisher

【 摘 要 】

A series of sixteen benzenesulfonamide derivatives has been synthesised and tested as inhibitors of Vibrio cholerae carbonic anhydrase (CA) enzymes, belonging to α-CA, β-CA, and γ-CA classes (VchCAα, VchCAβ, and VchCAγ). 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 VchCAα at nanomolar concentration. The VchCAβ activity was lower to respect inhibitory efficacy toward VchCAα, whereas, these benzenesulfonamide derivatives failed to inhibit VchCAγ. Interestingly, compound 7e combined the best activity toward VchCAα and VchCAβ. 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 VchCAβ.

【 授权许可】

CC BY