Facile synthesis of aminobiphenyl sulfonamides via Chan-Lam coupling and their biological evaluation as potent carbonic anhydrase inhibitors.

Inhibition of carbonic anhydrases (EC 4.2.1.1, hCAs) is known to be a potential target for treatment of several disorders like epilepsy, glaucoma, obesity, and cancer. The current research focuses on the synthesis of a series of 4'-amino-[1,1'-biphenyl]-4-sulfonamide derivatives (9a-e) through cross-coupling reactions in the presence of Cu(OAc) catalyst. The structural elucidation of synthesized derivatives was carried out throughH NMR, andC NMR. These sulphonamide derivatives were screened for inhibitory potential towards various isozymes of carbonic anhydrases including hCA-II, hCA-IX, and hCA-XII. Enzyme inhibition assay exhibited that synthesized derivatives with IC ± SEM, 9e (0.38 ± 0.03µM), 9d (0.21 ± 0.03 µM) and 9b (0.69 ± 0.15 µM) had remarkable inhibition potency against hCA-II, hCA-IX and hCA-XII respectively. It was noted that 9d exhibited 8-fold more inhibitor potential as compared to standard inhibitor acetazolamide. For the most potent inhibitors, enzyme kinetic analysis was also carried out to find inhibition mode. Furthermore, the drug-ability of synthesized compounds was evaluated through SwissADME tools, and found that all the newly prepared derivatives successfully satisfied the drug-ability criteria. Molecular docking studies were conducted to identify the types of interactions between the synthesized ligands and the target proteins.