Design, synthesis and biological evaluation of some novel benzenesulfonamide derivatives as potential carbonic anhydrase inhibitors

Abstract

New series of benzenesulfonamide and benzoic acid derivatives were designed and synthesized using tail/dual tail approach to improve potency and selectivity as carbonic anhydrase inhibitors. The synthesized compounds evaluated as CAIs against isoforms hCA I, II, IV and IX with AAZ as standard inhibitor. The benzenesulfonamide derivatives Va-h, IXa-d, XIIIa-c, XIVa and XVIa-c showed moderate to potent inhibitory activity with selectivity toward isoform hCA II, especially, compound XIIIa with (Ki= 7.6 nM), while the benzoic acid analogues XIIId-f, XIVb and XVId-f didn’t show any activity except compounds XIIId,e and XVIf that showed weak activity. Additionally, molecular docking was performed for compounds IXa, Va, Ve, XIIIa, XIVa and XVIa on isoform hCA I, II to illustrate the possible interaction with the active site to justify the inhibitory activity.