Design and synthesis of some new benzoylthioureido benzenesulfonamide derivatives and their analogues as carbonic anhydrase inhibitors.

The present investigation reports the design and synthesis of three series of benzoylthioureido derivatives bearing either benzenesulfonamide , benzoic acid or ethylbenzoate moieties. The synthesised compounds were screened for their carbonic anhydrase inhibitory activity (CAI) against four isoforms hCA I, II, IX, and XII. Compounds , and exhibited a potent inhibitory activity towards hCAI (s = 58.20, 56.30, 33.00, and 43.00 nM), respectively compared to acetazolamide and SLC-0111 (s = 250.00 and 5080.00 nM). Compounds , and elicited selectivity over h CA II (s = 2.50, 2.10, 56.60,39.60 and 39.00 nM) respectively, relative to and SLC-0111(s = 12.10 and 960.00 nM). Also, compounds , and displayed selectivity against the tumour-associated isoform hCA IX (s = 31.20, 30.00 and 29.00 nM) respectively, compared to and SLC-0111 (s = 25.70 and 45.00 nM). Additionally, compounds and revealed a moderate to superior selectivity towards hCAXII (s = 17.00 and 11.00 nM) relative to and SLC-0111(s = 5.70 and 45.00 nM). Molecular docking and ADME prediction studies were performed on the most active compounds to shed light on their interaction with the hot spots of the active site of CA isoforms, in addition to prediction of their pharmacokinetic and physicochemical properties.