Design, synthesis, and biological evaluation of 3‐benzenesulfonamide‐linked 3‐hydrazinoisatin derivatives as carbonic anhydrase inhibitors

A new series of isatin‐linked benzenesulfonamide derivatives (9a–w) were synthesized using the tail approach and assayed for their inhibitory potency against four different human carbonic anhydrase (hCA) isoforms, hCA I, II, IX, and XII. Most of these synthesized compounds exhibited interesting inhibition potency against isoforms hCA I, IX, and XII in the nanomolar range and by taking the standard drug acetazolamide. The most potent compounds in the case of hCA I were 9c (435.8 nM) and 9s (956.4 nM), for hCA IX, 9a (60.5 nM), 9d (95.6 nM), 9g (92.1 nM), and 9k (75.4 nM), and for hCA XII, 9p (84.5 nM). However, these compounds showed more selectivity toward hCA IX over hCA I, II, and XII. Thus, these compounds can be further developed as potential lead molecules for the development of isoform‐selective hCA IX inhibitors with further structural modifications. A new series of 3‐hydrazinoisatin‐linked 3‐benzenesulfonamide derivatives 9a–w were synthesized and subjected to screening against the human carbonic anhydrase (hCA; EC 4.2.1.1) isoforms hCA I, II, IX, and XII. Most of them displayed good potency and selectivity against the isoform hCA IX.