Abstract
A series of heterocyclic benzenesulfonamides incorporating 2-mercapto-3H-quinazolin-4-one tails were prepared by condensation of substituted anthranilic acids with 4-isothiocyanato-benzenesulfonamide. These sulfonamides were investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms hCA I and II (cytosolic isozymes), as well as hCA IX and XII (trans -membrane, tumor-associated enzymes). They acted as medium potency inhibitors of hCA I (K(1)s of 81.0-3084 mu M), being highly effective as hCA II (K(1)s in the range of 0.25-10.8 nM), IX (Kis of 3.7-50.4 nM) and XII (Kis of 0.60-52.9 nM) inhibitors. These compounds should thus be of interest as preclinical candidates in pathologies in which the activity of these enzymes should be inhibited, such as glaucoma (CA II and XII as targets) or some tumors in which the activity of three isoforms (CA II, IX and XII) is dysregulated. (C) 2016 Elsevier Ltd. All rights reserved.