Investigation of arenesulfonyl-2-imidazolidinones as potent carbonic anhydrase inhibitors

Abstract

A series of arenesulfonyl-2-imidazolidinones incorporating methyl, isopropyl, methoxy, halogen and phenyl moieties were prepared and tested as possible inhibitors of two members of the pH regulatory enzyme family, carbonic anhydrase (CA; EC 4.2.1.1). The inhibitory potencies of the compounds against human isoforms hCA I and hCA II were analyzed by an esterase assay with 4-nitrophenyl acetate as substrate, and the inhibition constants (KI) were calculated. Most compounds investigated here exhibited micromolar inhibition constants against the two isoenzymes. KI values were in the range of 10.2–40.6 μM for hCA I and of 13.1–31.4 μM for hCA II, respectively. Most of the imidazolidinones showed interesting CA inhibitory efficacy, some of them having comparable affinity (for hCA I) as the clinically used sulfonamide acetazolamide (AZA), but their efficacy against hCA II was much lower compared to AZA.