A series of sulfonamides incorporating cyclic imide moieties were investigated as inhibitors of several human α-carbonic anhydrase (hCA, EC 4.2.1.1) isoforms. Several carboxylic acids possessing the same scaffolds as the sulfonamides were also included in the study, since the sulfonamidate and the carboxylate are among the frequently used zinc-binding groups (ZBGs) for obtaining zinc enzymes inhibitors. The cytosolic isoform hCA I was moderately inhibited by most of the 30 investigated derivatives; many low nanomolar hCA II inhibitors were detected, whereas some of these compounds were low nanomolar/subnanomolar inhibitors of the transmembrane, tumor-associated isoforms hCA IX and XII. In this series of compounds the SO(2)NH(-) and the COO(-) ZBGs showed similar efficacy for obtaining potent inhibitors, although some carboxylates had isoform-selective inhibition profiles for the transmembrane CAs.
Keywords: Carbonic anhydrase; Carboxylic acid; Inhibitor; Isoform-selective inhibitor; Sulfonamide; Zinc-binding groups.
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