p-Aminobenzene-Sulfonamide Derivatives of Substituted Pyrimidines as Human Carbonic Anhydrase Inhibitors.

The essential reaction of CO2 hydration, fundamental to all living organisms, is facilitated by the enzyme carbonic anhydrase (CA, EC 4.2.1.1). This enzyme plays a crucial role in regulating various physiological and pathological processes. A series of heterocyclic benzenesulfonamide derivatives (19 compounds) were evaluated as possible inhibitors of human CAs. Their inhibitory properties were tested against several isoforms such as the cytosolic hCA I and hCA II, as well as the transmembrane isoforms hCA IV, hCA IX and hCA XII. The tested molecules demonstrated notable inhibitory potential, particularly toward hCA II and hCA IV, where five and four compounds, respectively, exhibited greater potency than the reference inhibitor, acetazolamide. Molecular docking simulations were further performed to elucidate the binding interactions of the most active compounds with the human CA II, IV IX and XII isoforms.