Coumarin-Containing Aromatic Sulfonamides With Carbonic Anhydrase Inhibitory Properties Against Human and Fungal Isoforms

The vital process of CO2 hydration in all living things is catalyzed by carbonic anhydrases (CAs, EC 4.2.1.1), which are actively involved in the control of numerous pathological and physiological situations. A number of coumarin-based sulfonamides (18) were examined as potential CA inhibitors. Their inhibitory activity was assessed against the cytosolic human isoforms hCA I, hCA II, and the transmembrane hCA IX as well as against three fungal CAs: Malassezia globosa (MgCA), Malassezia pachydermatis (MpaCA), and Malassezia restricta (MreCA). Additionally, the binding mechanism of this family of chemicals within the active site of hCA IX was investigated using computational approaches. Compounds showed interesting inhibitory activity mainly against two fungal strains, Malassezia globosa (MgCA) and Malassezia pachydermatis (MpaCA), exceeding in the first case the activity of the reference drug, and in the second, 16 out of 18 showed Ki values lower than acetozolamide. Furthermore, four compounds were more potent against hCA I than AAZ and two against hCA II. Docking studies were used to investigate the binding mode of the most active compounds against human CA isoforms.