Benzamide-4-Sulfonamides Are Effective Human Carbonic Anhydrase I, II, VII, and IX Inhibitors.

A series of benzamides incorporating 4-sulfamoyl moieties were obtained by reacting 4-sulfamoyl benzoic acid with primary and secondary amines and amino acids. These sulfonamides were investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The human (h) isoforms hCA II, VII, and IX were inhibited in the low nanomolar or subnanomolar ranges, whereas hCA I was slightly less sensitive to inhibition (KI s of 5.3⁻334 nM). The β- and γ-class CAs from pathogenic bacteria and fungi, such as Vibrio cholerae and Malassezia globosa , were inhibited in the micromolar range by the sulfonamides reported in the paper. The benzamide-4-sulfonamides are a promising class of highly effective CA inhibitors.