A thiabendazole sulfonamide shows potent inhibitory activity against mammalian and nematode α-carbonic anhydrases

Abstract

A sulfonamide derivative of the antihelmintic drug thiabendazole was prepared and investigated for inhibition of the zinc enzyme carbonic anhydrase CA (EC 4.2.1.1). Mammalian isoforms CA I–XIV and the nematode enzyme of Caenorhabditis elegans CAH-4b were included in this study. Thiabendazole-5-sulfonamide was a very effective inhibitor of CAH-4b and CA IX ( K Is of 6.4–9.5 nm) and also inhibited effectively isozymes CA I, II, IV–VII, and XII, with K Is in the range of 17.8–73.2 nM. The high resolution X-ray crystal structure of its adduct with isozyme II evidenced the structural elements responsible for this potent inhibitory activity.