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

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(I)s of 6.4-9.5 nm) and also inhibited effectively isozymes CA I, II, IV-VII, and XII, with KIs 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. (C) 2009 Elsevier Ltd. All rights reserved.