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

Bioorg Med Chem Lett. 2009 Mar 1;19(5):1371-5. doi: 10.1016/j.bmcl.2009.01.038.

Letizia Crocetti ¹, Alfonso Maresca, Claudia Temperini, Rebecca A Hall, Andrea Scozzafava, Fritz A Mühlschlegel, Claudiu T Supuran

Affiliations

Affiliation

1 Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.

PMID: 19186056 DOI: 10.1016/j.bmcl.2009.01.038

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(I)s of 6.4-9.5nm) and also inhibited effectively isozymes CA I, II, IV-VII, and XII, with K(I)s in the range of 17.8-73.2nM. The high resolution X-ray crystal structure of its adduct with isozyme II evidenced the structural elements responsible for this potent inhibitory activity.

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