| 19186056 |
Crocetti L, Maresca A, Temperini C, Hall RA, Scozzafava A, Muhlschlegel FA, Supuran CT: 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. Epub 2009 Jan 19.
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. |
163(2,2,2,3) |