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

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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. doi: 10.1016/j.bmcl.2009.01.038. Epub 2009 Jan 19.

PubMed ID
19186056 [ View in PubMed
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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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Carbonic anhydrase 1P00915Details
Carbonic anhydrase 2P00918Details
Carbonic anhydrase 4P22748Details
Carbonic anhydrase 12O43570Details
Carbonic anhydrase 9Q16790Details
Carbonic anhydrase 3P07451Details
Carbonic anhydrase 5A, mitochondrialP35218Details
Carbonic anhydrase 5B, mitochondrialQ9Y2D0Details
Carbonic anhydrase 6P23280Details
Carbonic anhydrase 7P43166Details
Carbonic anhydrase 14Q9ULX7Details
Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
2-(1,3-thiazol-4-yl)-1H-benzimidazole-5-sulfonamideCarbonic anhydrase 2Ki (nM)72.5N/AN/ADetails
2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamideCarbonic anhydrase 2Ki (nM)7.2N/AN/ADetails
AcetazolamideCarbonic anhydrase 1Ki (nM)250N/AN/ADetails
AcetazolamideCarbonic anhydrase 12Ki (nM)5.7N/AN/ADetails
AcetazolamideCarbonic anhydrase 14Ki (nM)41N/AN/ADetails
AcetazolamideCarbonic anhydrase 2Ki (nM)12N/AN/ADetails
AcetazolamideCarbonic anhydrase 3Ki (nM)200000N/AN/ADetails
AcetazolamideCarbonic anhydrase 4Ki (nM)74N/AN/ADetails
AcetazolamideCarbonic anhydrase 7Ki (nM)2.5N/AN/ADetails
EthoxzolamideCarbonic anhydrase 1Ki (nM)25N/AN/ADetails
EthoxzolamideCarbonic anhydrase 2Ki (nM)8N/AN/ADetails
EthoxzolamideCarbonic anhydrase 3Ki (nM)1100000N/AN/ADetails
EthoxzolamideCarbonic anhydrase 4Ki (nM)93N/AN/ADetails
EthoxzolamideCarbonic anhydrase 7Ki (nM)0.8N/AN/ADetails