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Carbonic anhydrase inhibitors. Inhibition of isoforms I, II, IV, VA, VII, IX, and XIV with sulfonamides incorporating fructopyranose-thioureido tails.
Bioorg Med Chem Lett. 2007 May 15; 17(10):2685-91.BM

Abstract

A series of aromatic/heterocyclic sulfonamides incorporating 2,3:4,5-bis-O-(isopropylidene)-beta-d-fructopyranosyl-thioureido moieties has been synthesized and assayed for the inhibition of seven human isoforms of the zinc enzyme carbonic anhydrase (hCA, EC 4.2.1.1). The new derivatives behaved as weak hCA I inhibitors (K(I)s of 9.4 -13.3microM), were efficient hCA II inhibitors (K(I)s of 6-750nM), and slightly inhibited isoforms hCA IV and hCA VA. Only the sulfanilamide derivative showed efficient and selective inhibition of hCA IV (K(I) of 10nM). These derivatives also showed excellent hCA VII inhibitory activity (K(I)s of 10-79nM), being less efficient as inhibitors of the transmembrane isoforms hCA IX (K(I)s of 10-4500nM) and hCA XIV (K(I)s of 21-3500nM). Two of the new compounds showed anticonvulsant action in a maximal electroshock seizure test in mice, with the fluorosulfanilamide derivative being a more efficient anticonvulsant than the antiepileptic drug topiramate.

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Authors+Show Affiliations

Winum JY
Institut des Biomolécules Max Mousseron (IBMM) UMR 5247 CNRS-UM1-UM2 Bâtiment de Recherche Max Mousseron, Ecole Nationale Supérieure de Chimie de Montpellier, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex, France.
Thiry A
No affiliation info available
Cheikh KE
No affiliation info available
Dogné JM
No affiliation info available
Montero JL
No affiliation info available
Vullo D
No affiliation info available
Scozzafava A
No affiliation info available
Masereel B
No affiliation info available
Supuran CT
No affiliation info available

MeSH

AcetazolamideCarbonic Anhydrase ICarbonic Anhydrase IICarbonic Anhydrase InhibitorsHumansIsoenzymesStructure-Activity RelationshipSulfonamides

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17376683

Citation

Winum, Jean-Yves, et al. "Carbonic Anhydrase Inhibitors. Inhibition of Isoforms I, II, IV, VA, VII, IX, and XIV With Sulfonamides Incorporating Fructopyranose-thioureido Tails." Bioorganic & Medicinal Chemistry Letters, vol. 17, no. 10, 2007, pp. 2685-91.
Winum JY, Thiry A, Cheikh KE, et al. Carbonic anhydrase inhibitors. Inhibition of isoforms I, II, IV, VA, VII, IX, and XIV with sulfonamides incorporating fructopyranose-thioureido tails. Bioorg Med Chem Lett. 2007;17(10):2685-91.
Winum, J. Y., Thiry, A., Cheikh, K. E., Dogné, J. M., Montero, J. L., Vullo, D., Scozzafava, A., Masereel, B., & Supuran, C. T. (2007). Carbonic anhydrase inhibitors. Inhibition of isoforms I, II, IV, VA, VII, IX, and XIV with sulfonamides incorporating fructopyranose-thioureido tails. Bioorganic & Medicinal Chemistry Letters, 17(10), 2685-91.
Winum JY, et al. Carbonic Anhydrase Inhibitors. Inhibition of Isoforms I, II, IV, VA, VII, IX, and XIV With Sulfonamides Incorporating Fructopyranose-thioureido Tails. Bioorg Med Chem Lett. 2007 May 15;17(10):2685-91. PubMed PMID: 17376683.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Carbonic anhydrase inhibitors. Inhibition of isoforms I, II, IV, VA, VII, IX, and XIV with sulfonamides incorporating fructopyranose-thioureido tails. AU - Winum,Jean-Yves, AU - Thiry,Anne, AU - Cheikh,Khaled El, AU - Dogné,Jean-Michel, AU - Montero,Jean-Louis, AU - Vullo,Daniela, AU - Scozzafava,Andrea, AU - Masereel,Bernard, AU - Supuran,Claudiu T, Y1 - 2007/03/12/ PY - 2007/01/29/received PY - 2007/03/02/revised PY - 2007/03/03/accepted PY - 2007/3/23/pubmed PY - 2007/7/31/medline PY - 2007/3/23/entrez SP - 2685 EP - 91 JF - Bioorganic & medicinal chemistry letters JO - Bioorg Med Chem Lett VL - 17 IS - 10 N2 - A series of aromatic/heterocyclic sulfonamides incorporating 2,3:4,5-bis-O-(isopropylidene)-beta-d-fructopyranosyl-thioureido moieties has been synthesized and assayed for the inhibition of seven human isoforms of the zinc enzyme carbonic anhydrase (hCA, EC 4.2.1.1). The new derivatives behaved as weak hCA I inhibitors (K(I)s of 9.4 -13.3microM), were efficient hCA II inhibitors (K(I)s of 6-750nM), and slightly inhibited isoforms hCA IV and hCA VA. Only the sulfanilamide derivative showed efficient and selective inhibition of hCA IV (K(I) of 10nM). These derivatives also showed excellent hCA VII inhibitory activity (K(I)s of 10-79nM), being less efficient as inhibitors of the transmembrane isoforms hCA IX (K(I)s of 10-4500nM) and hCA XIV (K(I)s of 21-3500nM). Two of the new compounds showed anticonvulsant action in a maximal electroshock seizure test in mice, with the fluorosulfanilamide derivative being a more efficient anticonvulsant than the antiepileptic drug topiramate. SN - 0960-894X UR - https://www.unboundmedicine.com/medline/citation/17376683 L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-894X(07)00302-2 DB - PRIME DP - Unbound Medicine ER -
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