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Carbonic anhydrase inhibitors: SAR and x-ray crystallographic study for the interaction of sugar sulfamates/sulfamides with Isozymes I, II and IV

Casini, Angela, Antel, J, Abbate, F, Scozzafava, A, David, S, Waldeck, H, Schafer, S and Supuran, C. T. 2003. Carbonic anhydrase inhibitors: SAR and x-ray crystallographic study for the interaction of sugar sulfamates/sulfamides with Isozymes I, II and IV. Biorganic and Medicinal Chemistry Letters 13 (5) , pp. 841-845. 10.1016/S0960-894X(03)00029-5

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Abstract

A series of sugar sulfamate/sulfamide derivatives were prepared and assayed as inhibitors of three carbonic anhydrase (CA) isozymes, hCA I, hCA II and bCA IV. Best inhibitory properties were observed for the clinically used antiepileptic drug topiramate, which is a low nanomolar CA II inhibitor, and possesses good inhibitory properties against the other two isozymes investigated here, similarly with acetazolamide, methazolamide or dichlorophenamide. The X-ray structure of the complex of topiramate with hCA II has been solved and it revealed a very tight association of the inhibitor, with a network of seven strong hydrogen bonds fixing topiramate within the active site, in addition to the Zn(II) coordination through the ionized sulfamate moiety. Structural changes in this series of sugar derivatives led to compounds with diminished CA inhibitory properties as compared to topiramate.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Subjects: Q Science > QD Chemistry
Uncontrolled Keywords: Animals; Binding Sites; Carbonic Anhydrase I; Carbonic Anhydrase II; Carbonic Anhydrase Inhibitors; Carbonic Anhydrase IV; Cattle; Crystallography, X-Ray; Fructose; Humans; Hydrogen Bonding; Models, Molecular; Structure-Activity Relationship; Sulfonamides; Sulfonic Acids; Zinc
Publisher: Elsevier
ISSN: 0960-894X
Last Modified: 04 Jun 2017 08:49
URI: http://orca.cf.ac.uk/id/eprint/85550

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