Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with the antipsychotic drug sulpiride

Abbate, F, Coetzee, A, Casini, Angela ORCID: https://orcid.org/0000-0003-1599-9542, Ciattini, S, Scozzafava, A and Supuran, CT 2004. Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with the antipsychotic drug sulpiride. Bioorganic and Medicinal Chemistry Letters 14 (2) , pp. 337-341. 10.1016/j.bmcl.2003.11.014

Full text not available from this repository.

Abstract

The X-ray crystal structure for the adduct of human carbonic anhydrase (hCA) II with sulpiride, a sulfonamide derivative clinically used as antipsychotic drug, has been resolved at a resolution of 1.6 Å. This compound is an effective inhibitor of the physiologically most relevant isozyme hCA II (Ki of 40 nM), being only a moderate or moderate-weak inhibitor of the cytosolic isozyme hCA I (Ki of 1200 nM) and the membrane-bound isozyme hCA IV (Ki of 620 nM). Sulpiride shows CA inhibitory properties of the same magnitude as dichlorophenamide, a clinically used antiglaucoma sulfonamide, or valdecoxib, a COX-2 selective inhibitor recently shown to inhibit CA. The binding of sulpiride to the hCA II active site is similar to that of other sulfonamide inhibitors, considering the interactions of the sulfonamide zinc anchoring group, but differs considerably when the organic scaffold of the molecule is analyzed. Indeed, one unprecedented hydrogen bond involving the imino moiety of the carboxamido group of sulpiride and a water molecule was observed, together with a unique stacking interaction of the N-methyl-pyrrolidine ring of the inhibitor and the aromatic ring of Phe 131 of the enzyme active site, which has been observed only recently in another CA–sulfonamide complex.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Subjects: Q Science > QD Chemistry
R Medicine > RM Therapeutics. Pharmacology
Publisher: Elsevier
ISSN: 0960-894X
Last Modified: 31 Oct 2022 10:38
URI: https://orca.cardiff.ac.uk/id/eprint/85538

Citation Data

Cited 64 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item