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Sulfonamide inhibition studies of the δ-carbonic anhydrase from the diatom Thalassiosira weissflogii

Research Area: Uncategorized Year: 2014
Type of Publication: Article
Authors:
Journal: Bioorganic and Medicinal Chemistry Letters Volume: 24
Number: 1 Pages: 275-279
Note:
cited By (since 1996)1
Abstract:
The δ-carbonic anhydrase (CA, EC 4.2.1.1) TweCA from the marine diatom Thalassiosira weissflogii has recently been cloned, purified and its activity/inhibition with anions investigated. Here we report the first sulfonamide/sulfamate inhibition study of a δ-class CA. Among the 40 such compounds investigated so far, 3-bromosulfanilamide, acetazolamide, ethoxzolamide, dorzolamide and brinzolamide were the most effective TweCA inhibitors detected, with KIs of 49.6-118 nM. Many simple aromatic sulfonamides as well as dichlorophenamide, benzolamide, topiramate, zonisamide, indisulam and valdecoxib were medium potency inhibitors, (KIs of 375-897 nM). Saccharin and hydrochlorothiazide were ineffective inhibitors of the δ-class enzyme, with KIs of 4.27-9.20 μM. The inhibition profile of the δ-CA is very different from that of α-, β-and γ-CAs from different organisms. Although no X-ray crystal structure of this enzyme is available, we hypothesize that as for other CA classes, the sulfonamides inhibit the enzymatic activity by binding to the Zn(II) ion from the δ-CA active site. © 2013 Elsevier Ltd. All rights reserved.
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