Sulfonamide inhibition studies of the 未-carbonic anhydrase from the diatom Thalassiosira weissflogii
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- 作者：Daniela Vullo ; Sonia Del Prete ; Sameh M. Osman ; Viviana De Luca ; Andrea Scozzafava ; Zeid AlOthman ; Claudiu T. Supuran ; Clemente Capasso
- 关键词：Carbonic anhydrase ; 未-Class enzyme ; Sulfonamide ; Enzyme inhibitor ; Thalassiosira weissflogii
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：1 January, 2014
- 年：2014
- 卷：24
- 期：1
- 页码：275-279
- 全文大小：327 K
文摘
The 未-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 未-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 未-class enzyme, with KIs of 4.27-9.20 渭M. The inhibition profile of the 未-CA is very different from that of 伪-, 尾- and 纬-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 未-CA active site.