The extremo-¦Á-carbonic anhydrase from the thermophilic bacterium Sulfurihydrogenibium azorense is highly inhibited by sulfonamides
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- 作者：Daniela Vullo ; Viviana De Luca ; Andrea Scozzafava ; Vincenzo Carginale ; Mos¨¨ Rossi ; Claudiu T. Supuran ; Clemente Capasso
- 关键词：Carbonic anhydrase ; Anion ; ¦Á-Class enzyme ; Inhibitor ; Sulfurihydrogenibium azorense ; Thermophilic bacteria
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2013
- 出版时间：1 August, 2013
- 年：2013
- 卷：21
- 期：15
- 页码：4521-4525
- 全文大小：507 K
文摘
The ¦Á-carbonic anhydrase (CA, EC 4.2.1.1) from the newly discovered extremophilic bacterium Sulfurihydrogenibium azorense (SazCA) is the most effective CA known to date. Here we investigated the inhibition profile of this enzyme with a series of aromatic and heterocyclic sulfonamides, and one sulfamate. Many clinically used sulfonamides, such as acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, topiramate, celecoxib and sulpiride were low nanomolar/subnanomolar SazCA inhibitors (KIs in the range of 0.9-10.8 nM) whereas simple aromatic derivatives were less effective as SazCA inhibitors. The inhibition profile of SazCA is slightly different from that of the related enzyme from S. yellostonense (SspCA), investigated earlier by our groups.