Carbonic anhydrase inhibitors: The X-ray crystal structure of ethoxzolamide complexed to human isoform II reveals the importance of thr200 and gln92 for obtaining tight-binding inhibitors
- 作者：Anna Di Fiore ; Carlo Pedone ; Jochen Antel ; Harald Waldeck ; Andreas Witte ; Michael Wurl ; Andrea Scozzafava ; Claudiu T. Supuran ; Giuseppina De Simone
- 关键词：Protein crystallography ; Carbonic Anhydrase ; Ethoxzolamide
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2008
- 期刊代码：10_0960894x
- 类别：ch
- 出版时间：15 April 2008
- 卷：18
- 期：8
- 页码：2669-2674
- 文件大小：648 K
摘要
Ethoxzolamide, an almost forgotten inhibitor of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), is the only classical inhibitor whose structure in adduct with any isoform was not reported yet. We report here the inhibition data of this molecule with the 12 catalytically active mammalian isozymes (CA I–CA XIV) and the X-ray crystal structure with the cytosolic, ubiquitous isoform CA II. These data are presumably useful for the design of novel CA inhibitors, targeting various CA isozymes, considering that ethoxzolamide was already the lead molecule to obtain the second generation inhibitors, dorzolamide and brinzolamide, clinically used antiglaucoma agents with topical action, as well as various other investigational agents.