Carbonic anhydrase inhibitors: Crystallographic and solution binding studies for the interaction of a boron-containing aromatic sulfamide with mammalian isoforms I–XV

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• 作者：Anna Di Fiore ; Simona Maria Monti ; Alessio Innocenti ; Jean-Yves Winum ; Giuseppina De Simone ; Claudiu T. Supuran
• 关键词：Carbonic anhydrase ; Sulfamide ; Sulfonamide ; Dioxaborolan ; X-ray crystallography
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2010
• 出版时间：15 June 2010
• 年：2010
• 卷：20
• 期：12
• 页码：3601-3605
• 全文大小：780 K

文摘

We investigated the inhibition of carbonic anhydrase (CA, EC 4.2.1.1) isoforms I–XV with 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylsulfamide and other simple or sugar sulfamides, a class of less investigated CA inhibitors (CAIs). The crystal structure of the adduct of hCA II with the boron-substituted sulfamide shows the organic scaffold of this compound bound in the hydrophilic half of the active site where it makes a large number of van der Waals contacts with Ile91, Gln92, Val121, Phe131, Leu198, and Thr200. The data here reported provide further insights into sulfamide binding mechanism confirming that this zinc-binding group could be usefully exploited for obtaining new potent and selective CAIs.