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

Bioorganic & Medicinal Chemistry Letters
2010.0

Abstract

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.

DOI： 10.1016/j.bmcl.2010.04.114

Knowledge Graph

Similar Paper

Carbonic anhydrase inhibitors: Crystallographic and solution binding studies for the interaction of a boron-containing aromatic sulfamide with mammalian isoforms I–XV
Bioorganic & Medicinal Chemistry Letters 2010.0
Coumarinyl-substituted sulfonamides strongly inhibit several human carbonic anhydrase isoforms: solution and crystallographic investigations
Bioorganic & Medicinal Chemistry 2010.0
Carbonic anhydrase inhibitors. Interaction of 2-N,N-dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide with 12 mammalian isoforms: Kinetic and X-ray crystallographic studies
Bioorganic & Medicinal Chemistry Letters 2008.0
Development of Potent Carbonic Anhydrase Inhibitors Incorporating Both Sulfonamide and Sulfamide Groups
Journal of Medicinal Chemistry 2012.0
Carbonic anhydrase inhibitors: Inhibition of human, bacterial, and archaeal isozymes with benzene-1,3-disulfonamides—Solution and crystallographic studies
Bioorganic & Medicinal Chemistry Letters 2007.0
Carbonic anhydrase inhibitors. Inhibition of cytosolic isoforms I and II, and extracellular isoforms IV, IX, and XII with sulfamides incorporating sugar moieties
Bioorganic & Medicinal Chemistry Letters 2007.0
Carbonic anhydrase inhibitors. The X-ray crystal structure of human isoform II in adduct with an adamantyl analogue of acetazolamide resides in a less utilized binding pocket than most hydrophobic inhibitors
Bioorganic & Medicinal Chemistry Letters 2010.0
Carbonic Anhydrase Inhibitors. Comparison of Aliphatic Sulfamate/Bis-sulfamate Adducts with Isozymes II and IX as a Platform for Designing Tight-Binding, More Isoform-Selective Inhibitors
Journal of Medicinal Chemistry 2009.0
Conformational variability of different sulfonamide inhibitors with thienyl-acetamido moieties attributes to differential binding in the active site of cytosolic human carbonic anhydrase isoforms
Bioorganic & Medicinal Chemistry 2011.0
Synthesis, Structure–Activity Relationship Studies, and X-ray Crystallographic Analysis of Arylsulfonamides as Potent Carbonic Anhydrase Inhibitors
Journal of Medicinal Chemistry 2012.0