Carbonic anhydrase inhibitors: crystallographic and solution binding studies for the interaction of a boron-containing aromatic sulfamide with mammalian isoforms I-XV.
Article Details
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Di Fiore A, Monti SM, Innocenti A, Winum JY, De Simone G, Supuran CT
Carbonic anhydrase inhibitors: crystallographic and solution binding studies for the interaction of a boron-containing aromatic sulfamide with mammalian isoforms I-XV.
Bioorg Med Chem Lett. 2010 Jun 15;20(12):3601-5. doi: 10.1016/j.bmcl.2010.04.114. Epub 2010 Apr 28.
- PubMed ID
- 20472429 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Acetazolamide Carbonic anhydrase 1 Ki (nM) 250 N/A N/A Details Acetazolamide Carbonic anhydrase 12 Ki (nM) 5.7 N/A N/A Details Acetazolamide Carbonic anhydrase 14 Ki (nM) 41 N/A N/A Details Acetazolamide Carbonic anhydrase 2 Ki (nM) 12 N/A N/A Details Acetazolamide Carbonic anhydrase 3 Ki (nM) 200000 N/A N/A Details Acetazolamide Carbonic anhydrase 4 Ki (nM) 74 N/A N/A Details Acetazolamide Carbonic anhydrase 7 Ki (nM) 2.5 N/A N/A Details Ethoxzolamide Carbonic anhydrase 1 Ki (nM) 25 N/A N/A Details Ethoxzolamide Carbonic anhydrase 2 Ki (nM) 8 N/A N/A Details Ethoxzolamide Carbonic anhydrase 3 Ki (nM) 1000000 N/A N/A Details Ethoxzolamide Carbonic anhydrase 4 Ki (nM) 93 N/A N/A Details Ethoxzolamide Carbonic anhydrase 7 Ki (nM) 0.8 N/A N/A Details Topiramate Carbonic anhydrase 1 Ki (nM) 250 N/A N/A Details Topiramate Carbonic anhydrase 2 Ki (nM) 10 N/A N/A Details Topiramate Carbonic anhydrase 3 Ki (nM) 780000 N/A N/A Details Topiramate Carbonic anhydrase 4 Ki (nM) 4900 N/A N/A Details