Carbonic anhydrase inhibitors. Inhibition of the prokariotic beta and gamma-class enzymes from Archaea with sulfonamides.
Article Details
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Zimmerman S, Innocenti A, Casini A, Ferry JG, Scozzafava A, Supuran CT
Carbonic anhydrase inhibitors. Inhibition of the prokariotic beta and gamma-class enzymes from Archaea with sulfonamides.
Bioorg Med Chem Lett. 2004 Dec 20;14(24):6001-6.
- PubMed ID
- 15546717 [ View in PubMed]
- Abstract
A detailed inhibition study of carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the beta- and gamma-families from Archaea with sulfonamides has been performed. Compounds included in this study were the clinically used sulfonamide CA inhibitors, such as acetazolamide, methazolamide, ethoxzolamide, topiramate, valdecoxib, celecoxib, dorzolamide, sulfanilamide, dichlorophanamide, as well as sulfanilamide analogs, halogenated sulfanilamides, and some 1,3-benzenedisulfonamide derivatives. The two gamma-CAs from Methanosarcina thermophila (Zn-Cam and Co-Cam) showed very different inhibitory properties with these compounds, as compared to the alpha-CA isozymes hCA I, II, and IX, and the beta-CA from Methanobacterium thermoautotrophicum (Cab). The best Zn-Cam inhibitors were sulfamic acid and acetazolamide, with inhibition constants in the range of 63-96 nM, whereas other investigated aromatic/heterocylic sulfonamides showed a rather levelled behavior, with KIs in the range of 0.12-1.70 microM. The best Co-Cam inhibitors were topiramate and p-aminoethyl-benzenesulfonamide, with KIs in the range of 0.12-0.13 microM, whereas the worst one was homosulfanilamide (KI of 8.50 microM). In the case of Cab, the inhibitory power of these compounds varied to a much larger extent, with sulfamic acid and sulfamide showing millimolar affinities (KIs in the range of 44-103 mM), whereas the best inhibitor was ethoxzolamide, with a KI of 5.35 microM. Most of these sulfonamides showed inhibition constants in the range of 12-100 microM against Cab. Thus, the three CA families investigated up to now possess a very diverse affinity for sulfonamides, the inhibitors with important medicinal, and environmental applications.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) 4-(2-AMINOETHYL)BENZENESULFONAMIDE Carbonic anhydrase 2 Ki (nM) 160000 N/A N/A Details Acetazolamide Carbonic anhydrase 1 Ki (nM) 250 N/A N/A Details Acetazolamide Carbonic anhydrase 2 Ki (nM) 12000 N/A N/A Details Celecoxib Carbonic anhydrase 2 Ki (nM) 21000 N/A N/A Details Diclofenamide Carbonic anhydrase 1 Ki (nM) 1200 N/A N/A Details Diclofenamide Carbonic anhydrase 2 Ki (nM) 38000 N/A N/A Details Dorzolamide Carbonic anhydrase 1 Ki (nM) 50000000 N/A N/A Details Dorzolamide Carbonic anhydrase 2 Ki (nM) 9000 N/A N/A Details Ethoxzolamide Carbonic anhydrase 1 Ki (nM) 20 N/A N/A Details Ethoxzolamide Carbonic anhydrase 2 Ki (nM) 8000 N/A N/A Details Topiramate Carbonic anhydrase 1 Ki (nM) 250 N/A N/A Details Topiramate Carbonic anhydrase 2 Ki (nM) 5000 N/A N/A Details Valdecoxib Carbonic anhydrase 2 Ki (nM) 43000 N/A N/A Details