Carbonic anhydrase inhibitors. Inhibition of the prokariotic beta and gamma-class enzymes from Archaea with sulfonamides.

Article Details


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

A detailed inhibition study of carbonic anhydrases (CAs, EC 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
DrugTargetPropertyMeasurementpHTemperature (°C)
4-(2-AMINOETHYL)BENZENESULFONAMIDECarbonic anhydrase 2Ki (nM)160000N/AN/ADetails
AcetazolamideCarbonic anhydrase 1Ki (nM)250N/AN/ADetails
AcetazolamideCarbonic anhydrase 2Ki (nM)12000N/AN/ADetails
CelecoxibCarbonic anhydrase 2Ki (nM)21000N/AN/ADetails
DiclofenamideCarbonic anhydrase 1Ki (nM)1200N/AN/ADetails
DiclofenamideCarbonic anhydrase 2Ki (nM)38000N/AN/ADetails
DorzolamideCarbonic anhydrase 1Ki (nM)50000000N/AN/ADetails
DorzolamideCarbonic anhydrase 2Ki (nM)9000N/AN/ADetails
EthoxzolamideCarbonic anhydrase 1Ki (nM)20N/AN/ADetails
EthoxzolamideCarbonic anhydrase 2Ki (nM)8000N/AN/ADetails
TopiramateCarbonic anhydrase 1Ki (nM)250N/AN/ADetails
TopiramateCarbonic anhydrase 2Ki (nM)5000N/AN/ADetails
ValdecoxibCarbonic anhydrase 2Ki (nM)43000N/AN/ADetails