Carbonic anhydrase inhibitors. Inhibition of the membrane-bound human and bovine isozymes IV with sulfonamides.

Article Details


Innocenti A, Firnges MA, Antel J, Wurl M, Scozzafava A, Supuran CT

Carbonic anhydrase inhibitors. Inhibition of the membrane-bound human and bovine isozymes IV with sulfonamides.

Bioorg Med Chem Lett. 2005 Feb 15;15(4):1149-54.

PubMed ID
15686931 [ View in PubMed

An inhibition study of the human and bovine membrane-associated isozymes of carbonic anhydrase (CA, EC, hCA IV and bCA IV, with a series of sulfonamides and sulfamates, some of which are widely clinically used, such as acetazolamide, methazolamide, ethoxzolamide, topiramate, dorzolamide, dichlorophenamide, celecoxib, and valdecoxib among others, is reported. In contrast to bCA IV, which is generally strongly inhibited by most of these derivatives, hCA IV has a rather different inhibition profile. Several of these compounds such as acetazolamide, ethoxzolamide, and bromosulfanilamide are potent hCA IV inhibitors (K(i)'s of 74-93 nM), others, such as celecoxib and some halogenated sulfanilamides are medium potency inhibitors (K(i)'s of 450-880 nM) whereas most of them are weak hCA IV inhibitors (methazolamide: 6.2 microM; dorzolamide 8.5 microM; topiramate 4.9 microM; dichlorophenamide: 15.3 microM). The hCA IV/bCA IV inhibition ratios for all the investigated compounds ranged between 1.05 (for acetazolamide) and 198.37 (for dorzolamide). Based on these results, we doubt that hCA IV is indeed one of the main contributors to the intraocular pressure (IOP) lowering effects of sulfonamide CA inhibitors, in addition to hCA II, as hypothesized earlier by Maren et al. (Mol. Pharmacol.1993, 44, 901-906). Indeed, both the very good hCA IV inhibitors (acetazolamide and ethoxzolamide) as well as the quite weak hCA IV inhibitors (methazolamide, dorzolamide, or dichlorophanamide) are effective in lowering IOP when administered either systemically or topically. The membrane-associated isozyme which probably is critical for aqueous humor secretion is hCA XII and not hCA IV.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
4-(2-AMINOETHYL)BENZENESULFONAMIDECarbonic anhydrase 2Ki (nM)160N/AN/ADetails
AcetazolamideCarbonic anhydrase 1Ki (nM)250N/AN/ADetails
AcetazolamideCarbonic anhydrase 2Ki (nM)12N/AN/ADetails
AcetazolamideCarbonic anhydrase 4Ki (nM)74N/AN/ADetails
CelecoxibCarbonic anhydrase 2Ki (nM)21N/AN/ADetails
DiclofenamideCarbonic anhydrase 1Ki (nM)1200N/AN/ADetails
DiclofenamideCarbonic anhydrase 2Ki (nM)38N/AN/ADetails
DiclofenamideCarbonic anhydrase 4Ki (nM)15330N/AN/ADetails
DorzolamideCarbonic anhydrase 1Ki (nM)50000000N/AN/ADetails
DorzolamideCarbonic anhydrase 2Ki (nM)9N/AN/ADetails
DorzolamideCarbonic anhydrase 4Ki (nM)8530N/AN/ADetails
EthoxzolamideCarbonic anhydrase 1Ki (nM)25N/AN/ADetails
EthoxzolamideCarbonic anhydrase 2Ki (nM)8N/AN/ADetails
EthoxzolamideCarbonic anhydrase 4Ki (nM)93N/AN/ADetails
TopiramateCarbonic anhydrase 1Ki (nM)250N/AN/ADetails
TopiramateCarbonic anhydrase 2Ki (nM)5N/AN/ADetails
TopiramateCarbonic anhydrase 4Ki (nM)4900N/AN/ADetails
ValdecoxibCarbonic anhydrase 2Ki (nM)43N/AN/ADetails