Carbonic anhydrase inhibitors: inhibition of the beta-class enzyme from the yeast Saccharomyces cerevisiae with sulfonamides and sulfamates.

Article Details


Isik S, Kockar F, Aydin M, Arslan O, Guler OO, Innocenti A, Scozzafava A, Supuran CT

Carbonic anhydrase inhibitors: inhibition of the beta-class enzyme from the yeast Saccharomyces cerevisiae with sulfonamides and sulfamates.

Bioorg Med Chem. 2009 Feb 1;17(3):1158-63. doi: 10.1016/j.bmc.2008.12.035. Epub 2008 Dec 24.

PubMed ID
19124253 [ View in PubMed

The protein encoded by the Nce103 gene of Saccharomyces cerevisiae, a beta-carbonic anhydrase (CA, EC designated as scCA, has been cloned, purified, characterized kinetically and investigated for its inhibition with a series of sulfonamides and one sulfamate. The enzyme showed high CO(2) hydrase activity, with a k(cat) of 9.4x10(5)s(-1), and k(cat)/K(M) of 9.8x10(7)M(-1)s(-1). Simple benzenesulfonamides substituted in 2-, 4- and 3,4-positions of the benzene ring with amino, alkyl, halogeno and hydroxyalkyl moieties were weak scCA inhibitors with K(I)s in the range of 0.976-18.45 microM. Better inhibition (K(I)s in the range of 154-654 nM) was observed for benzenesulfonamides incorporating aminoalkyl/carboxyalkyl moieties or halogenosulfanilamides; benzene-1,3-disulfonamides; simple heterocyclic sulfonamides and sulfanilyl-sulfonamides. The clinically used sulfonamides/sulfamate (acetazolamide, ethoxzolamide, methazolamide, dorzolamide, topiramate, celecoxib, etc.) generally showed effective scCA inhibitory activity, with K(I)s in the range of 82.6-133 nM. The best inhibitor (K(I) of 15.1 nM) was 4-(2-amino-pyrimidin-4-yl)-benzenesulfonamide. These inhibitors may be useful to better understand the physiological role of beta-CAs in yeast and some pathogenic fungi which encode orthologues of the yeast enzyme and eventually for designing novel antifungal therapies.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
3-[4-(AMINOSULFONYL)PHENYL]PROPANOIC ACIDCarbonic anhydrase 1Ki (nM)6690N/AN/ADetails
3-[4-(AMINOSULFONYL)PHENYL]PROPANOIC ACIDCarbonic anhydrase 2Ki (nM)495N/AN/ADetails
4-(2-AMINOETHYL)BENZENESULFONAMIDECarbonic anhydrase 2Ki (nM)160N/AN/ADetails
5-(2-chlorophenyl)-1,3,4-thiadiazole-2-sulfonamideCarbonic anhydrase 2Ki (nM)12N/AN/ADetails
5-[(phenylsulfonyl)amino]-1,3,4-thiadiazole-2-sulfonamideCarbonic anhydrase 2Ki (nM)9N/AN/ADetails
AcetazolamideCarbonic anhydrase 1Ki (nM)250N/AN/ADetails
AcetazolamideCarbonic anhydrase 2Ki (nM)12N/AN/ADetails
BrinzolamideCarbonic anhydrase 1Ki (nM)45000N/AN/ADetails
BrinzolamideCarbonic anhydrase 2Ki (nM)3N/AN/ADetails
CelecoxibCarbonic anhydrase 2Ki (nM)21N/AN/ADetails
DiclofenamideCarbonic anhydrase 1Ki (nM)1200N/AN/ADetails
DiclofenamideCarbonic anhydrase 2Ki (nM)38N/AN/ADetails
DorzolamideCarbonic anhydrase 1Ki (nM)50000N/AN/ADetails
DorzolamideCarbonic anhydrase 2Ki (nM)9N/AN/ADetails
EthoxzolamideCarbonic anhydrase 1Ki (nM)25N/AN/ADetails
EthoxzolamideCarbonic anhydrase 2Ki (nM)8N/AN/ADetails
SulpirideCarbonic anhydrase 2Ki (nM)40N/AN/ADetails
SulthiameCarbonic anhydrase 2Ki (nM)9N/AN/ADetails
TopiramateCarbonic anhydrase 1Ki (nM)250N/AN/ADetails
TopiramateCarbonic anhydrase 2Ki (nM)10N/AN/ADetails
ValdecoxibCarbonic anhydrase 2Ki (nM)43N/AN/ADetails
ZonisamideCarbonic anhydrase 1Ki (nM)56N/AN/ADetails
ZonisamideCarbonic anhydrase 2Ki (nM)35N/AN/ADetails