Carbonic anhydrase inhibitors. Inhibition of the cytosolic human isozymes I and II, and the transmembrane, tumor-associated isozymes IX and XII with substituted aromatic sulfonamides activatable in hypoxic tumors.

Article Details

Citation

Saczewski F, Slawinski J, Kornicka A, Brzozowski Z, Pomarnacka E, Innocenti A, Scozzafava A, Supuran CT

Carbonic anhydrase inhibitors. Inhibition of the cytosolic human isozymes I and II, and the transmembrane, tumor-associated isozymes IX and XII with substituted aromatic sulfonamides activatable in hypoxic tumors.

Bioorg Med Chem Lett. 2006 Sep 15;16(18):4846-51. Epub 2006 Jun 30.

PubMed ID
16809036 [ View in PubMed
]
Abstract

Some 2-mercapto-substituted-benzenesulfonamides and their disulfides/sulfones were prepared and investigated as inhibitors of four isoforms of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), that is, CA I and II (cytosolic enzymes), and the tumor-associated CA IX and XII. Some mercaptans led to a consistent increase of inhibitory power (52.8- to 243-fold) over the corresponding oxidized (S-S type) derivatives, acting as potential hypoxia-activatable drugs.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AcetazolamideCarbonic anhydrase 1Ki (nM)900N/AN/ADetails
AcetazolamideCarbonic anhydrase 12Ki (nM)5.7N/AN/ADetails
AcetazolamideCarbonic anhydrase 2Ki (nM)12N/AN/ADetails
DiclofenamideCarbonic anhydrase 1Ki (nM)1200N/AN/ADetails
DiclofenamideCarbonic anhydrase 2Ki (nM)38N/AN/ADetails
EthoxzolamideCarbonic anhydrase 1Ki (nM)25N/AN/ADetails
EthoxzolamideCarbonic anhydrase 2Ki (nM)8N/AN/ADetails