Carbonic anhydrase inhibitors. Diazenylbenzenesulfonamides are potent and selective inhibitors of the tumor-associated isozymes IX and XII over the cytosolic isoforms I and II.

Article Details

Citation
Copy to clipboard

Carta F, Maresca A, Scozzafava A, Vullo D, Supuran CT

Carbonic anhydrase inhibitors. Diazenylbenzenesulfonamides are potent and selective inhibitors of the tumor-associated isozymes IX and XII over the cytosolic isoforms I and II.

Bioorg Med Chem. 2009 Oct 15;17(20):7093-9. doi: 10.1016/j.bmc.2009.09.003. Epub 2009 Sep 6.

PubMed ID
19773173 [ View in PubMed
]
Abstract

A series of diazenylbenzenesulfonamides, azo-dye derivatives of sulfanilamide or metanilamide incorporating phenol and amine moieties, were tested for inhibition of the tumor-associated isozymes of carbonic anhydrase (CA, EC 4.2.1.1), CA IX and XII. These compounds showed moderate-low inhibitory activities against the cytosolic isoforms CA I and II (offtargets) and excellent, low nanomolar inhibitory activity against the transmembrane CA IX and XII (K(I)s in the range of 3.5-63 nM against CA IX and 5.0-69.4 nM against CA XII, respectively). The selectivity ratio for inhibiting the tumor-associated CA IX over the offtarget CA II was in the range of 15-104 for these diazenylbenzenesulfonamides, making them among the most isoform-selective inhibitors targeting tumor-associated CAs (over the ubiquitous CA II). Since CA IX/XII were recently shown to be both therapeutic and diagnostic targets for hypoxic solid tumors overexpressing these proteins, such compounds held promise for the management of hypoxic tumors, which are largely non-responsible to classical chemo- and radio-therapy.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AcetazolamideCarbonic anhydrase 1Ki (nM)2507.425Details
AcetazolamideCarbonic anhydrase 12Ki (nM)5.77.425Details
AcetazolamideCarbonic anhydrase 2Ki (nM)127.425Details
DorzolamideCarbonic anhydrase 1Ki (nM)500007.425Details
DorzolamideCarbonic anhydrase 2Ki (nM)97.425Details