Carbonic anhydrase inhibitors: copper(II) complexes of polyamino-polycarboxylamido aromatic/heterocyclic sulfonamides are very potent inhibitors of the tumor-associated isoforms IX and XII.

Article Details

Citation

Rami M, Winum JY, Innocenti A, Montero JL, Scozzafava A, Supuran CT

Carbonic anhydrase inhibitors: copper(II) complexes of polyamino-polycarboxylamido aromatic/heterocyclic sulfonamides are very potent inhibitors of the tumor-associated isoforms IX and XII.

Bioorg Med Chem Lett. 2008 Jan 15;18(2):836-41. Epub 2007 Nov 13.

PubMed ID
18042384 [ View in PubMed
]
Abstract

Reaction of EDTA/DTPA dianhydride with aromatic/heterocyclic sulfonamides afforded a series of derivatives incorporating polyaminopolycarboxylate tails and benzenesulfonamide or 1,3,4-thiadiazole-2-sulfonamide heads. These compounds have been used as ligands to prepare Cu(II) complexes. Both parent sulfonamides as well as their copper complexes behaved as potent inhibitors of four carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic CA I and II, and transmembrane CA IX and XII. Some Cu(II) complexes showed subnanomolar affinities and some selectivity for the inhibition of the tumor-associated isoforms IX and XII and might be used as PET hypoxia markers of tumors.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AcetazolamideCarbonic anhydrase 1Ki (nM)250N/AN/ADetails
AcetazolamideCarbonic anhydrase 12Ki (nM)5.7N/AN/ADetails
AcetazolamideCarbonic anhydrase 2Ki (nM)10N/AN/ADetails
EthoxzolamideCarbonic anhydrase 1Ki (nM)25N/AN/ADetails
EthoxzolamideCarbonic anhydrase 2Ki (nM)8N/AN/ADetails