Carbonic anhydrase inhibitors: copper(II) complexes of polyamino-polycarboxylamido aromatic/heterocyclic sulfonamides are very potent inhibitors of the tumor-associated isoforms IX and XII.
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.
Institut des Biomolécules Max Mousseron UMR 5247 CNRS-UM1-UM2 Bâtiment de Recherche Max Mousseron, Ecole Nationale Supérieure de Chimie de Montpellier, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex, France.
Marouan
M
Rami
Jean-Yves
JY
Winum
Alessio
A
Innocenti
Jean-Louis
JL
Montero
Andrea
A
Scozzafava
Claudiu T
CT
Supuran
D000588:Amines / Q000737:chemistry; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000737:chemistry; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000201:enzymology*; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*
D000588:Amines; D002257:Carbonic Anhydrase Inhibitors; D006571:Heterocyclic Compounds; D007527:Isoenzymes; D013449:Sulfonamides; D003300:Copper