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. doi: 10.1016/j.bmcl.2007.11.025. Epub 2007 Nov 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Copper / chemistry
  • Heterocyclic Compounds / chemistry
  • Isoenzymes / antagonists & inhibitors*
  • Neoplasms / enzymology*
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*

Substances

  • Amines
  • Carbonic Anhydrase Inhibitors
  • Heterocyclic Compounds
  • Isoenzymes
  • Sulfonamides
  • Copper