Gold(I)-mediated inhibition of protein tyrosine phosphatases: a detailed in vitro and cellular study

J Med Chem. 2008 Aug 14;51(15):4790-5. doi: 10.1021/jm800101w. Epub 2008 Jul 8.

Abstract

Gold(I) complexes containing N-heterocyclic carbene ligands were synthesized, characterized, and along with the antiarthritic drug, auranofin, tested as inhibitors of the cysteine-dependent protein tyrosine phosphatases, which are implicated in several disease states. These compounds exhibit potencies in the low micromolar range against the enzymes in vitro. At therapeutically relevant concentrations, all compounds inhibit PTP activity in Jurkat T leukemia cells with some selectivity. In addition, the gold-carbene compounds inhibit phosphatase activity in primary mouse thymocytes.

MeSH terms

  • Cell Line
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Gold Compounds / chemical synthesis*
  • Gold Compounds / chemistry
  • Gold Compounds / pharmacology*
  • Humans
  • Hydrogen-Ion Concentration
  • Molecular Structure
  • Protein Tyrosine Phosphatases / antagonists & inhibitors*
  • Protein Tyrosine Phosphatases / metabolism

Substances

  • Enzyme Inhibitors
  • Gold Compounds
  • Protein Tyrosine Phosphatases