Gold(I)-mediated inhibition of protein tyrosine phosphatases: a detailed in vitro and cellular study.
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.
Krishnamurthy
Divya
D
Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
Karver
Mark R
MR
Fiorillo
Edoardo
E
Orrú
Valeria
V
Stanford
Stephanie M
SM
Bottini
Nunzio
N
Barrios
Amy M
AM
D002460:Cell Line; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017612:Gold Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004791:Enzyme Inhibitors; D017612:Gold Compounds; D017027:Protein Tyrosine Phosphatases