title: Gold(I)-mediated inhibition of protein tyrosine phosphatases: a detailed in vitro and cellular study.
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.
authors.affiliation: Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
authors.forename: Divya
authors.initials: D
authors.lastname: Krishnamurthy
authors.forename: Mark R
authors.initials: MR
authors.lastname: Karver
authors.forename: Edoardo
authors.initials: E
authors.lastname: Fiorillo
authors.forename: Valeria
authors.initials: V
authors.lastname: Orrú
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Stanford
authors.forename: Nunzio
authors.initials: N
authors.lastname: Bottini
authors.forename: Amy M
authors.initials: AM
authors.lastname: Barrios
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D017612:Gold Compounds; D017027:Protein Tyrosine Phosphatases