Preparation and characterization of amino-linked heterocyclic carbene palladium, gold, and silver complexes and their use as anticancer agents that act by triggering apoptotic cell death

J Med Chem. 2011 Jul 28;54(14):5245-9. doi: 10.1021/jm101096x. Epub 2011 Jun 28.

Abstract

Transition metal complexes bearing amino linked N-heterocyclic carbenes (NHC) were prepared and evaluated for their antiproliferative activities in human cancer cells. The optimum antiproliferative activity, observed for the gold complex 3 in U-87 MG cells, was found to involve S-phase arrest of the cell cycle. The results indicate that 3 induces apoptosis through a p53-bak pathway, a finding that could serve as a new strategy to reduce the resistance of cancer cells to p53-induced apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis*
  • Cell Line, Tumor
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology
  • Cyclin A / biosynthesis
  • Cyclin B / biosynthesis
  • Cyclin-Dependent Kinase 2 / biosynthesis
  • Drug Screening Assays, Antitumor
  • Gold*
  • Humans
  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry
  • Imidazoles / pharmacology
  • Methane / analogs & derivatives*
  • Methane / chemical synthesis
  • Methane / chemistry
  • Methane / pharmacology
  • Palladium*
  • S Phase
  • Silver*
  • Structure-Activity Relationship
  • Tumor Suppressor Protein p53 / physiology
  • bcl-2 Homologous Antagonist-Killer Protein / physiology

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Cyclin A
  • Cyclin B
  • Imidazoles
  • Tumor Suppressor Protein p53
  • bcl-2 Homologous Antagonist-Killer Protein
  • carbene
  • Silver
  • Palladium
  • Gold
  • Cyclin-Dependent Kinase 2
  • Methane