[Au-2(phen(2Me))(2)(mu-O)(2)](PF6)(2), a Novel Dinuclear Gold(III) Complex Showing Excellent Antiproliferative Properties

Maria A. Cinellu*, Laura Maiore, Mario Manassero, Angela Casini, Massimiliano Arca, Heinz-Herbert Fiebig, Gerhard Kelter, Elena Michelucci, Giuseppe Pieraccini, Chiara Gabbiani, Luigi Messori

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

68 Citations (Scopus)

Abstract

A novel dioxo-bridged dinuclear gold(III) complex with two 2,9-dimethylphenanthroline ligands was synthesized and thoroughly characterized. Its crystal structure was solved, and its solution behavior assessed. Remarkably, this compound revealed excellent antiproliferative properties in vitro against a wide panel of 36 cancer cell lines, combining a high cytotoxic potency to pronounced tumor selectivity. Very likely, these properties arise from an innovative mode of action (possibly involving histone deacetylase inhibition), as suggested by COMPARE analysis. In turn, electrospray ionization-mass spectrometry studies provided valuable insight into its molecular mechanisms of activation and of interaction with protein targets. Gold (III) reduction, dioxo bridge-disruption, coordinative gold(I) binding to the protein, and concomitant release of the phenanthroline ligand were proposed to occur upon interaction with superoxide dismutase, used here as a model protein. Because of the reported results, this new gold(III) compund qualifies itself as an optimal candidate for further pharmocological testing.

Original languageEnglish
Pages (from-to)336-339
Number of pages4
JournalBioorganic & Medicinal Chemistry Letters
Volume1
Issue number7
DOIs
Publication statusPublished - Oct-2010
Externally publishedYes

Keywords

  • Cytotoxic gold compounds
  • COMPARE analysis
  • protein targets
  • anticancer agents
  • ANTICANCER AGENTS
  • PROTEIN INTERACTIONS
  • SOLUTION CHEMISTRY
  • DRUGS
  • CISPLATIN
  • DNA

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