title: [Au2(phen(2Me))2(μ-O)2](PF6)2, a Novel Dinuclear Gold(III) Complex Showing Excellent Antiproliferative Properties.
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) compound qualifies itself as an optimal candidate for further pharmacological testing.
authors.affiliation: Department of Chemistry, University of Sassari, Via Vienna 2, 07100 Sassari, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Cinellu
authors.affiliation: Department of Chemistry, University of Sassari, Via Vienna 2, 07100 Sassari, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Maiore
authors.affiliation: Department of Structural Chemistry and Inorganic Stereochemistry, University of Milano, Via Venezian 21, 20133 Milano, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Manassero
authors.affiliation: Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL) CH-1015 Lausanne, Switzerland.
authors.forename: Angela
authors.initials: A
authors.lastname: Casini
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Cagliari, S.S. 554 bivio per Sestu, 09042 Monserrato (CA), Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Arca
authors.affiliation: Institute for Experimental Oncology, Oncotest GmbH, Am Flughafen 12-14, D-79108 Freiburg, Germany.
authors.forename: Heinz-Herbert
authors.initials: HH
authors.lastname: Fiebig
authors.affiliation: Institute for Experimental Oncology, Oncotest GmbH, Am Flughafen 12-14, D-79108 Freiburg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Kelter
authors.affiliation: Mass Spectrometry Centre (CISM), University of Florence, Via U. Schiff 6, 50019 Sesto Fiorentino, Firenze, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Michelucci
authors.affiliation: Mass Spectrometry Centre (CISM), University of Florence, Via U. Schiff 6, 50019 Sesto Fiorentino, Firenze, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pieraccini
authors.affiliation: Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Firenze, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Gabbiani
authors.affiliation: Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Firenze, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Messori
keywords: COMPARE analysis; Cytotoxic gold compounds; anticancer agents; protein targets