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 COM- PARE 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.
A novel dioxo-bridged dinuclear gold(III) complex with two 2,9- dimethylphenanthroline ligands was synthesized and thoroughly characterized. Its crystal structurewas 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 interactionwith 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.
[Au2(phen2Me)2(?-O)2](PF6)2, a novel dinuclear gold(III) complex showing excellent antiproliferative properties / Cinellu, Maria Agostina; Maiore, Laura; Manassero, M; Casini, A; Arca, M; Fiebig, H. H.; Kelter, G; Michelucci, E; Pieraccini, G; Gabbiani, C; Messori, L.. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - 1:(2010), pp. 336-339. [10.1021/ml100097f]
[Au2(phen2Me)2(?-O)2](PF6)2, a novel dinuclear gold(III) complex showing excellent antiproliferative properties
CINELLU, Maria Agostina;MAIORE, Laura;
2010-01-01
Abstract
A novel dioxo-bridged dinuclear gold(III) complex with two 2,9- dimethylphenanthroline ligands was synthesized and thoroughly characterized. Its crystal structurewas 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 interactionwith 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
