Chemistry and Biology of Two Novel Gold(I) Carbene Complexes as Prospective Anticancer Agents

• DOI: 10.1021/ic401731a
• Publication Date: 2014-02-18T14:43:25Z
• Authors: Luigi Messori; Lorella Marchetti; Lara Massai; Federica Scaletti; Annalisa Guerri; Ida Landini; Stefania Nobili; Gabriele Perrone; Enrico Mini; Piero Leoni; Marco Pasquali; Chiara Gabbiani
• Keywords: Imidazole; Reactivity; Auranofin; Gold Compounds

Two novel gold carbene compounds, namely, chlorido (1-butyl-3-methyl-imidazole-2-ylidene) gold(I) (1) and bis(1-butyl-3-methyl-imidazole-2-ylidene) (2), were prepared characterized as prospective anticancer drug candidates. These compounds consist of a center linearly coordinated either to one N-heterocyclic (NHC) chloride ligand or two identical NHC ligands (2). Crystal structures solved for both the resulting structural data being in good agreement with expectations. We wondered whether presence tight 2 might lead biological properties distinct from those monocarbene complex 1. Notably, spite their appreciable differences, these manifested similarly potent cytotoxic actions vitro when challenged against A2780 human ovarian carcinoma cells. In addition, able overcome resistance cisplatin A2780R line. Solution studies revealed that complexes are highly stable aqueous buffers at physiological pH. Their reactivity proteins was explored: no adduct formation detected even upon long incubation model cytochrome c lysozyme; contrast, metalate, large extent, copper chaperone Atox-1, bearing characteristic CXXC motif. The precise nature gold-Atox-1 adducts elucidated through ESI-MS analysis. On basis findings, it is proposed investigated promising antiproliferative agents warranting wider pharmacological evaluation. Most likely produce effects selective metalation impairment few crucial cellular proteins.