Cytotoxic Properties of a New Organometallic Platinum(II) Complex and its Gold(I) Heterobimetallic Derivatives

A novel platinum(II) organometallic complex, [Pt(pbi)(Me)(DMSO)], bearing the 2-(2’-pyridyl)-benzimidazole
(pbiH) ligand, was synthesized and fully characterized. Interestingly, the reaction of this organometallic
platinum(II) complex with two distinct gold(I) phosphane compounds afforded the corresponding
heterobimetallic derivatives with the pbi ligand bridging the two metal centers. The antiproliferative properties
in vitro of [Pt(pbi)(Me)(DMSO)] and its gold(I) derivatives as well as those of the known coordination
platinum(II) and palladium(II) complexes with the same ligand, of the general formula [MCl2(pbiH)], were
comparatively evaluated against A2780 cancer cells, either sensitive or resistant to cisplatin. A superior
biological activity of the organometallic compound clearly emerged compared to the corresponding
platinum(II) complex; the antiproliferative effects are further enhanced upon attaching the gold(I) triphenylphosphine
moiety to the organometallic Pt compound. Remarkably, these novel metal species are
able to overcome nearly complete resistance to cisplatin. Significant mechanistic insight into the study
compounds was gained after investigating their reactions with a few representative biomolecules by
electrospray mass spectrometry and X-ray crystallography. The obtained results are comprehensively
discussed.