Ru(II)-diphosphine/N,S-mercapto complexes and their anti-melanoma properties

Abstract

We have synthesized and characterized a novel series of ruthenium complexes with formulas [RuCl(N–S)(dppm)2]PF6 (Ru1), [Ru(N–S)(dppm)2]PF6 (Ru2), [Ru(N–S)(dppe)2]PF6 (Ru3), [Ru(N–S)(dppen)2]PF6 (Ru4),[Ru(N–S)(bpy)2]PF6 (Ru5). In these formulas, N–S or S represents H2mq (2-mercapto-4(3H)-quinazoline); dppe (1,2’-bis(diphenylphosphine)ethane), dppm (1,1’-bis(diphenylphosphine)methane), or dppen (1,2’-bis (diphenylphosphine)ethene); and bpy refers to 2,2’-bipyridine. We have also compared the cytotoxicity of cisplatin with these ruthenium complexes to murine melanoma cells (B16-F10), human melanoma cells (A-375), and the non-tumoral human keratinocyte cell line (HaCat). All the ruthenium complexes inhibited melanoma cell growth in a dose-dependent manner. [Ru(2mq)(dppen)2]PF6 was four times more active toward A-375 cells than toward HaCat cells, inhibited colony formation in HaCat and A-375 cells (with a more pronounced effect on A-375 cells), altered A-375 cell morphology, and inhibited cell migration at 0.2 and 0.4 μM. In addition, we investigated how these ruthenium complexes interact with biomolecules such as DNA and Human Serum Albumin (HSA). All the ruthenium complexes interacted weakly with DNA, possibly through the grooves. Based on fluorescence assays, the ruthenium complexes interacted moderately with HSA. In light of these results, ruthenium complexes bearing phosphine and H2mq display promising cytotoxic properties against melanoma.