Ruthenium(II) p-cymene complex bearing 2,2′-dipyridylamine targets caspase 3 deficient MCF-7 breast cancer cells without disruption of antitumor immune response

[Ru(η6-p-cym)Cl{dpa(CH2)4COOEt}][PF6] (cym=cymene; dpa=2,2′-dipyridylamine; complex 2) was prepared and characterized by elemental analysis, IR and multinuclear NMR spectroscopy, as well as ESI-MS and X-ray structural analysis. The structural analog without a side chain [Ru(η6-p-cym)Cl(dpa)][PF6] (1) as well as 2 were investigated in vitro against 518A2, SW480, 8505C, A253 and MCF-7 cell lines. Complex 1 is active against all investigated tumor cell lines while the activity of compound 2 is limited only to caspase 3 deficient MCF-7 breast cancer cells, however, both are less active than cisplatin. As CD4+Th cells are necessary to trigger all the immune effector mechanisms required to eliminate tumor cells, besides testing the in vitro antitumor activity of 1 and 2, the effect of ruthenium(II) complexes on the cells of the adaptive immune system have also been evaluated. Importantly, complex 1 applied in concentrations which were effective against tumor cells did not affect immune cell viability, nor did exert a general immunosuppressive effect on cytokine production. Thus, beneficial characteristics of 1 might contribute to the overall therapeutic properties of the complex. Synthesis and characterization of [Ru(η6-p-cym)Cl{dpa(CH2)4COOEt}][PF6] (cym=cymene; dpa=2,2′-dipyridylamine; 2) as well as its antitumor activity and that of [Ru(η6-p-cym)Cl(dpa)][PF6] (1) is described. The most prominent activity was observed for 1 against caspase deficient MCF-7 breast cancer cells without affect to the immune cells and cytokine production. [Display omitted] •[Ru(η6-p-cymene)Cl(dpaR)][PF6], dpa=2,2′-dipyridylamine; R=H (1), (CH2)4COOEt (2).•Ru(II) complex 1 is more active against tumor cells than 2.•1 is the most efficient against caspase 3 deficient MCF-7 breast cancer cells.•1 is not active against cells of the adaptive immune system.•1 does not exert a general immunosuppressive effect on cytokine production.