Further insights into ruthenium(II) piano-stool complexes with N-alkyl imidazoles

Abstract Two piano-stool ruthenium(II) complexes [Ru( η 6 - p -cymene)( N -MeIm) 3 ]Cl 2 ·2H 2 O ( 1 ) and [Ru( η 6 - p -cymene)( N -PrIm)Cl 2 ] ( 2 ) respectively have been synthesized and characterized by elemental, spectral and structural analysis. Crystal structures of ( 1 ) and ( 2 ) have been verified by X-ray diffraction analysis. Docking experiments toward DNA dodecamer have been done. Good ΔG binding values of the complexes with imidazole derivatives comparable with ethylene-diamine complex indicate a high potential of these compounds in the formation of DNA lesions and therefore their good cytotoxic status. The interaction of CT-DNA with ruthenium(II) complexes has been studied by means of absorption and fluorescence measurements. The binding constant, K b and the Stern–Volmer quenching constant reveal that complex ( 2 ) binds well to CT-DNA. The cytotoxic activity of Ru(II) complexes with N- RIm (R = methyl or propyl) were evaluated by MTT assay. A-549, HT-29 and HeLa cells were sensitive to all compounds tested, while the breast carcinoma cell line MCF-7 was resistant only to the complex ( 1 ). Flow cytometric analysis and fluorescent microscopy showed that ruthenium(II) complexes in HeLa cells induce apoptosis and G0/G1 cell cycle arrest and almost completely inhibit DNA synthesis. Western blot also demonstrated proteolytic cleavage of poly-(ADP-ribose) polymerase (PARP) in HeLa cells after treatment with both tested substances.