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

Abstract

© 2018 Elsevier B.V. Two piano-stool ruthenium(II) complexes [Ru(η6-p-cymene)(N-MeIm)3]Cl2·2H2O (1) and [Ru(η6-p-cymene)(N-PrIm)Cl2] (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, Kb 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.