Synthesis and structure of new binuclear ruthenium(ii) arene benzil bis(benzoylhydrazone) complexes: investigation on antiproliferative activity and apoptosis induction

Abstract

A series of binuclear ruthenium(II) arene benzil bis(benzoylhydrazone) complexes (1–6) of the common composition [(η⁶-arene)₂Ru₂(L)Cl₂] (arene = benzene or p-cymene; L = benzil bis(benzoylhydrazone derivatives)) have been synthesized. The synthesised complexes have been thoroughly characterised by elemental analysis, IR, NMR, UV-vis and ESI-MS spectral methods. The coordination of the binucleating ligand to each ruthenium centre through azomethine nitrogen and imidolate oxygen was confirmed by single crystal XRD, which indicates the presence of the pseudo octahedral geometry. All the complexes were carefully screened for their cytotoxicity against HeLa, MDA-MB-231 and Hep G2 cells under in vitro conditions. Interestingly, the complexes 4 and 6 exhibit higher cytotoxicity than cisplatin, with low IC₅₀ values against all screened cancer cell lines. Furthermore, the mode of cell death in MDA-MB-231 cells was assessed by AO-EB, Hoechst 33258 staining and a flow cytometry technique along with the comet assay. The result of western blot analysis suggests that complexes 4 and 6 were shown to induce apoptosis via the mitochondrial pathway by up-regulating p53 and Bax, and down-regulating Bcl-2.