Synthesis and structure of arene ruthenium(II) benzhydrazone complexes: Antiproliferative activity, apoptosis induction and cell cycle analysis

Abstract

Synthesis of new half-sandwich ruthenium (II) complexes of the type [Ru (η6-arene) (L)Cl] (arene = benzene or p-cymene; L = 1-pyrene-carboxaldehye benzhydrazone ligands) has been described. The synthesised complexes were completely characterised by elemental analysis and spectral (FT-IR, UV–vis, Emission, NMR and HRMS) methods. The isolated arene Ru(II) complexes are fluorescent in nature resulting the emission maxima observed in the visible region. The solid state molecular structures of the complexes 1, 2, 3 and 5 evidence that the ligands coordinate to ruthenium in a chelating κ2 N, O- bidentate fashion, and shows the presence of typical pseudo-octahedral geometry. The potential of the complexes to act as anticancer agents are thoroughly screened on breast adenocarcinoma MCF-7, lung adenocarcinoma A549 and NIH-3T3 cell lines by in vitro experimental conditions. The anticancer activity of complex 4 is found to be remarkable towards A549 with high selectivity index and low IC50 values compared to cisplatin. The differences in biological activity of the complexes were explained on the basis of partition coefficient values and differences in the energy of ruthenium–chloride bonds. Further, AO/EB, Hoechst 33258 and flow cytometry analyses indicate that present ruthenium complexes cause cell death only via apoptosis mechanism. The DNA content in cell cycle distribution was analysed by flow cytometry which shows that complex 4 suppress the cell growth in A549 cells at sub G0/G1 phase region, indicative of apoptotic cells. This study outlines the preliminary steps towards understanding the mechanism of action with a new class of ruthenium-based chemotherapeutics.