Synthesis, antiproliferative activity and apoptosis-promoting effects of arene ruthenium(II) complexes with N, O chelating ligands

New half sandwich arene ruthenium(II) complexes of the type [Ru(arene) Cl(L)] (where arene-benzene and p-cymene, L = thiophene benzhydrazone ligands) have been synthesized from the reactions of the neutral precursor [Ru(arene) (m-Cl) Cl] 2 and the corresponding benzhydrazone ligand. All the complexes were completely characterized by elemental analysis and additionally by IR, UV-Vis, H-1 NMR and ESI-MS spectroscopic methods. The solid state structures of the complexes 6 and 7 were determined by single-crystal X-ray diffraction analysis, which exhibit typical pseudo-octahedral geometry around the metal centre. The antiproliferative activity of the complexes was evaluated on cancerous (HeLa, MDA-MB-231, and Hep G2) and noncancerous (NIH3T3) cell lines. In general, complexes containing electron releasing OCH3 substituent have potential anticancer activity than those incorporating H, Cl and Br substituents. Moreover, the p-cymene complexes show more cytotoxicity than benzene derivatives, suggesting that the substituent at arene plays a vital role in the biological activity of the compounds. Further, an apoptotic mechanism of cell death in MDA-MB-231 was confirmed by AO-EB, Hoechst 33258 staining and annexin-V/PI double-staining techniques. In addition, the extent of DNA fragmentation in cancer cells was studied by comet assay. (C) 2018 Elsevier B.V. All rights reserved.