Ruthenium(ii) arene complexes containing benzhydrazone ligands: synthesis, structure and antiproliferative activity

Abstract

A suitable method for the synthesis of ruthenium(II) arene benzhydrazone complexes (1–6) of the general formula [(η⁶-arene)Ru(L)Cl] (arene-benzene or p-cymene; L-monobasic bidentate substituted 9-anthraldehyde benzhydrazone derivatives) has been described. The composition of the complexes has been established by elemental analysis, IR, UV-Vis, emission, NMR and ESI-MS spectral methods. The solid state molecular structure of a representative complex was determined by a single-crystal X-ray diffraction study and indicates the presence of pseudo-octahedral (piano stool) geometry. All the complexes have been thoroughly screened for their cytotoxicity against human cervical cancer cells (HeLa), human breast cancer cell line (MDA-MB-231) and human liver carcinoma cells (Hep G2) under in vitro conditions. Interestingly, the cytotoxic activity of complex 6 is much more potent than cisplatin with low IC₅₀ values against all the cancer cell lines tested. Furthermore, the results of AO–EB, Hoechst 33258 and flow cytometry analyses reveal that these complexes induce cell death only through apoptosis. The comet assay has been employed to determine the extent of DNA fragmentation in cancer cells. A hemolysis assay with human erythrocytes demonstrated good blood biocompatibility of all the ruthenium(II) arene benzhydrazone complexes. These results highlight the strong possibility to develop highly active ruthenium complexes as anticancer agents.