Cytotoxic and anticancer properties of new ruthenium polypyridyl complexes with different lipophilicities

Three ruthenium complexes containing a bidentate piq ligand, [(piq)Ru(bpy)2]2+ (1), [(piq)Ru(phen)2]2+ (2), and [(piq)Ru(DIP)2]2+ (3) (piq = phenylisoquinolinate, bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline, DIP = 4,7-diphenyl-1,10-phenanthroline), were prepared. The DNA binding properties of complexes 1–3 to double-stranded DNA were studied. The binding of 1–3 to calf-thymus DNA (ct-DNA) yielded lower emission intensities than those observed with the corresponding Ru complexes alone. To explore potential interactions of complexes 1–3 with lipid-rich organs in live cells, the emission properties of the Ru probes were studied with liposomes. The emission intensities of complexes 1–3 were enhanced to similar extents upon interaction with liposomes. The cytotoxic activities of the complexes against MDA-MB-231 and HUVECs were evaluated in vitro. The effects of complexes 1–3 on the survival of MDA-MB-231 cells were examined and compared with that of cis-platin. Complexes 2 and 3 were more cytotoxic to cancer cells than cis-platin. Complexes 1–3 showed cellular uptakes of 1.1, 10.6, and 76.6%, respectively, indicating that the greatest amount of complex 3 entered the cancer cells. Inhibition of cell migration by complexes 1–3 was also evaluated by the wound healing assay. The anticancer properties of three Ru(II) complexes are significantly ligand-dependent and the lipophilicity of complexes enhances cellular uptake and anticancer activity. [Display omitted] •The ligand-dependent cytotoxicities of ruthenium polypyridyl complexes to cancer cells•Effect of ligand lipophilicity on antiproliferation and cellular uptake of cancer cells•Interaction of Ru complexes with DNA and liposomes