Ruthenium(II) Complexes containing anti-inflammatory drugs as ligands: Synthesis, characterization and in vitro cytotoxicity activities on cancer cell lines

Abstract

The synthesis, characterization and cytotoxic activity of cis-[Ru(dicl)(dppm)2]PF6 and cis.[Ru(ibu)(dppm)2]PF6, (dppm = 1,1-bis(diphenylphosphine)methane; dicl = diclofenac anion and ibu = ibuprofen anion), are described in this work. Complexes were characterized by elemental analysis, Fourier transform infrared spectroscopy (FTIR), UV-Vis, 31P{1H} nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRESIMS). X-ray structure of cis-[Ru(ibu)(dppm)2]PF6 is also described. Preliminary calf thymus DNA (ct-DNA) binding studies were carried out by UV-Vis and viscosity experiments, with results suggesting the existence of electrostatic interactions between ruthenium complexes and ct-DNA. Cytotoxicity assays were carried out on a panel of human cancer cell lines and a human normal cell line. Complexes displayed a high to moderate cytotoxicity with IC50 ranging from 5 to 47 μmol L-1. cis-[Ru(ibu) (dppm)2]PF6 was found to be the most active, with IC50 values lower than cisplatin. The degree of cytotoxicity was maintained for the normal cell line, although cis-[Ru(ibu)(dppm)2]PF6 exhibited a similar selectivity to that of cisplatin but with a higher activity for at least two tumor cell lines which evidences a promising anticancer candidate and selects this complex for further experiments.