Diphenylphosphine/Ru(II) complexes with antitumor activity: interactions with DNA and with HSA

Ruthenium/phosphine complexes are good examples of potential antitumor metallodrugs1. Thus, given the promising results reported in the literature involving ruthenium/phosphine complexes as potential antitumor drugs, herein we synthesize, characterize and investigate new complex and their effect cultured MDA-MB-231 and A549 tumor cells. Here, we also study the binding of the complexes to DNA and HAS biomolecules. The complexes, with general formula [Ru(tzdt)(bipy)(P-P)]PF6 and [Ru(MIm)(bipy)(P-P)]PF6, where P-P= 1,1′-bis(diphenylphosphino)ferrocene and (oxydi-2,1-phenylene)bis(diphenylphosphine); bipy= 2,2'-bipyridine; tzdt= 2-mercapto-2-thiazoline) and MIm= 2-mercapto-1-methyl-imidazole. The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay was used for the determination of the activity of the complexes. The IC50 for the complexes [Ru(tzdt)(bipy)(POP)]PF6 and [Ru(MIm)(bipy)(dppf)]PF6 are about 0.10 μM for the lung tumor cells A549 and about 0.29 μM for the breast tumor cells, respectively. The mechanism death for the cells, induced by the complexes are mainly by apoptosis. The complexes present weak electrostatic interaction with the DNA and their interaction with the HSA biomolecule occurs preferentially by the FA7 (site I). The complexes present promising results with IC50 values comparable with the reference drug cisplatin and high selectivity indexes were found. The IC50 of the complexes and their interaction with the biomolecules will be related with their structures.