Synthesis, Characterization, Cytotoxic Activity, and Metabolic Studies of Ruthenium(II) Polypyridyl Complexes Containing Flavonoid Ligands.

Four novel monocationic Ru(II) polypyridyl complexes were synthesized with the general formula [Ru(DIP)2 flv]X, where DIP is 4,7-diphenyl-1,10-phenanthroline, flv stands for the flavonoid ligand (5-hydroxyflavone in [Ru(DIP)2 (5-OHF)](PF6 ), genistein in [Ru(DIP)2 (gen)](PF6 ), chrysin in [Ru(DIP)2 (chr)](OTf), and morin in [Ru(DIP)2 (mor)](OTf)), and X is the counterion, PF6 - , and OTf ̅ (triflate, CF3 SO3 ̅), respectively. Following the chemical characterization of the complexes by 1 H and 13 C NMR, mass spectrometry, and elemental analysis, their cytotoxicity was tested against several cancer cell lines. The most promising complex, [Ru(DIP)2 (gen)](PF6 ), was further investigated for its biological activity. Metabolic studies revealed that this complex severely impaired mitochondrial respiration and glycolysis processes, contrary to its precursor, Ru(DIP)2 Cl2 , which showed a prominent effect only on the mitochondrial respiration. In addition, its preferential accumulation in MDA-MB-435S cells (a human melanoma cell line previously described as mammary gland/breast; derived from metastatic site: pleural effusion), which are used for the study of metastasis, explained the better activity in this cell line compared to MCF-7 (human, ductal carcinoma).