Complexes of platinum(II/IV) with 2-phenylpyridine derivatives as a new class of promising anti-cancer agents

Abstract

Four platinum(II/IV) complexes, [PtIV(PPy)2Cl2]·CH3OH (Pt1), [PtIV(TFPy)2Cl2] (Pt2), [PtII(MPy)(H-MPy)Cl] (Pt3), and [PtII(DPPy)(H-DPPy)Cl] (Pt4) with 2-phenylpyridine (H-PPy), 2-(4-trifluoromethylphenyl)pyridine (H-TFPy), 3-methyl-2-phenylpyridine (H-MPy) and 2,5-diphenylpyridine (H-DPPy) were first designed and prepared. Cytotoxic properties of Pt1–Pt4 were evaluated in human tumor HeLa (cervical), MCF-7 (breast), Hep-G2 (hepatoma), T-24 (bladder) cells and HL-7702 nontumorigenic cells by means of the MTT assay. The four Pt complexes Pt1–Pt4 were more selective for HeLa (cervical) cells versus normal HL-7702 cells. Remarkably the most active Pt2 compound, having 2-(4-trifluoromethylphenyl)pyridine (H-TFPy) ligand, showed IC50 values down to 1.01 ± 0.34 μM. Importantly, Pt1 and Pt2 induce apoptosis in T-24 (bladder) cells via ROS-mediated mitochondria dysfunction.