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A new ligand dmdppz and its four ruthenium(II) polypyridyl complexes [Ru(dmb) 2 (dmdppz)](ClO 4 ) 2 ( 1 ), [Ru(bpy) 2 (dmdppz)](ClO 4 ) 2 ( 2 ), [Ru(phen) 2 (dmdppz)](ClO 4 ) 2 ( 3 ) and [Ru(dmp) 2 (dmdppz)](ClO 4 ) 2 ( 4 ) (where dmb, bpy, phen, dmp and dmdppz stand for 4,4′-dimethyl-2,2′-bipyridine, 2,2′-bipyridine, 1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline and 5,8-dimethoxylpyrido[3,2- a :2′,3′- c ]phenazine, respectively) have been synthesized and characterized. Their DNA binding behaviors show that the complexes bind to calf thymus DNA by intercalation. The complexes exhibit efficient photocleavage of pBR322 DNA on irradiation. The cytotoxicity of the ligand and the complexes toward HepG-2, HeLa, MG-63, A549 and BEL-7402 were assayed by MTT ((3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyltetrazolium bromide)) method. The IC 50 values of the complexes 1 , 2 , 3 and 4 toward BEL-7402 cells are 14.6, 16.8, 18.0 and 16.7 μM, respectively. Dmdppz shows no cytotoxic activity against selected cell lines. The cellular uptake, apoptosis, comet assay, reactive oxygen species (ROS), mitochondrial membrane potential and western blot analysis were investigated. These results indicate that complexes 1 – 4 exert their toxicity through the intrinsic ROS-mediated mitochondrial pathway, which is accompanied by the regulation of Bcl-2 family proteins. [ABSTRACT FROM AUTHOR]

Two novel ruthenium(II) complexes [Ru(dmb)2(addppn)](ClO4)2 (1) and [Ru(bpy)2(addppn)](ClO4)2 (2) were synthesized. The DNA-binding constants of complexes 1 and 2 were determined to be 4.78 (±0.49) × 105 and 7.42 (±0.53) × 105 M−1. The results indicate that complexes 1 and 2 interact with CT DNA through intercalative mode. The cytotoxicity in vitro of the complexes toward BEL-7402, HeLa, MG-63 and SKBR-3 cells was assessed by MTT assay. The apoptosis was carried out with Hoechst 33258 staining method and flow cytometry. The cellular uptake was observed under fluorescence microscope. The cell cycle arrest shows that the antiproliferative mechanism induced by complexes 1 and 2 on BEL-7402 cells is G0/G1 phase arrest. [ABSTRACT FROM AUTHOR]