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Four new ruthenium(II) polypyridyl complexes [Ru(N–N) 2 (dhbn)](ClO 4 ) 2 (N–N = dmb: 4,4′-dimethyl-2,2′-bipyridine 1 ; bpy = 2,2′-bipyridine 2 ; phen = 1,10-phenanthroline 3 ; dmp = 2,9-dimethyl-1,10-phenanthroline 4 ) were synthesized and characterized. The cytotoxicity in vitro of the ligand and complexes toward HepG-2, HeLa, MG-63 and A549 were assayed by MTT method. The IC 50 values of the complexes against the above cells range from 17.7 ± 1.1 to 45.1 ± 2.8 μM. The cytotoxic activity of the complexes against HepG-2 cells follows the order of 4 > 2 > 3 > 1 . Ligand shows no cytotoxic activity against the selected cell lines. Cellular uptake, apoptosis, comet assay, reactive oxygen species, mitochondrial membrane potential, cell cycle arrest, and the expression of proteins involved in apoptosis pathway induced by the complexes were investigated. The results indicate that complexes 1–4 induce apoptosis in HepG-2 cells through an intrinsic ROS-mediated mitochondrial dysfunction pathway. [ABSTRACT FROM AUTHOR]

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]

The aim of our study was to investigate DNA-binding and cytotoxic activity of the four new Ru(II) polypyridyl complexes [Ru(dmb) 2 (HMHPIP)](ClO 4 ) 2 ( 1 ), [Ru(bpy) 2 (HMHPIP)](ClO 4 ) 2 ( 2 ), [Ru(phen) 2 (HMHPIP)](ClO 4 ) 2 ( 3 ) and [Ru(dmp) 2 (HMHPIP)](ClO 4 ) 2 ( 4 ). The complexes interact with DNA through intercalative mode and show relatively high cytotoxic activity against A549 cells, no cytotoxicity toward MG-63 cells. Complexes 1 – 4 can enhance the levels of ROS in A549 cells and induce the decrease of the mitochondrial membrane potential. These complexes inhibit the cell growth in A549 cells at G0/G1 or S phase. Complex 3 activated caspase 7, and down-regulated the expression of the anti-apoptotic protein Bcl-2. Complexes 1 – 4 induce apoptosis in A549 cells through ROS-mediated mitochondrial dysfunction pathway. [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]

Two new ruthenium(II) complexes, [Ru(phen)2(DNPIP)](ClO4)2 (1) and [Ru(phen)2(DAPIP)](ClO4)2 (2), were synthesized and characterized. The DNA-binding properties of these complexes were investigated using UV/vis absorption titration, viscosity measurements, thermal denaturation, and photoactivated cleavage. The DNA binding constants for complexes 1 and 2 are 2.63 ± 0.25 × 105 M−1 ( s = 2.45) and 1.51 ± 0.18 × 105 M−1 ( s = 1.34). The results indicated that these complexes interacted with DNA through the intercalative mode. The cytotoxicity in vitro of complexes 1 and 2 were assessed against BEL-7402, HepG-2, and MCF-7 cell lines by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was studied with the acridine orange/ethidium bromide staining method. The antiproliferative mechanism was explored with flow cytometry. Cellular uptake studies showed that complexes 1 and 2 can enter into the cytoplasm and accumulate in the nuclei. Cell cycle arrest and antioxidant activity were also investigated. [ABSTRACT FROM AUTHOR]