Hong-Liang Huang

Synthesis, DNA-binding, photocleavage, cytotoxicity and antioxidant activity of ruthenium (II) polypyridyl complexes

Two new ligands maip (1a), paip (1b) with their ruthenium (II) complexes [Ru(bpy)(2)(maip)](ClO(4))(2) (2a) and [Ru(bpy)(2)(paip)](ClO(4))(2) (2b) have been synthesized and characterized. The results show that complexes 2a and 2b interact with DNA through intercalative mode. The cytotoxicity of these compounds has been evaluated by MTT assay. The experiments on antioxidant activity show that these compounds exhibit good antioxidant activity against hydroxyl radical (OH).

Synthesis of ruthenium(II) complexes and characterization of their cytotoxicity in vitro, apoptosis, DNA-binding and antioxidant activity

A new ligand DBHIP and its two ruthenium (II) complexes [Ru(bpy)(2)(DBHIP)](ClO(4))(2) (1) and [Ru(phen)(2)(DBHIP)](ClO(4))(2) (2) have been synthesized and characterized. The binding behaviors of the two complexes to calf thymus DNA were investigated by absorption spectra, viscosity measurements, thermal denaturation and photoactivated cleavage. The DNA-binding constants for complexes 1 and 2 have been determined to be 8.87+/-0.27 x 10(4)M(-1) (s=1.83) and 1.32+/-0.31 x 10(5)M(-1) (s=1.84). The results suggest that these complexes interact with DNA through intercalative mode. The cytotoxicity of DBHIP, complexes 1 and 2 has been evaluated by MTT assay. The apoptosis assay was carried out with acridine orange/ethidium bromide (AO/EB) staining methods. The studies on the mechanism of photocleavage demonstrate that superoxide anion radical (O(2)(-)) and singlet oxygen ((1)O(2)) may play an important role.

The induction of apoptosis in BEL-7402 cells through the ROS-mediated mitochondrial pathway by a ruthenium(II) polypyridyl complex

A new Ru(II) polypyridyl complex [Ru(phen)2(addppn)](ClO4)2 (Ru1) has been synthesized and characterized. The DNA-binding constant of the complex with DNA was determined to be 1.93 (±0.12) × 106 M−1. The complex interacts with DNA by an intercalative mode. Cytotoxicity in vitro, apoptosis, cell cycle distribution, apoptotic pathway, reactive oxygen species and mitochondrial membrane potential assays were performed. The IC50 values of Ru1 toward BEL-7402, HeLa, MG-63 and SKBR-3 cell lines are 3.9 ± 0.4, 9.0 ± 0.8, 6.6 ± 0.6 and 5.1 ± 0.6 μM, respectively. Interestingly, Ru1 shows a higher cytotoxicity than cisplatin on BEL-7402 cells under identical conditions. Ru1 can effectively induce apoptosis in BEL-7402 and induces cell cycle arrest at the G0/G1 phase in BEL-7402 cells and at the G2/M phase in SKBR-3 cells. In addition, Ru1 can enhance the level of reactive oxygen species and induce the decrease of the mitochondrial membrane potential. Western blot analysis shows that Ru1 activates caspase-3 and -7, down-regulates the expression of the anti-apoptotic proteins of Bcl-x and Bag-1, and upregulates the levels of the proapoptotic proteins of Bad, Bak, Bax and Bim in BEL-7402 cells. These results show that Ru1 induces apoptosis in BEL-7402 cells through an ROS-mediated mitochondrial dysfunction pathway.

Synthesis, characterization, DNA interaction, antioxidant and anticancer activity studies of ruthenium(II) polypyridyl complexes.

Two new Ru(II) polypyridyl complexes [Ru(phen)₂(adppz)](ClO₄)₂ (1) and [Ru(dip)₂(adppz)](ClO₄)₂ (2) have been synthesized and characterized. The DNA-binding constants were determined to be 6.54 ± 0.42 × 10(5) and 7.65 ± 0.20 × 10(5)M(-1) for complexes 1 and 2. DNA binding experiments indicated that complexes 1 and 2 interact with DNA through intercalative mode. Antioxidant activity shows that the complexes have significant hydroxyl radical scavenging activity. Cytotoxic activities suggest that the complex 2 exhibits higher cytotoxic activity against BEL-7402, MG-63 and SKBR-3 cells than complex 1 under identical conditions. Complexes 1 and 2 can induce apoptosis of BEl-7402 cells. We have identified several cellular mechanisms induced by 1 and 2 in BEL-7402 cells, including the level detection of ROS, activation of procaspase 3, caspase 7, the expression of antiapoptotic proteins Bcl-x, Bcl-2, proapoptotic proteins Bad, Bax, Bid and cell cycle arrest. Thus, complexes 1 and 2 inhibit growth of BEL-7402 cells through induction of apoptotic cell death, enhancement of ROS levels and S-phase and G0/G1 cell cycle arrest. Further investigations have shown that complex 2 induces apoptosis by regulating the expression of Bcl-2 family proteins.

Ruthenium(II) complexes: DNA-binding, cytotoxicity, apoptosis, cellular localization, cell cycle arrest, reactive oxygen species, mitochondrial membrane potential and western blot analysis.

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)](ClO₄)₂ (1), [Ru(bpy)₂(HMHPIP)](ClO₄)₂ (2), [Ru(phen)₂(HMHPIP)](ClO₄)₂ (3) and [Ru(dmp)₂(HMHPIP)](ClO₄)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.

Synthesis, structure, DNA-binding properties, and cytotoxicity of ruthenium(II) polypyridyl complexes.

Many ruthenium(II) complexes show high antitumor activities, and the in vitro antitumor activities are usually related to DNA binding. We designed and synthesized two RuII polypyridyl complexes, [Ru(dmp)2(fpp)]2+ (dmp=2,9‐dimethyl‐1,10‐phenanthroline; fpp=2‐[3,4‐(difluoromethylenedioxy)phenyl]imidazo[4,5‐f] [1,10]phenanthroline and [Ru(phen)2(fpp)]2+ (phen=1,10‐phenanthroline). The DNA‐binding properties of these complexes have been investigated by spectroscopic titration, DNA melting experiments, viscosity measurements, and photoactivated cleavage. The mechanism studies of photocleavage revealed that singlet oxygen (1O2) and superoxide anion radical (O

In vitro cytotoxicity, apoptosis, DNA-binding, and antioxidant activity studies of ruthenium (II) complexes.

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Synthesis, characterization, in vitro cytotoxicity, and apoptosis-inducing properties of ruthenium(II) complexes.

) may play an important role in the photocleavage. The cytotoxicity of complexes 1 and 2 have been evaluated by MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide) method; complex 2 shows slightly higher anticancer potency than 1 does against all the cell lines screened.

Cytotoxicity In Vitro, Apoptosis, Cellular Uptake, Cell Cycle Distribution, Mitochondrial Membrane Potential Detection, DNA Binding, and Photocleavage of Ruthenium(ii) Complexes

Two new ligands maip (1) (maip = 2-(3-aminophenyl)imizado[4,5-f][1,10]phenanthroline), paip (2) (paip = 2-(4-aminophenyl)imidazo[4,5-f][1,10]phenanthroline), and their ruthenium (II) complexes [Ru(phen)(2)(maip)](ClO(4))(2) (3) and [Ru(phen)(2)(paip)](ClO(4))(2) (4) (phen = 1,10-phenanthroline) have been synthesized and characterized. The cytotoxicity of these compounds was evaluated by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The apoptosis assay was carried out with acridine orange/ethidium bromide staining methods. The DNA-binding behaviors of complexes 3 and 4 were investigated by viscosity measurements, thermal denaturation, photocleavage, and spectroscopic methods. The results show that the two complexes intercalate into the base pairs of DNA. In the presence of a complex, apoptosis of BEL-7402 cells was observed. Experiments show that these compounds exhibit antioxidant activity against hydroxyl radicals.

Ruthenium(II) complexes: synthesis, cytotoxicity in vitro, apoptosis, DNA-binding, photocleavage, and antioxidant activity studies

Two new Ru(II) complexes, [Ru(bpy)2(FAMP)](ClO4)2 1 and 2, are synthesized and characterized by elemental analysis, electrospray mass spectrometry, and 1H nuclear magnetic resonance. The in vitro cytotoxicities and apoptosis-inducing properties of these complexes are extensively studied. Complexes 1 and 2 exhibit potent antiproliferative activities against a panel of human cancer cell lines. The cell cycle analysis shows that complexes 1 and 2 exhibit effective cell growth inhibition by triggering G0/G1 phase arrest and inducing apoptosis by mitochondrial dysfunction. The in vitro DNA binding properties of the two complexes are investigated by different spectrophotometric methods and viscosity measurements.