RESUMO
Ruthenium(II) complexes containing phenazine ring have attracted attention to design as 'molecular light switches'. In this study, we synthesized two ruthenium complexes containing phenazine ring and studied their abilities to function as DNA intercalators, DNA 'light switches', DNA topo I inhibitors, DNA photocleavers and potential antitumor reagents. [Ru(bpy)2(mbipz)](PF6)2 (1) (bpy = 2,2'-bipyridine, mbipz = 2-(4'-methyl-bipyridine-4-yl)-1H-imidazo[4,5-b]phenazine) exhibited off-on type DNA 'light swtich' behavior. DNA binding modes of the two complexes were determined as intercalation by using UV-vis spectra, emission spectra, viscosity and molecular docking experiments. DNA photocleavage experimental results showed that the two ruthenium complexes effectively cleave plasmid DNA by producing singlet oxygen. Furthermore, they displayed good topo I inhibition activities. We further found that the two complexes displayed good antitumor activities against Eca-109 cells and A549 cells. The results demonstrated that introduction of phenazine ring will be helpful to design DNA 'light switch' based on ruthenium complex.Communicated by Ramaswamy H. Sarma.
Assuntos
Rutênio , DNA , DNA Topoisomerases Tipo I , Simulação de Acoplamento Molecular , FenazinasRESUMO
A new strategy for a G-quadruplex fluorescent probe based on a nitro-substituted ruthenium complex is described. G-quadruplex DNA can be distinguished from double- or single-strand DNA by the naked eye. This ability originates from variation of the degree of protection of the nitro group on the complex from water by G-quadruplex and other structure DNAs.
Assuntos
Complexos de Coordenação/química , DNA/análise , Corantes Fluorescentes/química , Quadruplex G , Nitrobenzenos/química , Colorimetria/métodos , DNA/genética , Humanos , Rutênio/químicaRESUMO
A new ruthenium complex with a dppz-like ligand pyidppz, [Ru(bpy)2(pyidppz)](2+) (pyidppz = 2-(pyridine-2-yl)imidazo-[4,5-b]dipyrido-[3,2-a:2',3'-c]phenazine) has been synthesized and characterized by ES-MS, elemental analysis, (1)H NMR. Intercalative mode of the complex bound to calf thymus DNA has been supported by different spectroscopic methods and viscosity measurements. The introduction of phenazine unit may be one of the main reasons for the weak emission of Ru(II) complex in aqueous solution. Under irradiation, this complex can efficiently cleave DNA. And the photocleavage reaction of the complex is found to be inhibited in the presence of singlet oxygen scavenger. Topoisomerase inhibition and DNA strand passage assay demonstrated that [Ru(bpy)2(pyidppz)](2+) and its parent complex [Ru(bpy)2(pyip)](2+) (pyip = 2-(pyridine-2-yl)imidazo[4,5-f][1,10]phenanthroline) can act as efficient catalytic inhibitor of DNA topoisomerase I.
Assuntos
Clivagem do DNA/efeitos dos fármacos , DNA/química , Luz , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Fenazinas/química , Rutênio/química , Animais , Bovinos , DNA/metabolismo , Ligantes , Compostos Organometálicos/metabolismo , Inibidores da Topoisomerase I/química , Inibidores da Topoisomerase I/metabolismo , Inibidores da Topoisomerase I/farmacologiaRESUMO
Two new ruthenium complexes with [Ru(L)(2)(qip)](2+) (L=bpy (2,2'- bipyridine), phen (1,10-phenanthroline); qip=2-(2-quinolinyl)imidazo[4,5-f][1,10]phenanthroline), have been synthesized and characterized by elemental analysis, ES-MS, (1)H NMR. The binding properties of two complexes towards CT-DNA were investigated by various optical methods and viscosity measurements. The experiment results suggested that both Ru(II) complexes can intercalate into DNA base pairs. Strong quenching in emission intensity of two Ru(II) complexes were observed upon addition of Ag(+) in the absence and presence of CT-DNA. Furthermore, the two complexes can promote cleavage of pBR322 DNA under irradiation at 365 nm, and complex 2 exhibits a stronger DNA-photocleavage efficiency than complex 1. The mechanism of DNA cleavage suggests that singlet oxygen ((1)O(2)) is likely to be the cleaving agent.
Assuntos
2,2'-Dipiridil/análogos & derivados , DNA/metabolismo , Substâncias Intercalantes/química , Substâncias Intercalantes/farmacologia , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Fenantrolinas/química , Fenantrolinas/farmacologia , 2,2'-Dipiridil/química , 2,2'-Dipiridil/farmacologia , Animais , Bovinos , DNA/química , Clivagem do DNA/efeitos dos fármacos , Clivagem do DNA/efeitos da radiação , Imidazóis/química , Imidazóis/farmacologia , Medições Luminescentes , Processos Fotoquímicos , Prata/metabolismoRESUMO
A novel asymmetric ligand 2-(pyridine-2-yl)-1-H-imidazo[4,5-i]dibenzo[2,3-a:2',3'-c]phenazine (pidbp) and its ruthenium complexes [Ru(L)(2)(pidbp)](2+) (L=bpy (2, 2'- bipyridine), phen (1, 10 - phenanthroline)), have been synthesized and characterized by elemental analysis, ES-MS, (1)H NMR. Various methods support the conclusion that both Ru(II) complexes can intercalate into DNA base pairs. Complex [Ru(bpy)(2)(pidbp)](2+)4 exhibits its DNA "molecular light switch" properties. Furthermore, the two complexes are efficient DNA-photocleavers under irradiation at 365 nm, and complex 5 exhibits a stronger DNA-photocleavage efficiency than complex 4. The mechanism of DNA cleavage is an oxidative process by generating singlet oxygen.
Assuntos
Complexos de Coordenação/metabolismo , Clivagem do DNA/efeitos da radiação , DNA/metabolismo , Substâncias Intercalantes/metabolismo , Rutênio/metabolismo , Absorção/efeitos da radiação , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Elétrons , Eletroforese em Gel de Ágar , Etídio/química , Substâncias Intercalantes/química , Ligantes , Luz , Plasmídeos/metabolismo , Rutênio/química , Espectrometria de Fluorescência , Titulometria , Viscosidade/efeitos da radiaçãoRESUMO
The aim of this study was to detect the expression of the Forkhead box M1 (FOXM1) protein in human hepatocellular carcinoma (HCC) and to associate FOXM1 expression with clinicopathological features of the patients, and predict the prognosis of patients with FOXM1 expression. Surgical tissue specimens from 151 HCC patients were subjected to a tissue microarray construction and immunohistochemistry analysis of FOXM1 and the proliferation marker proliferating cell nuclear antigen (PCNA). The data showed that the FOXM1 protein was expressed in 59.3% of the HCC tissues, which was significantly higher compared to that of the surrounding non-tumorous tissues (23.8%; P<0.001). Moreover, FOXM1 expression was positively correlated with the labeling index of PCNA (P<0.001) in HCC and with aggressive tumor phenotypes, such as larger tumor size, multiple tumors, bilobar involvement, poor tumor cell differentiation, advanced stage and macrovascular invasion (P<0.05). In addition, HCC patients with FOXM1-positive tumors had a poorer recurrence-free and overall survival after hepatectomy than those with FOXM1-negative tumors. Multivariate Cox regression analysis demonstrated that FOXM1 expression was an independent predictor of unfavorable outcome (P<0.05). The data from the current study suggest that FOXM1 may play an important role in HCC progression and could be further evaluated as a prognostic biomarker and potential therapeutic target.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/metabolismo , Fatores de Transcrição Forkhead/biossíntese , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/patologia , Feminino , Proteína Forkhead Box M1 , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise Serial de TecidosRESUMO
In the title compound, C(18)H(14)N(4)O(2)·C(8)H(6)O(4), both types of mol-ecule lie on inversion centers. In the N,N'-bis-(pyridin-3-yl)terephthalamide mol-ecule, the pyridine ring forms a dihedral angle of 11.33â (9)° with the central benzene ring. In the crystal, N-Hâ¯O and O-Hâ¯N hydrogen bonds connect the components into a three-dimensional network.
RESUMO
Two novel Ru(II) complexes [Ru(bpy)(2)(pyip)](2+)1 and [Ru(phen)(2)(pyip)](2+)2 (bpy=2,2'-bipyridine; phen=1,10-phenanthroline; pyip=2-(pyridine-2-yl)imidazo-[4,5-f][1,10]-phenanthroline), have been synthesized and characterized by elemental analysis, ES-MS, (1)H NMR, UV-Vis. The DNA-binding behaviors of both complexes were studied by spectroscopic methods and viscosity measurements. The results indicate that the two complexes can bind to CT-DNA in an intercalative mode, and also show that these two Ru(II) complexes can promote the photocleavage of pBR322 DNA. In addition, In the presence of Co(2+), the emission of DNA-[Ru(L)(2)pyip](2+) can be quenched, which exhibited the DNA "light switch" properties.
Assuntos
DNA/química , Luz , Fenantrolinas/química , Rutênio/química , DNA/metabolismo , Substâncias Intercalantes/química , Estrutura Molecular , Fenantrolinas/metabolismo , Rutênio/metabolismoRESUMO
A monolayer of Nile Blue (NB) has been covalently immobilized on the self-assembled thiol-monolayer modified gold electrode. Cyclic voltammograms indicated a stable and reverse redox process of NB bonded on the electrode surface. The mechanisms of redox process coupling with proton transfer were proposed. The NB-modified electrode showed excellent electrocatalytic activity toward Nicotinamide adenine dinucleotide (NADH) oxidation and horseradish peroxidase (HRP) reduction. A hydrogen peroxide biosensor based on NB as a mediator has been demonstrated.