RESUMO
The octahedral Ru(II) complexes containing the 2(2,6-dimethoxypyridine-3-yl)-1H-imidazo(4,5-f)[1, 10]phenanthroline ligand of type [Ru(N-N)2(L)]2+, where N-N = phen (1,10-phenanthroline) (1), bpy (2,2'-bipyridine) (2), and dmb (4,4'-dimethyl-2,2'-bipyridine) (3); L(dmpip) = (2(2,6-dimethoxypyridine-3-yl)1Himidazo(4,5-f)[1, 10]phenanthroline), have been synthesized and characterized by UV-visible absorption, molar conductivity, elemental analysis, mass, IR, and NMR spectroscopic techniques. The physicochemical properties of the Ru(II) complexes were determined by UV-Vis absorption spectroscopy. The DNA binding studies have been explored by UV-visible absorption, fluorescence titrations, and viscosity measurements. The supercoiled pBR322 DNA cleavage efficiency of Ru(II) complexes 1-3 was investigated. The antimicrobial activity of Ru(II) complexes was done against Gram-positive and Gram-negative microorganisms. The in vitro anticancer activities of all the complexes were investigated by cell viability assay, apoptosis, cellular uptake, mitochondrial membrane potential detection, and semi-quantitative PCR on HeLa cells. The result indicates that the synthesized Ru(II) complexes probably interact with DNA through an intercalation mode of binding with complex 1 having slightly stronger DNA binding affinity and anticancer activity than 2 and 3.
Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , DNA/efeitos dos fármacos , Rutênio/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Bacillus megaterium/efeitos dos fármacos , Bacillus megaterium/crescimento & desenvolvimento , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/crescimento & desenvolvimento , Sítios de Ligação/efeitos dos fármacos , Bovinos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , DNA/química , Dano ao DNA , Relação Dose-Resposta a Droga , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Células HeLa , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Micrococcus luteus/efeitos dos fármacos , Micrococcus luteus/crescimento & desenvolvimento , Estrutura Molecular , Plasmídeos/efeitos dos fármacos , Rutênio/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Relação Estrutura-AtividadeRESUMO
Three new Ru(II) polypyridyl complexes [Ru(phen)2CIIP]2+ (1) {CIIP = 2-(5-Chloro-3a H-Isoindol-3-yl)-1H-Imidazo[4,5-f][1, 10]phenantholine} (phen = 1, 10 phenanthroline), [Ru(bpy)2CIIP]2+ (2) (bpy = 2, 2' bipyridine) and [Ru(dmb)2CIIP]2+ (3) (dmb = 4, 4'-dimethyl 2, 2' bipyridine) were synthesized and characterized by different spectral methods. The DNA-binding behavior of these complexes was investigated by absorption, emission spectroscopic titration and viscosity measurements, indicating that these three complexes bind to CT-DNA in an intercalative mode, but binding affinities of these complexes were different. The DNA-binding constants Kb of complexes 1, 2 and 3 were calculated in the order of 106. All three complexes cleave pBR322 DNA in photoactivated cleavage studies and exhibit good antimicrobial activity. Anticancer activity of these Ru(II) complexes was evaluated in MCF7 cells. Cytotoxicity by MTT assay showed growth inhibition in a dose dependent manner. Cell cycle analysis by flow cytometry data showed an increase in Sub G1 population. Annexin V FITC/PI staining confirms that these complexes cause cell death by the induction of apoptosis.
Assuntos
Antibacterianos/química , Antineoplásicos/química , Complexos de Coordenação/química , Substâncias Intercalantes/química , Isoindóis/química , Fenantrolinas/química , Piridinas/química , Rutênio/química , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Bacillus subtilis/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/farmacologia , DNA/metabolismo , Clivagem do DNA , Escherichia coli/efeitos dos fármacos , Humanos , Substâncias Intercalantes/farmacologia , Isoindóis/farmacologia , Células MCF-7 , Fenantrolinas/farmacologia , Processos Fotoquímicos , Piridinas/farmacologia , TermodinâmicaRESUMO
In this paper a novel ligand debip (2-(4-N,N-diethylbenzenamine)1H-imidazo[4,5-f] [1, 10]phenanthroline) and its Ru(II) polypyridyl complexes [Ru(L)2(debip)]2+, (L = phen (1), bpy (2) and dmb (3)) have been synthesized and characterized by spectroscopic techniques. The DNA binding studies for all these complexes were examined by absorption, emission, quenching studies, viscosity measurements and cyclic voltammetry. The light switching properties of complexes 1-3 have been evaluated. Molecular docking, Density Functional Theory (DFT) and time dependent DFT calculations were performed. The Ru(II) complexes exhibited efficient photocleavage activity against pBR322 DNA upon irradiation and exhibited good antimicrobial activity. Also investigated 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay, lactate dehydrogenase (LDH) release assay and reactive oxygen species (ROS) against selected cancer cell lines (HeLa, PC3, Lancap, MCF-7 and MD-MBA 231).
Assuntos
Complexos de Coordenação/química , DNA/metabolismo , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Piridinas/química , Rutênio/química , Antibacterianos/química , Antibacterianos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Sítios de Ligação , Sobrevivência Celular/efeitos dos fármacos , DNA/química , Escherichia coli/efeitos dos fármacos , Humanos , Substâncias Intercalantes/química , Substâncias Intercalantes/farmacologia , Simulação de Acoplamento Molecular , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Células Tumorais CultivadasRESUMO
Three ruthenium(II) polypyridyl complexes, [Ru(phen)2(mip)](ClO4)2 (1) (phen =1,10-Phenanthroline), [Ru(bpy)2(mip)](ClO4)2 (2) (bpy = 2,2'bipyridyl) and [Ru(dmb)2(mip)](ClO4)2 (3) (dmb = 4, 4'-dimethyl 2, 2'-bipyridine), were synthesized with an intercalative ligand mip (2-morpholino-1H-imidazo[4,5-f][1, 10]phenanthroline) and characterized by 1H, 13C-NMR, IR, UV-vis, mass spectra and elemental analysis. pH effect, ion selectivity (cations, anions) and solvent sensitivity of complexes were studied. The interaction of these complexes with DNA was performed using absorption, emission spectroscopy and viscosity measurements. The experimental results indicated that the two complexes interacted with calf thymus DNA (CT-DNA) by intercalative mode. BSA (Bovine Serum Albumin) protein binding of these complexes was studied by UV-visible and fluorescence techniques. The binding capacity of these complexes was explained theoretically by molecular docking method.
Assuntos
2,2'-Dipiridil/química , DNA/metabolismo , Luminescência , Compostos Organometálicos/química , Compostos Organometálicos/metabolismo , Rutênio/química , Soroalbumina Bovina/metabolismo , Animais , Sítios de Ligação , Bovinos , DNA/química , Concentração de Íons de Hidrogênio , Substâncias Intercalantes/química , Substâncias Intercalantes/metabolismo , Simulação de Acoplamento Molecular , Soroalbumina Bovina/químicaRESUMO
The four novel Ru(II) polypyridyl complexes of [Ru(Hdpa)2dmbip](2+) (1), [Ru(Hdpa)2NO2-dmbip](2+) (2), [Ru(Hdpa)2debip](2+) (3) and [Ru(Hdpa)2OH-debip](2+) (4) where Hdpa = 2,2'-bipyridylamine, dmbip = 2-(4-N,N-dimethylbenzenamine)1H-imidazo[4,5-f][1,10]phenanthroline, debip = 2-(4-N,N-diethylbenzenamine)1H-imidazo[4,5-f][1,10]phenanthroline, NO2-dmbip = NO2-2-(4-N,N-dimethylbenzenamine)1H-imidazo[4,5-f][1,10]phenanthroline, OH-debip = OH-2-(4-N,N-diethylbenzenamine)1H-imidazo[4,5-f][1,10]phenanthroline were synthesized and fully characterized using elemental analysis, Mass, NMR and FT-IR. The DNA binding behavior of all synthesized complexes were investigated by using electronic absorption spectra, emission spectra, cyclic light switch on and off, sensor studies, electrochemical method and viscosity titrations. Docking studies were performed with human DNA TOP1 by using LibDock. Furthermore explore antimicrobial activity, photocleavage and in vitro cytotoxicity assay of four Ru(II) complexes.
Assuntos
Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Clivagem do DNA/efeitos dos fármacos , DNA/metabolismo , Processos Fotoquímicos , Piridinas/química , Rutênio/química , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Técnicas de Química Sintética , Complexos de Coordenação/química , Complexos de Coordenação/metabolismo , DNA/química , DNA Topoisomerases Tipo I/química , DNA Topoisomerases Tipo I/metabolismo , Escherichia coli/efeitos dos fármacos , Células HeLa , Humanos , Substâncias Intercalantes/síntese química , Substâncias Intercalantes/química , Substâncias Intercalantes/metabolismo , Substâncias Intercalantes/farmacologia , Ligantes , Simulação de Acoplamento Molecular , Fenantrolinas/química , Conformação Proteica , Staphylococcus aureus/efeitos dos fármacosRESUMO
The four novel Ru(II) complexes [Ru(phen)2MAFIP](2+) (1) [MAFIP = 2-(5-(methylacetate)furan-2-yl)-1 H-imidazo[4,5-f] [1, 10]phenanthroline, phen = 1,10-Phenanthroline], [Ru(bpy)2MAFIP](2+) (2) (bpy = 2,2'-bipyridine) and [Ru(dmb)2MAFIP](2+) (3) (dmb = 4,4'-dimethyl-2,2'-bipyridine) and [Ru(hdpa)2MAFIP](2+) (4) (hdpa = 2,2-dipyridylamine) have been synthesized and fully characterized via elemental analysis, NMR spectroscopy, EI-MS and FT-IR spectroscopy. In addition, the DNA-binding behaviors of the complexes 1-4 with calf thymus DNA were investigated by UV-Vis absorption, fluorescence studies and viscosity measurement. The DNA-binding experiments showed that the complexes 1-4 interact with CT-DNA through an intercalative mode. BSA protein binding affinity of synthesized complexes was determined by UV/Vis absorption and fluorescence emission titrations. The binding affinity of ruthenium complexes was supported by molecular docking. The photoactivated cleavage of plasmid pBR322 DNA by ruthenium complexes 1-4 was investigated. All the synthesized compounds were tested for antimicrobial activity by using three Gram-negative (Escherichia coli, Salmonella typhi and Pseudomonas aeruginosa) and three Gram-positive (Micrococcus luteus, Bacillus subtilis and Bacillus megaterium) organisms, these results indicated that complex 3 was more activity compared to other complexes against all tested microbial strains while moderate antimicrobial activity profile was noticed for complex 4. The antioxidant activity experiments show that the complexes exhibit moderate antioxidant activity. The cytotoxicity of synthesized complexes on HeLa cell lines has been examined by MTT assay. The apoptosis assay was carried out with Acridine Orange (AO) staining methods and the results indicate that complexes can induce the apoptosis of HeLa cells. The cell cycle arrest investigated by flow cytometry and these results indicate that complexes 1-4 induce the cell cycle arrest at G0/G1 phase.
Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , DNA/química , Compostos Organometálicos/farmacologia , Rutênio/farmacologia , Soroalbumina Bovina/química , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antioxidantes/síntese química , Antioxidantes/química , Sítios de Ligação , Bovinos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Células HeLa , Humanos , Testes de Sensibilidade Microbiana , Conformação Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Fenantrolinas/química , Fenantrolinas/farmacologia , Rutênio/química , Relação Estrutura-AtividadeRESUMO
New three ruthenium (II) polypyridyl complexes [Ru(phen)2mpip](2+)(1) {mpip = 2-(4-morpholinophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline}, (phen = 1,10-Phenanthrolene), [Ru(bpy)2mpip](2+)(2) (bpy = 2,2'bipyridyl), [Ru(dmb)2mpip](2+)(3) (dmb = 4, 4-dimethyl 2, 2'-bipyridine) have been synthesized and characterized by spectral studies IR, UV-vis, (1)H, (13)C-NMR, mass and elemental analysis. The binding properties of these three complexes towards calf-thymus DNA (CT-DNA) have been investigated by UV-Vis spectroscopy, different fluorescence methods and viscosity measurements, indicating that all the complexes bind to CT-DNA by means of intercalation, but with different binding affinities. Sensor effect of ions/solvents and BSA (Bovine Serum Albumin) binding studies of these complexes were also studied. Docking studies also reveals that complexes will bind in between base pairs (Intercalate) of DNA and gives information about the binding strength.