RESUMO
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
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) 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
A novel polypyridyl ligand CNPFIP (CNPFIP=2-(5(4-chloro-2-nitrophenyl)furan-2-yl)-1H-imidazo[4,5f][1,10]phenanthroline) and its mononuclear Ru(II) polypyridyl complexes of [Ru(phen)2CNPFIP](2+)(1) (phen=1,10-phenanthroline), [Ru(bpy)2CNPFIP](2+)(2) (bpy=2,2'-bipyridine), and [Ru(dmb)2CNPFIP](2+)(3) (dmb=4,4'-dimethyl-2,2'-bipyridine) have been synthesized successfully and characterized thoroughly by elemental analysis, UV/Vis, IR, NMR, and ESI-MS. The interaction of the Ru(II) complexes with calf thymus DNA (CT-DNA) was investigated by absorption titration, fluorescence, viscosity measurements. The experimental results suggest that three complexes bind to CT-DNA through an intercalative mode and the DNA-binding affinity of complex 1 is greater than that of complexes 2 and 3. The photocleavage of plasmid pBR322 DNA by ruthenium complexes 1, 2, and 3 was investigated. We have also tested three complexes for their antimicrobial activity against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacteria. The in vitro cytotoxicity of these complexes was evaluated by MTT assay, and complex 1 shows higher cytotoxicity than 2 and 3 on HeLa cells. The induced apoptosis and cell cycle arrest of HeLa cells were investigated by flow cytometry for 24h. The molecular docking of ruthenium complexes 1, 2, and 3 with the active site pocket residues of human DNA TOP1 was performed using LibDock.