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 three Ru(II) complexes of [Ru(phen)(2)dppca](2+) (1) [Ru(bpy)(2)dppca](2+) (2) and [Ru(dmb)(2)dppca](2+) (3) (where phen = 1,10 phenanthroline, bpy = 2,2-bipyridine, dmb = 2 ,2-dimethyl 2',2'-bipyridine and polypyridyl ligand containing a single carboxylate functionality dppca ligand (dipyridophenazine-11-carboxylic acid) have been synthesized and characterized. These complexes have been shown to act as promising calf thymus DNA intercalators and a new class of DNA light switches, as evidenced by UV-visible and luminescence titrations with Co(2+) and EDTA, steady-state emission quenching by [Fe(CN)(6)](4-) and KI, DNA competitive binding with ethidium bromide, viscosity measurements, and DNA melting experiments. The results suggest that 1, 2, and 3 complexes bind to CT-DNA through intercalation and follows the order 1 > 2 > 3. Under irradiation at 365 nm, the three complexes have also been found to promote the photocleavage of plasmid pBR322 DNA.
