RESUMO
A new ligand DBHIP and its two ruthenium(II) complexes [Ru(dmb)(2)(DBHIP)](ClO(4))(2) (1) and [Ru(dmp)(2)(DBHIP)](ClO(4))(2) (2) have been synthesized and characterized. The cytotoxicity of DBHIP and complexes 1 and 2 has been assessed by MTT assay. The apoptosis studies were carried out with acridine orange/ethidium bromide (AO/EB) staining methods. The binding behaviors of these complexes to calf thymus DNA (CT-DNA) were studied by absorption titration, viscosity measurements, thermal denaturation and photoactivated cleavage. The DNA-binding constants of complexes 1 and 2 were determined to be 8.64 +/- 0.16 x 10(4) (s = 1.34) and 2.79 +/- 0.21 x 10(4) (s = 2.17) M(-1). The results suggest that these complexes interact with DNA through intercalative mode. 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 in the DNA cleavage. The experiments on antioxidant activity show that these compounds also exhibit good antioxidant activity against hydroxyl radical (OH*).
Assuntos
Antioxidantes , Apoptose/efeitos dos fármacos , DNA/efeitos dos fármacos , DNA/metabolismo , Fenantrolinas/química , Compostos de Rutênio , Animais , Antioxidantes/síntese química , Antioxidantes/química , Antioxidantes/farmacologia , Bovinos , Linhagem Celular , DNA/química , Clivagem do DNA/efeitos dos fármacos , Ligantes , Estrutura Molecular , Desnaturação de Ácido Nucleico , Compostos de Rutênio/síntese química , Compostos de Rutênio/química , Compostos de Rutênio/farmacologia , ViscosidadeRESUMO
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 Ru(II) 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 (O2(.-)) 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.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , DNA/metabolismo , Neoplasias/tratamento farmacológico , Compostos de Rutênio/química , Compostos de Rutênio/farmacologia , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Modelos Moleculares , Estrutura Molecular , Desnaturação de Ácido Nucleico/efeitos dos fármacos , Fenantrolinas/síntese química , Fenantrolinas/química , Fenantrolinas/farmacologia , Processos Fotoquímicos/efeitos dos fármacos , Compostos de Rutênio/síntese química , Viscosidade/efeitos dos fármacosRESUMO
The title compound, [Ru(C(14)H(12)N(2))(2)(C(18)H(14)N(4))](ClO(4))(2)·2H(2)O, consists of an Ru(II) complex cation, two perchlorate anions and two uncoordinated water mol-ecules. The Ru(II) ion is chelated by a 10,11,12,13-tetra-hydro-dipyrido[3,2-a:2',3'-c]phenazine ligand and two 2,9-dimethyl-1,10-phenanthroline ligands in a distorted octa-hedral geometry. The two uncoord-inated water mol-ecules are disordered over five positions, with an occupancy factor of about 0.4 for each site. A supra-molecular structure is formed by weak π-π inter-actions between neighbouring mol-ecules, with centroid-centroid distances of 3.618â (2) and 3.749â (2)â Å.
RESUMO
Two new ligands, 3-(pyrazin-2-yl)-as-triazino[5,6-f]-5-methoxylisatin (dtmi), 3-(pyrazin-2-yl)-as-triazino[5,6-f]-5-nitroisatin (dtni) and their ruthenium(II) complexes [Ru(phen)2(dtmi)](ClO4)2 (1) and [Ru(phen)2(dtni)](ClO4)2 (2) have been prepared and characterized by elemental analysis, FAB-MS, ES-MS and 1H NMR. The DNA-binding behaviors of complexes have been studied by spectroscopic titration, viscosity measurements, thermal denaturation and circular dichromism (CD). The results indicate that the complexes 1 and 2 interact with calf thymus DNA (CT-DNA) by intercalative mode. The DNA-binding affinity of the complexes 2 is larger than that complex 1 does.
Assuntos
DNA/metabolismo , Substâncias Intercalantes/química , Compostos Organometálicos/química , Fenantrolinas/química , Pirazinas/química , Rutênio/química , Animais , Bovinos , Dicroísmo Circular , DNA/química , Temperatura Alta , Substâncias Intercalantes/metabolismo , Ligantes , Microquímica/métodos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Desnaturação de Ácido Nucleico , Compostos Organometálicos/metabolismo , Fenantrolinas/metabolismo , Pirazinas/metabolismo , Espectrometria de Massas por Ionização por Electrospray , ViscosidadeRESUMO
Linear diaryliodonium salts are widely used as arylating reagents for C-C and C-X bond formation. Meanwhile, synthetic applications of cyclic iodoniums are relatively rare although they offer the opportunity to set up reaction cascades. We demonstrate an atom and step economical three-component reaction involving cyclic diphenyleneiodoniums, alkynes, and boronic acids, resulting in the construction of methylidenefluorenes in a single operation. Our route enables facile access to both symmetrical and unsymmetrical methylidenefluorene derivatives, compounds that have attracted interest due to their optical properties.
Assuntos
Ácidos Borônicos/química , Cobre/química , Fluorenos/síntese química , Oniocompostos/química , Paládio/química , Catálise , Fluorenos/química , Estrutura MolecularRESUMO
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).
Assuntos
DNA/metabolismo , Sequestradores de Radicais Livres/síntese química , Sequestradores de Radicais Livres/metabolismo , Compostos Organometálicos/síntese química , Compostos Organometálicos/metabolismo , Processos Fotoquímicos , Piridinas/química , Rutênio/química , Absorção , Animais , Bovinos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , DNA/química , Elétrons , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/toxicidade , Humanos , Radical Hidroxila/química , Desnaturação de Ácido Nucleico , Compostos Organometálicos/farmacologia , Compostos Organometálicos/toxicidade , Ratos , Análise Espectral , Temperatura de Transição , ViscosidadeRESUMO
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.
Assuntos
DNA/metabolismo , Substâncias Intercalantes/toxicidade , Rutênio/toxicidade , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Substâncias Intercalantes/química , Substâncias Intercalantes/metabolismo , Fenantrolinas/síntese química , Fenantrolinas/química , Fenantrolinas/toxicidade , Rutênio/química , Rutênio/metabolismo , ViscosidadeRESUMO
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.