RESUMO
4,5-Dihydroisoxazoles continue to attract considerable interest due to their wide spread biological activities. Here, we identify an efficient protocol for the preparation of 4,5-dihydroisoxazoles (2-isaxazolines) (4a-g) from quinolinyl chalcones. The nucleolytic activities of synthesized compounds were investigated by agarose gel electrophoresis. All these compounds were showed the remarkable DNA cleavage activity (concentration dependent) with pUC19 DNA at 365nm UV light. The DNA cleavage activity was significantly enhanced by the presence of iminyl and carboxy radicals of DIQ.
Assuntos
Clivagem do DNA/efeitos dos fármacos , Clivagem do DNA/efeitos da radiação , Isoxazóis/farmacologia , Processos Fotoquímicos , Fármacos Fotossensibilizantes/farmacologia , Quinolinas/farmacologia , Isoxazóis/síntese química , Isoxazóis/química , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Plasmídeos/efeitos dos fármacos , Plasmídeos/efeitos da radiação , Quinolinas/síntese química , Quinolinas/química , Quinolinas/efeitos da radiação , Relação Estrutura-Atividade , Raios UltravioletaRESUMO
New 2-chloro-3-formyl quinoline oxime esters were synthesized by the reaction of 2-chloro-3-formyl quinoline oximes with various benzoyl chlorides in the presence of triethyl amine and dichloromethane at 0°C. The DNA photo cleavage studies of some new oxime esters were investigated by neutral agarose gel electrophoresis at different concentrations (40µM and 80µM). Analysis of the cleavage products in agarose gel indicated that few of quinoline oxime esters (3d-i) converted into supercoiled pUC19 plasmid DNA to its nicked or linear form.
Assuntos
DNA/efeitos dos fármacos , Ésteres/farmacologia , Oximas/farmacologia , Quinolinas/farmacologia , Clivagem do DNA/efeitos dos fármacos , Clivagem do DNA/efeitos da radiação , Relação Dose-Resposta a Droga , Ésteres/síntese química , Ésteres/química , Estrutura Molecular , Oximas/síntese química , Oximas/química , Quinolinas/síntese química , Quinolinas/química , Relação Estrutura-Atividade , Raios UltravioletaRESUMO
In the present investigation, a Schiff base N'1,N'3-bis[(E)-(5-bromo-2-hydroxyphenyl)methylidene]benzene-1,3-dicarbohydrazide and its metal complexes have been synthesized and characterized. The DNA-binding studies were performed using absorption spectroscopy, emission spectra, viscosity measurements and thermal denatuaration studies. The experimental evidence indicated that, the Co(II), Ni(II) and Cu(II) complexes interact with calf thymus DNA through intercalation with an intrinsic binding constant Kb of 2.6×10(4) M(-1), 5.7×10(4) M(-1) and 4.5×10(4) M(-1), respectively and they exhibited potent photodamage abilities on pUC19 DNA, through singlet oxygen generation with quantum yields of 0.32, 0.27 and 0.30 respectively. The cytotoxic activity of the complexes resulted that they act as a potent photosensitizers for photochemical reactions.
Assuntos
Antineoplásicos/farmacologia , Cobalto/farmacologia , Complexos de Coordenação/farmacologia , Cobre/farmacologia , Níquel/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Animais , Antineoplásicos/química , Bovinos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cobalto/química , Complexos de Coordenação/química , Cobre/química , DNA/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Níquel/química , Fármacos Fotossensibilizantes/química , Bases de Schiff/química , Bases de Schiff/farmacologia , Oxigênio Singlete/metabolismoRESUMO
New metal complexes of the type [M(nih)(L)](PF(6))(n)·xH(2)O and [M(nih)(2)](PF(6))·xH(2)O (where M=Co(III) or Ni(II), L=1,10-phenanthroline (phen)/or 2,2' bipyridine (bpy), nih=2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone, n=2 or 1 and x=3 or 2) have been synthesized and characterized by elemental analysis, magnetic, IR and (1)H NMR spectral data. The electronic and magnetic moment 2.97-3.07 B.M. data infers octahedral geometry for all the complexes. The IR data reveals that Schiff base (nih) form coordination bond with the metal ion through azomethine-nitrogen, phenolic-oxygen and carbonyl-oxygen in a tridentate fashion. In addition, DNA-binding properties of these six metal complexes were investigated using absorption spectroscopy, viscosity measurements and thermal denaturation methods. The results indicated that the nickel(II) complex strongly bind with calf-thymus DNA with intrinsic DNA binding constant K(b) value of 4.9×10(4) M(-1) for (3), 4.2×10(4) M(-1) for (4), presumably via an intercalation mechanism compared to cobalt(III) complex with K(b) value of 4.6×10(4) M(-1) (1) and 4.1×10(4) M(-1) (2). The DNA Photoclevage experiment shows that, the complexes act as effective DNA cleavage agent.
Assuntos
Anti-Infecciosos/química , Cobalto/química , Complexos de Coordenação/química , DNA/metabolismo , Níquel/química , Bases de Schiff/química , Animais , Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Bovinos , Cobalto/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Fungos/efeitos dos fármacos , Humanos , Hidrazonas/síntese química , Hidrazonas/química , Hidrazonas/farmacologia , Micoses/tratamento farmacológico , Naftalenos/síntese química , Naftalenos/química , Naftalenos/farmacologia , Níquel/farmacologia , Fenantrolinas/síntese química , Fenantrolinas/química , Fenantrolinas/farmacologia , Bases de Schiff/síntese química , Bases de Schiff/farmacologiaRESUMO
In the present investigation, a Schiff base N'(1),N'(3)-bis[(Z)-(2-hydroxynapthyl)methylidene]benzene-1,3-dicarbodihydrazide (L1) and its Co(II), Ni(II) and Cu(II) complexes have been synthesized and characterized as novel photosensitizing agents for photodynamic therapy (PDT). The interaction of these complexes with calf thymus DNA (CT DNA) has been explored using absorption, thermal denaturation and viscometric studies. The experimental results revealed that Co(II) and Ni(II) complexes on binding to CT DNA imply a covalent mode, most possibly involving guanine N7 nitrogen of DNA, with an intrinsic binding constant Kb of 4.5×10(4)M(-1) and 4.2×10(4)M(-1), respectively. However, interestingly, the Cu(II) complex is involved in the surface binding to minor groove via phosphate backbone of DNA double helix with an intrinsic binding constant Kb of 5.7×10(4)M(-1). The Co(II), Ni(II) and Cu(II) complexes are active in cleaving supercoiled (SC) pUC19 DNA on photoexposure to UV-visible light of 365nm, through (1)O2 generation with quantum yields of 0.28, 0.25 and 0.30, respectively. Further, these complexes are cytotoxic in A549 lung cancer cells, showing an enhancement of cytotoxicity upon light irradiation.