RESUMEN
A new class of Cu(II) and Co(II) complexes of azo-containing Schiff base of the type [Cu(L1)2] and [Co(L1)2], where L1=4-[(E)-{2-hydroxy-3-[(E)-(4-bromophenyl)diazenyl]benzylidene}amino]benzoic acid have been synthesized and characterized. Extension of conjugation and the presence of free carboxylic acid group of the ligand L1 increased the wavelength of the complexes from visible region to the near IR region (620-850 nm). The Cu(II) and Co(II) complexes interacted with CT-DNA via intercalative mode with the respective Kb value of 3.2×10(4) M(-1) and 2.9×10(4) M(-1) and acted as proficient photocleavers of SC pUC19 DNA in UV-A light, forming (1)O2 as the reactive oxygen species with the quantum yield of 0.38 and 0.36, respectively. Furthermore, the Cu(II) and Co(II) complexes showed photocytotoxicity toward two selected tumor cell lines MCF-7 and A549 by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) method, and the Cu(II) complex exhibits higher photocytotoxicity than Co(II) complex against each of the selected cell lines, this result is identical with their DNA binding ability order.
Asunto(s)
Cobalto/farmacología , Cobre/farmacología , División del ADN/efectos de los fármacos , ADN/metabolismo , Fármacos Fotosensibilizantes/farmacología , Bases de Schiff/farmacología , Animales , Bovinos , Electrones , Electroforesis en Gel de Agar , Humanos , Concentración 50 Inhibidora , Células MCF-7 , Espectrometría de Masas , Desnaturalización de Ácido Nucleico/efectos de los fármacos , Espectroscopía de Protones por Resonancia Magnética , Oxígeno Singlete/química , Solubilidad , Espectrofotometría Infrarroja , Espectrofotometría Ultravioleta , ViscosidadRESUMEN
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.
Asunto(s)
Antineoplásicos/farmacología , Complejos de Coordinación/farmacología , Fármacos Fotosensibilizantes/farmacología , Bases de Schiff/farmacología , Oxígeno Singlete/metabolismo , Absorción , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Benzofuranos/química , Bovinos , Muerte Celular/efectos de los fármacos , Muerte Celular/efectos de la radiación , Línea Celular Tumoral , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , ADN/metabolismo , División del ADN/efectos de los fármacos , Espectroscopía de Resonancia por Spin del Electrón , Electroforesis en Gel de Agar , Humanos , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Desnaturalización de Ácido Nucleico/efectos de los fármacos , Desnaturalización de Ácido Nucleico/efectos de la radiación , Plásmidos/metabolismo , Bases de Schiff/síntesis química , Bases de Schiff/química , Oxígeno Singlete/química , Espectrofotometría Infrarroja , Superóxidos/metabolismo , Temperatura , Termodinámica , Rayos Ultravioleta , ViscosidadRESUMEN
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.
Asunto(s)
Antineoplásicos/farmacología , Cobalto/farmacología , Complejos de Coordinación/farmacología , Cobre/farmacología , Níquel/farmacología , Fármacos Fotosensibilizantes/farmacología , Animales , Antineoplásicos/química , Bovinos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cobalto/química , Complejos de Coordinación/química , Cobre/química , ADN/metabolismo , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Níquel/química , Fármacos Fotosensibilizantes/química , Bases de Schiff/química , Bases de Schiff/farmacología , Oxígeno Singlete/metabolismoRESUMEN
A new tetra-aza macrocyclic ligand, L (C(24)H(16)N(12)O(2)S(4)) and its complexes of type, [MLCl(2)] and [CuL]Cl(2) (where M=Ni(II), Co(II); L=N,N'-(benzene-1,3-diyldi-1,3,4-thiadiazole-5,2-diyl)bis{2-[(5-benzene-1,3-diyl-1,3,4-thiadiazol-2-yl)amino]acetamide}) were synthesized and characterized by the spectral and analytical techniques. An octahedral geometry has been proposed for Ni(II) and Co(II) complexes while Cu(II) complex exhibit a square planar geometry. All the synthesized metal complexes were screened for their in vitro antimicrobial activity against selected species of pathogenic bacteria and fungi. The binding property of the complexes with CT-DNA was studied by absorption spectral analysis, followed by viscosity measurement and thermal denaturation studies. The photo induced cleavage studies revealed that the complexes possess photonuclease property against pUC19 DNA under UV-visible irradiation.