RESUMEN
In recent years, great interest has been focused on gold(III) complexes as cytotoxic and antitumor drugs. Recent studies demonstrated that simple bidentate or polydentate ligands containing nitrogen donor atoms may offer sufficient redox stabilization to produce viable Au(III) anticancer drug targets under physiologic conditions. So, we have synthesized square planer Au(III) complexes of type [Au(A(n))Clx]·Cly and characterized them using UV-Vis absorption, C, H, N elemental analysis, FT-IR, LC-MS, (1)H and (13)C NMR spectroscopy. These compounds manifested significant cytotoxic properties in vitro for brine shrimp lethality bioassay. The metal complexes were screened for series of DNA binding activity using UV-Vis absorption titration, hydrodynamic measurement and thermal DNA denaturation study. The nucleolytic activity was performed on plasmid pUC19 DNA. The Michaelis-Menten kinetic studies were performed to evaluate rate of enhancement in metal complexes mediated DNA cleavage over the non-catalyzed DNA cleavage.
Asunto(s)
Citotoxinas/química , Citotoxinas/farmacología , División del ADN/efectos de los fármacos , ADN/metabolismo , Compuestos Orgánicos de Oro/química , Compuestos Orgánicos de Oro/farmacología , Animales , Artemia , Citotoxinas/síntesis química , ADN/química , Peces , Desnaturalización de Ácido Nucleico/efectos de los fármacos , Compuestos Orgánicos de Oro/síntesis química , Pruebas de ToxicidadRESUMEN
Five new copper(II) complexes of type [Cu(erx)(L)Cl] (erx, enrofloxacin; thiophene-2-carbaldehyde (L(1) ); pyridine-2-carbaldehyde (L(2) ); 2,2'-dipyridylamine (L(3) ); 4,5-diazafluoren-9-one (L(4) ); bis(3,5-dimethyl-1-pyrazolyl)methane (L(5) )) have been synthesized and characterized by elemental analysis, reflectance, IR, and FAB-MS. Complexes have been investigated for their interaction with calf thymus (CT) DNA utilizing the absorption-titration method, viscometric and DNA thermal denaturation studies. The cleavage reaction on pUC19 DNA has been monitored by agarose gel electrophoresis. The results indicated that the Cu(II) complexes can more effectively promote the cleavage of plasmid DNA at physiological pH and superoxide dismutase. The (SOD) activity of the complexes has been evaluated by the nitroblue tetrazolium assay, and the complexes catalyzed the dismutation of superoxide at pHâ 7.8 with IC(50) values of 0.35-1.25â µM. The complexes have also been screened for their antibacterial activity against five pathogenic bacteria.
Asunto(s)
Materiales Biomiméticos/metabolismo , Complejos de Coordinación/metabolismo , Cobre/química , ADN/metabolismo , Fluoroquinolonas/química , Animales , Antibacterianos/química , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Materiales Biomiméticos/química , Dominio Catalítico , Bovinos , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , División del ADN/efectos de los fármacos , Enrofloxacina , Concentración de Iones de Hidrógeno , Pruebas de Sensibilidad Microbiana , Plásmidos/metabolismo , Superóxido Dismutasa/metabolismo , Superóxidos/química , Superóxidos/metabolismoRESUMEN
The neutral mononuclear copper complexes with the quinolone antibacterial drug ciprofloxacin and bipyridine derivatives have been synthesized and characterized. Complexes were screened for their antibacterial activity against three Gram((-)) and two Gram((+)) bacteria, and study suggests inhibition of gyrase activity by metal complexes as the possible mechanism. The nucleolytic activity of adducts was carried out on double stranded pUC19 DNA using gel electrophoresis in the presence of radical scavenging agents that suggest hydrolytic cleavage mechanism for plasmid DNA.
Asunto(s)
División del ADN/efectos de los fármacos , ADN-Topoisomerasas/metabolismo , ADN/metabolismo , Electrólisis , Compuestos Organometálicos/metabolismo , Compuestos Organometálicos/farmacología , 2,2'-Dipiridil/química , Antibacterianos/síntesis química , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Cobre/química , ADN/química , Hidrólisis , Fenómenos Magnéticos , Desnaturalización de Ácido Nucleico , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Quinolonas/química , Superóxido Dismutasa/metabolismo , Temperatura , Termodinámica , Inhibidores de Topoisomerasa II , Inhibidores de Topoisomerasa/síntesis química , Inhibidores de Topoisomerasa/química , Inhibidores de Topoisomerasa/metabolismo , Inhibidores de Topoisomerasa/farmacología , ViscosidadRESUMEN
The interaction of small molecules with DNA has attracted a great deal of attention. Mixed ligand copper(II) complexes of type [Cu(cpf)(Ln)Cl] [cpf = ciprofloxacin, Ln = phenanthroline derivatives] were synthesized and characterized by elemental analysis, reflectance, IR and mass spectra. Viscosity measurements, absorption titration and DNA melting temperature studies were employed to determine the mode of binding of complexes with DNA. DNA cleavage study showed better cleaving ability of the complexes compare to metal salts and standard drug. The SOD mimic study showed IC50 value of complexes in the range of 0.95 to 1.75 µM. Antibacterial activity was assayed against selective Gram(-ve) and Gram(+ve) microorganisms.
RESUMEN
The bidentate ligands and Pd(II) complexes have been synthesized and characterized using elemental analysis (C, H, N), (1)H NMR, (13)C NMR, electronic spectra, FT-IR and FAB mass spectroscopy. The binding of palladium complexes with calf thymus DNA (CT DNA) has been explored using absorption titration, DNA melting temperature and viscosity measurements. The cleavage reaction on pUC19 DNA has been monitored by agarose gel electrophoresis. The results suggest that complexes can bind to DNA by intercalative modes and exhibit nuclease activities in which supercoil form is converted to open circular form. The antibacterial activity of ligands and complexes has been performed against three Gram(-ve) and two Gram(+ve) microorganisms and the study indicates that all the complexes show better microbial inhibition activity than ligands and palladium salt.
Asunto(s)
Antibacterianos/farmacología , Complejos de Coordinación/metabolismo , Complejos de Coordinación/farmacología , Ácidos Nucleicos/metabolismo , Paladio/metabolismo , Paladio/farmacología , Absorción/efectos de los fármacos , Animales , Antibacterianos/metabolismo , Bacterias/efectos de los fármacos , Bovinos , ADN/metabolismo , ADN/farmacología , División del ADN/efectos de los fármacos , Electrones , Cinética , Ligandos , Magnetismo , Espectrometría de Masas , Pruebas de Sensibilidad Microbiana , Desnaturalización de Ácido Nucleico/efectos de los fármacos , Plásmidos/metabolismo , Espectrofotometría Infrarroja , Temperatura , Volumetría , Viscosidad/efectos de los fármacosRESUMEN
Novel metal complexes of the second-generation quinolone antibacterial agent enrofloxacin with copper(II) and neutral bidentate ligands have been prepared and characterized with elemental analysis reflectance, IR and mass spectroscopy. Complexes have been screened for their in-vitro antibacterial activity against two Gram(+ve) Staphylococcus aureus, Bacillus subtilis, and three Gram((-ve)) Serratia marcescens, Escherichia coli and Pseudomonas aeruginosa organisms using the double dilution technique. The binding of this complex with CT-DNA has been investigated by absorption titration, salt effect and viscosity measurements. Binding constant is ranging from 1.3×10(4)-3.7×10(4). The cleavage ability of complexes has been assessed by gel electrophoresis using pUC19 DNA. The catalytic activity of the copper(II) complexes towards the superoxide anion (O2.-) dismutation was assayed by their ability to inhibit the reduction of nitroblue tetrazolium (NBT).