RESUMO
A series hydroxycinnamic and gallic acids and their derivatives were studied with the aim of evaluating their in vitro antioxidant properties both in homogeneous and in cellular systems. It was concluded from the oxygen radical absorbance capacity-fluorescein (ORAC-FL), 1,1-diphenyl-2-picrylhydrazyl (DPPH), and cyclic voltammetry data that some compounds exhibit remarkable antioxidant properties. In general, in homogeneous media (DPPH assay), galloyl-based cinnamic and benzoic systems (compounds 7-11) were the most active, exhibiting the lowest oxidation potentials in both dimethyl sulfoxide (DMSO) and phosphate buffer. Yet, p-coumaric acid and its derivatives (compounds 1-3) disclosed the highest scavenging activity toward peroxyl radicals (ORAC-FL assay). Interesting structure-property- activity relationships between ORAC-FL, or DPPH radical, and redox potentials have been attained, showing that the latter parameter can be a valuable antioxidant measure. It was evidenced that redox potentials are related to the structural features of cinnamic and benzoic systems and that their activities are also dependent on the radical generated in the assay. Electron spin resonance data of the phenoxyl radicals generated both in DMSO and phosphate buffer support the assumption that radical stability is related to the type of phenolic system. Galloyl-based cinnamic and benzoic ester-type systems (compounds 9 and 11) were the most active and effective compounds in cell-based assays (51.13 ± 1.27% and 54.90 ± 3.65%, respectively). In cellular systems, hydroxycinnamic and hydroxybenzoic systems operate based on their intrinsic antioxidant outline and lipophilic properties, so the balance between these two properties is considered of the utmost importance to ensure their performance in the prevention or minimization of the effects due to free radical overproduction.
Assuntos
Antioxidantes/metabolismo , Ácidos Cumáricos/metabolismo , Técnicas Eletroquímicas , Hidroxibenzoatos/metabolismo , Animais , Antioxidantes/química , Linhagem Celular , Ácidos Cumáricos/química , Espectroscopia de Ressonância de Spin Eletrônica , Hidroxibenzoatos/química , Camundongos , Estrutura MolecularRESUMO
The study of antioxidants and radicals has always been a complex task due to the special characteristics of these species such as reactions at low concentrations and short half-lives. Current techniques do not always produce good results and in some cases they can only be applied in chemical models. From this point of view, the development of electron spin resonance (ESR) has allowed the study of the antioxidant capacity of a wide variety of compounds and the detection of radicals in the reactions in which they are involved. The DPPH technique allows only the study of antioxidants in pure chemical models. The ORAC-ESR assay, based on the spin trapping technique, emerges as an interesting tool for identifying and quantifying the antioxidant capacity of different samples. Furthermore, the spin trapping technique allows us to characterize radicals in in vivo/ex vivo models. The present review discusses the current available techniques associated with ESR for the study of antioxidants and radical species.
Assuntos
Antioxidantes/análise , Espectroscopia de Ressonância de Spin Eletrônica , Radicais Livres/análise , Animais , Antioxidantes/farmacocinética , Compostos de Bifenilo/química , Óxidos N-Cíclicos/química , Radicais Livres/metabolismo , Meia-Vida , Humanos , Picratos/química , Detecção de SpinRESUMO
The electron spin resonance (ESR) spectra of free radicals obtained by electrolytic reduction of triazolopyridyl pyridyl ketones and dipyridyl ketones derivatives were measured in dimethylsulfoxide (DMSO). The hyperfine patterns indicate that the spin density delocalization is dependent of the rings presented in the molecule. The electrochemistry of these compounds was characterized using cyclic voltammetry, in DMSO as solvent. When one carbonyl is present in the molecule one step in the reduction mechanism was observed while two carbonyl are present two steps were detected. The first wave was assigned to the generation of the correspondent free radical species, and the second wave was assigned to the dianion derivatives. The phase-solubility measurements indicated an interaction between molecules selected and cyclodextrins in water. These inclusion complexes are 1:1 with betaCD, and HP-betaCD. The values of Ks showed a different kind of complexes depending on which rings are included. AM1 and DFT calculations were performed to obtain the optimized geometries, theoretical hyperfine constants, and spin distributions, respectively. The theoretical results are in complete agreement with the experimental ones.
Assuntos
Compostos Azo/química , Ciclodextrinas/química , Cetonas/química , Piridinas/química , Eletroquímica , Espectroscopia de Ressonância de Spin Eletrônica , Estrutura Molecular , SolubilidadeRESUMO
The synthesis and evaluation as hypoxic selective cytotoxins of new derivatives of 2-amino or 2-hydroxyphenazine 5,10-dioxide are described. The compounds were developed as structural analogs of other bioreductive compounds and its in vitro cytotoxicities on V79 cells under hypoxic and aerobic conditions were determined. To gain insight into its mechanism of action electrochemical behavior, interaction with DNA experiments and QSAR studies were performed.
Assuntos
Citotoxinas/química , Citotoxinas/farmacologia , Fenazinas/química , Fenazinas/toxicidade , Relação Quantitativa Estrutura-Atividade , Animais , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular , Cricetinae , Citotoxinas/síntese química , DNA/química , Eletroquímica , Estrutura Molecular , Fenazinas/síntese química , Análise EspectralRESUMO
Cyclic voltammetry and electron spin resonance (ESR) techniques were used in the investigation of several potential antiprotozoal thiosemicarbazones nitrofurane derivatives. A self-protonation process involving the protonation of the nitro group due to the presence of an acidic proton in the thiosemicarbazone moiety was observed in the first step of a CEE(rev) reduction mechanism of these derivatives. ESR spectra of the free radicals obtained by electrolytic reduction were characterized and analyzed. AM1 methodology was used to obtain the optimized geometries and UB3LYP calculations were performed to obtain the theoretical hyperfine coupling constants. The theoretical study exhibited an unusual assignment of the spin densities showing a free radical centered in the thiosemicarbazone moiety rather than the nitro which are in agreement with the experimental hyperfine pattern.
Assuntos
Antiprotozoários/química , Nitrofuranos/química , Tiossemicarbazonas/química , Eletroquímica , Espectroscopia de Ressonância de Spin Eletrônica , Estrutura Molecular , Nitrogênio/química , OxirreduçãoRESUMO
The ESR spectra of radicals obtained by electrolytic reduction of 2-acylpyridines and 6,6'-diacyl-2,2'-bipyridines were measured in dimethylsulfoxide (DMSO) and analyzed by quantum chemical calculations. The electrochemistry of these compounds was characterized using cyclic voltammetry, in DMSO solvent. The results showed a two step reduction mechanism, first wave was assigned to the generation of the correspondent free radical species, and the second wave was assigned to the dianion derivatives. AM1 and DFT calculations were performed to obtain the optimized geometries, theoretical hyperfine constants, and spin distributions, respectively. The theoretical results are in complete agreement with the experimental ones.
Assuntos
Piridinas/química , Acilação , Ânions/química , Dimetil Sulfóxido/química , Eletroquímica , Eletrodos , Espectroscopia de Ressonância de Spin Eletrônica , Radicais Livres/química , Estrutura MolecularRESUMO
PURPOSE: To study the reactivity of C4-substituted 1,4-dihydropyridines (1,4-DHP), with either secondary or tertiary nitrogen in the dihydropyridine ring, toward SIN-1-derived peroxynitrite in aqueous media at pH 7.4. METHODS: Reactivity was followed by changes in the absorptivity of the UV-Vis bands corresponding to 1,4-DHP. Gas Chromatography/ Mass Spectrometer (GC-MS) and Electron Paramagnetic Resonance (EPR) spin trap techniques were used to characterize the final product and the intermediates of the reaction, respectively. RESULTS: 1,4-DHPs significantly reacted toward peroxynitrite at varied rates, according to the calculated kinetic rate constants. By EPR spectroscopy, a carbon-centered radical from the 1,4-DHP was intercepted with N-tert-butylamine-alpha-phenylnitrone (PBN), as the intermediate for the reaction with peroxynitrite. Likewise, the oxidized derivative (i.e., the pyridine) was identified as the final product of the reaction by GC-MS. By using the technique of deuterium kinetic isotope effect, the participation of the hydrogen of the 1-position on the 1,4-DHP ring was shown not to be the rate-limiting step of the reaction. CONCLUSIONS: The direct participation of the 1,4-DHP derivatives in the quenching of SIN-1-derived peroxynitrite has been demonstrated. Kinetic rate constant of tested 1,4-DHP toward peroxynitrite showed a direct relationship with the oxidation peak potential values; that is, compounds reacting faster were more easily oxidized.
Assuntos
Di-Hidropiridinas/química , Molsidomina/análogos & derivados , Molsidomina/química , Ácido Peroxinitroso/química , Deutério , Espectroscopia de Ressonância de Spin Eletrônica , Cromatografia Gasosa-Espectrometria de Massas , Indicadores e Reagentes , Cinética , Espectroscopia de Ressonância Magnética , Oxirredução , Soluções , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
The electron spin resonance (ESR) spectra of free radicals obtained by electrolytic or microsomal reduction of several potential antiprotozoal 1,2,5-oxadiazoles were characterized and analyzed. Ab initio molecular orbital calculations were performed to obtain the optimized geometries and the theoretical hyperfine constant was carried out using ZINDO semiempirical methodology. Density functional theory was used to rationalize the reduction potentials of these compounds.
Assuntos
Antiprotozoários/farmacologia , Eletroquímica/métodos , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Radicais Livres , Oxidiazóis/análise , Microssomos , Modelos Químicos , Oxidiazóis/químicaRESUMO
Several new 1,2,5-oxadiazole N-oxide derivatives and some deoxygenated analogues were synthesized to be tested as potential selective hypoxic cell cytotoxins. Compounds prepared were designed in order to gain insight into the mechanism of action of this kind of cytotoxin. Compounds were tested in oxia and hypoxia and they proved to be non-selective. 3-Cyano-N(2)-oxide-4-phenyl-1,2,5-oxadiazole showed the best cytotoxic activity in oxia. The cytotoxicity observed for these derivatives could be explained in terms of the electronic characteristics of the 1,2,5-oxadiazole substituents. Electrochemical and ESR studies were performed on the more cytotoxic derivative.
Assuntos
Antineoplásicos/síntese química , Oxidiazóis/química , Oxidiazóis/síntese química , Aerobiose/fisiologia , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Hipóxia Celular/fisiologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Clonais , Cricetinae , Citotoxinas/farmacologia , Relação Estrutura-AtividadeRESUMO
The endogenous dopamine-derived neurotoxin salsolinol was found to decrease survival in the dopaminergic neuronal cell line RCSN-3, derived from adult rat substantia nigra in a concentration-dependent manner (208 microM salsolinol induced a 50% survival decrease). Incubation of RCSN-3 cells with 100 micro;M dicoumarol and salsolinol significantly decreased cell survival by 2.5-fold (P < 0.001), contrasting with a negligible effect on RCHT cells, which exhibited nearly a 5-fold lower nomifensine-insensitive dopamine uptake. The levels of catalase and glutathione peroxidase mRNA were decreased when RCSN-3 cells were treated with 100 microM salsolinol alone or in the presence of 100 microM dicoumarol. In vitro oxidation of salsolinol to o-quinone catalyzed by lactoperoxidase gave the quinone methide and 1,2-dihydro-1-methyl-6,7-isoquinoline diol as final products of salsolinol oxidation as determined by NMR analysis. Evidence of the formation of salsolinol o-semiquinone radical has been provided by ESR studies during one-electron oxidation of salsolinol catalyzed by lactoperoxidase.