RESUMEN
OBJECTIVES: To synthesize and characterize 4-(substituted benzylidene)-2-(substituted phenyl)oxazol-5(4H)-one derivatives (E1-E10), and evaluate them for antioxidant activity. MATERIALS AND METHODS: Required oxazole-5(4H)-one derivatives were synthesized in two steps to obtain novel hippuric acid derivatives (7-13); glycine and acylated appropriate benzoic acid derivatives were used and then, final compounds were obtained with condensation of 7-13 with appropriate benzaldehydes (E1-E10). These products were purified by column chromatography using ethyl acetate/n-hexane as eluent. All the compounds were unequivocally characterized using the combination of 1H and 13C-nuclear magnetic resonance, mass spectrometry (ESI-MS), and elemental analysis. The inhibition of lipid peroxidation and its effects on hepatic cytochrome P450-dependent ethoxyresorufin-O-deethylase (EROD) enzyme were determined in rats in vitro. RESULTS: The most active analogue on the microsomal EROD activity was E3 which inhibited the microsomal EROD activity (89%) and was similarly better than that of the specific inhibitor caffeine (85%) at 10-3 M concentration. CONCLUSION: The findings of this study indicate that the synthesized compounds, such as E3, display significant antioxidant activity.
RESUMEN
In this study, some novel 5-[[2-(phenyl/p-chlorophenyl)-benzimidazol-1-yl]-methyl]-N-substituted phenyl-1,3,4-oxadiazol-2-amine derivatives (28-45) with an oxadiazole ring were synthesized. The antioxidant properties and radical scavenging activities of the compounds were investigated employing various in vitro systems: hepatic microsomal NADPH-dependent inhibition of lipid peroxidation levels, scavenging of DPPH free radicals, and inhibition of microsomal ethoxyresorufin O-deethylase activity (EROD). Compounds 34 and 41 were found to be good scavengers of DPPH radicals (76% and 84%) when compared to BHT (90%). Almost all of the compounds examined were found to possess a good inhibitor effect on the microsomal EROD activity. Moreover, 32 and 41 were more active analogs (97% and 98%) on the microsomal EROD activity than caffeine (85%).
Asunto(s)
Aminas/farmacología , Antioxidantes/farmacología , Oxadiazoles/farmacología , Aminas/síntesis química , Aminas/química , Animales , Antioxidantes/síntesis química , Antioxidantes/química , Citocromo P-450 CYP1A1/antagonistas & inhibidores , Citocromo P-450 CYP1A1/metabolismo , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Radicales Libres/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Oxadiazoles/síntesis química , Oxadiazoles/química , Ratas , Ratas Wistar , Relación Estructura-ActividadRESUMEN
In this study, we prepared some new oxadiazolyl benzimidazole derivatives and investigated their antioxidant properties by determination of microsomal NADPH-dependent inhibition of lipid peroxidation levels (LP assay) and microsomal ethoxyresorufin O-deethylase activity (EROD assay). Some of these compounds 20, 23 had slightly inhibitory effects (28%) on the lipid peroxidation levels at 10(-3 )M concentration lower than standard BHT (65%). 5-[2-(Phenyl)-benzimidazol-1-yl-methyl]-2-mercapto-[1,3,4]-oxadiazole 16 was found to be more active than caffeine on the ethoxyresorufin O-deethylase activity with an IC(50 )value of 2.0 6 10(-4 )M.