RESUMO
Reactive oxygen species have been implicated in several diseases, particularly in ischemia-reperfusion injury. Quercetin 3-O-methyl ether has been reported to show potent antioxidant and neuroprotective activity against neuronal damage induced by reactive oxygen species. Several aminoethyl-substituted derivatives of quercetin 3-O-methyl ether have been synthesized to increase water solubility while retaining antioxidant and neuroprotective activity. Among such derivatives, compound 3a shows potent and well-balanced antioxidant activity in three types of cell-free assay systems and has in vivo neuroprotective effects on transient focal ischemic injury induced by the occlusion of the middle cerebral artery in rats.
Assuntos
Antioxidantes/síntese química , Fármacos Neuroprotetores/síntese química , Quercetina/análogos & derivados , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/tratamento farmacológico , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Quercetina/química , Quercetina/farmacologia , Quercetina/uso terapêutico , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-AtividadeRESUMO
Arvelexin is one of major constituents of Brassica rapa that exerts anti-inflammatory activities. Several indolyl-3-acetonitrile derivatives were synthesized as arvelexin analogs and evaluated for their abilities to inhibit NO and PGE2 productions in LPS-induced RAW 264.7 cells. Of the indolyl-3-acetonitriles synthesized, compound 2k, which possesses a hydroxyl group at C-7 position of the indole ring and an N-methyl substituent, more potently inhibited NO and PGE2 productions and was less cytotoxic than arvelexin on macrophage cells.