The protective effects of oxyresveratrol imine derivative against hydrogen peroxide-induced cell death in PC12 cells

Oxyresveratrol (2',3,4',5-tetrahydroxystilbene) is a naturally occurring ingredient found in mulberries that shows potential as an antioxidant, anti-inflammatory, and neuroprotective agent. This study was performed to identify materials similar to oxyresveratrol that may have more effective antioxidant properties. We synthesized a stilbene analog referred to as Compound 1 (2',3,4',5-tetramethoxystilbene); a benzamide analog referred to as Compound 2 ((2,4-dimethoxyphenyl)-3,5-dimethoxybenzamide); and three imine analogs referred to as Compound 3 (3,5-dimethoxybenzylidene)-(2,4-dimethoxyphenylamine), Compound 4 ((4-methoxybenzylidene)-(3-methoxyphenyl)amine), and Compound 5 ((4-methoxybenzylidene)phenylamine). The cytoprotective effects of these compounds were subsequently evaluated using hydrogen peroxide-treated PC12 cells. The cytoprotective effects of the imine analogs were greater than the effects of oxyresveratrol and the other analogs at concentrations of 200 μM. The Compound 3, which is the most effective imine analog of oxyresveratrol, exhibited these cytoprotective effects against hydrogen peroxide-induced oxidative stress through the regulation of heme oxygenase-1 (HO-1) expression and the translocation of nuclear factor E2-related factor 2 (Nrf2). Our results suggest that imine analogs of oxyresveratrol may be useful agents in reducing neuronal oxidative damage.