Synthesis and biological evaluation of novel neuroprotective agents for paraquat-induced apoptosis in human neuronal SH-SY5Y cells

Three types of resveratrol analogues were designed, synthesized and evaluated in vitro against paraquat-induced apoptosis in SH-SY5Y cells. The results showed that some compounds, especially those containing an indene core, exhibit good activities. Analogue 3′a showed a potent neuroprotective effect at a low concentration (10 μM). Further investigation showed that compound 3′a could attenuate paraquat-induced nuclear morphological changes, significantly decrease paraquat-induced ROS (reactive oxygen species) generation in SH-SY5Y cells and elevate the expression of SOD (Superoxide Dismutase) and GPx (glutathione peroxidase) in a dose-dependent manner. Furthermore, analogue 3′a could decrease Bax protein levels in a concentration-dependent manner and increase Bcl-2 protein expression, which was accompanied by increasing chances of cell survival.

Three types of novel neuroprotective agents were designed, synthesized and evaluated in vitro in human neuronal SH-SY5Y cells.Figure optionsDownload as PowerPoint slideHighlights
► Three types of novel neuroprotective agents were designed and synthesized.
► Analogues exhibited activities in vitro against paraquat-induced apoptosis.
► The most potent compound 3′a was chosen for further investigation.