Department of Natural Products Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
Eur J Med Chem. 2013 Apr;62:187-98. doi: 10.1016/j.ejmech.2012.12.037. Epub 2013 Jan 5.
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.
设计、合成了 3 种白藜芦醇类似物，并在体外对 SH-SY5Y 细胞中甲氧滴滴涕诱导的细胞凋亡进行了评价。结果表明，部分化合物，特别是含有茚并核心的化合物，表现出良好的活性。类似物 3'a 在低浓度（10 μM）时表现出很强的神经保护作用。进一步的研究表明，化合物 3'a 可以减轻甲氧基滴滴涕诱导的核形态变化，显著降低 SH-SY5Y 细胞中甲氧滴滴涕诱导的 ROS（活性氧）生成，并呈剂量依赖性方式提高 SOD（超氧化物歧化酶）和 GPx（谷胱甘肽过氧化物酶）的表达。此外，类似物 3'a 可以浓度依赖性地降低 Bax 蛋白水平，增加 Bcl-2 蛋白表达，从而增加细胞存活的机会。
