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新型神经保护剂的合成及对百草枯诱导的人神经母细胞瘤 SH-SY5Y 细胞凋亡的作用研究。

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

机构信息

Department of Natural Products Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.

出版信息

Eur J Med Chem. 2013 Apr;62:187-98. doi: 10.1016/j.ejmech.2012.12.037. Epub 2013 Jan 5.

Abstract

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.

摘要

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。

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