设计、合成及生物评价 LX2343 衍生物作为治疗阿尔茨海默病的神经保护剂。
Design, synthesis and biological evaluation of LX2343 derivatives as neuroprotective agents for the treatment of Alzheimer's disease.
机构信息
Jiangsu Key Laboratory for Functional Substance of Chinese Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Stake Key Laboratory Cultivation Base for TCM Quality and Efficacy, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
Jiangsu Key Laboratory for Functional Substance of Chinese Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Stake Key Laboratory Cultivation Base for TCM Quality and Efficacy, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China.
出版信息
Eur J Med Chem. 2018 Feb 10;145:622-633. doi: 10.1016/j.ejmech.2017.12.080. Epub 2018 Jan 2.
A series of LX2343 derivatives were designed, synthesized and evaluated as neuroprotective agents for Alzheimer's disease (AD) in vitro. Most of the compounds displayed potent neuroprotective activities. Especially for compound A6, exhibited a remarkable EC value of 0.22 μM. Further investigation demonstrated that compound A6 can significantly reduce Aβ production and increase Aβ clearance, and alleviate Tau hyperphosphorylation. Most importantly, compound A6 could ameliorate learning and memory impairments in APP/PS1 transgenic mice. The present study evidently showed that compound A6 is a potent neuroprotective agent and might serve as a promising lead candidate for the treatment of Alzheimer's disease.
一系列 LX2343 衍生物被设计、合成并评估为阿尔茨海默病（AD）的神经保护剂。大多数化合物表现出很强的神经保护活性。特别是化合物 A6，其 EC 值达到了 0.22 μM。进一步的研究表明，A6 可以显著减少 Aβ的产生和增加 Aβ的清除，并减轻 Tau 的过度磷酸化。最重要的是，A6 可以改善 APP/PS1 转基因小鼠的学习和记忆障碍。本研究表明 A6 是一种有效的神经保护剂，可能是治疗阿尔茨海默病的有前途的先导化合物。
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