Acta Neuropharmacologica››2014,Vol. 4››Issue (6): 33-43.

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A New Type of Anti-dementia Drug: The Chemistry, Biological Activities and Mechanism of Action of (-) Clausenamide

CHU Shi-feng, ZHANG Jun-tian

  1. Institute of material medica, Chinese academy of medical sciences, China
  • Online:2014-12-26Published:2015-01-20
  • Contact:张均田,男,博士生导师;研究方向:神经药理学;E-mail:zhangjt@imm.ac.cn
  • About author:楚世峰,男;研究方向:神经药理学
  • Supported by:

    本项目得到科技部973计划的资助,已取得中国、美国和欧盟专利证书,获教育部自然科学奖一等奖,中华医学奖二等奖,北京市科技进步奖二等奖各一项,在SCI杂志上发表的论文五十余篇。

Abstract:Seven novel amides were isolated from clausena lansium (Lour) skeels, one of which is clausenamide. Clausenamide contains 4 chiral centers, which correspond to 16 enantiomers. After the identification of the configuration of 16 enantiomers, all were successfully synthesized, and the asymmetric synthesis of (+) and (-) clausenamide were completed. During this process, the production scale has been substantially increased that should be adequate to meet the clinical use. Pharmacological studies have shown that (-) clausenamide is the effective enantiomer, while (+) clausenamide is ineffective and more toxic than (-)clausenamide using different animal models. (-)clausenamide can increase cognitive function and inhibit Aβ pathology. The anti-dementia mechanism is characterized as increasing synaptic function and structural plasticity. . Together, (-)clausenamide may be a promising pharmacotherapy for the treatment of AD and other neurodegenerative disorders.

Key words:(-) clausenamide,enantiomers,cognition,Alzheimer&,rsquo,s disease (AD),synaptic plasticity

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