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

Abstract

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

CLC Number:

R965

CHU Shi-feng, ZHANG Jun-tian. A New Type of Anti-dementia Drug: The Chemistry, Biological Activities and Mechanism of Action of (-) Clausenamide[J]. Acta Neuropharmacologica, 2014, 4(6): 33-43.

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