Development of huperzine A and B for treatment of Alzheimer's disease
Donglu Bai
Shanghai Institute of Materia Medica, Chinese Academy of Sciences,555 Zuchongzhi Road, Shanghai, 201203, China
Abstract: Recent studies have proved that huperzine A (HupA) possesses different pharmacological actions other than the inhibition of hydrolysis of ACh. These noncholinergic roles, for instance, the antagonist effect on NMDA receptor, the protection of neuronal cells against β-amyloid, free radicals, and hypoxia-ischemia-induced injury, could be important too in Alzheimer's disease (AD) treatment. The therapeutic effects of HupA are probably based on a multitarget mechanism. By targeting dual active sites of AChE, a series of bis- and bifunctional HupB compounds with various lengths of tether were designed, synthesized, and tested for the inhibition and selectivity of AChE. The most potent bis-HupB compound exhibited increase by three orders of magnitude in AChE inhibition and two orders of magnitude in selectivity for AChE than its parent HupB.
Keywords: acetylcholinesterase inhibitors; butyrocholinesterase inhibitors; huperzine A; huperzine B; Alzheimer's disease; dimers.
*Pure Appl. Chem. 79, 467-823 (2007) pp. 467-823. An issue of reviews and research papers based on lectures presented at the 25th International Symposium on Chemistry of Natural Products (ISCNP-25) and 5th International Conference on Biodiversity (ICOB-5), held jointly in Kyoto, Japan, 23-28 July 2006, on the theme of natural products.