East Meets West in Fighting Against Alzheimer’s Disease with Novel Dimers
Alzheimer’s disease (AD), a progressive brain disorder that severely destroys memory, has emerged as the third leading cause of death among the elderly. Three series of Chinese medicine-derived novel anti-AD homo- and hetero-dimers particularly those derived from huperzine A are developed.
The cost to synthesize these new dimers is much lower than that to isolate HupA from the natural plant. The idea of dimerization is a novel concept to modify the existing drugs. The dimerisation of available drugs is one of most effective and economical strategies for developing multifunctional drugs. According to the above properties, tacrine and hupyridone are chosen as moieties for synthesizing novel dimers with low side effects. Comprehensive comparisons of these dimers and the existing agents with regard to their AChE inhibitions, neuroprotection and memory-enhancing effects were conducted. The results suggest that these novel multi-functional analogs can be highly promising drug candidates for AD and other neurodegenerative diseases.