Natural Products as Sources of New Lead Compounds for the Treatment of Alzheimer’s Disease

Ling      Huang; Tao      Su; Xingshu      Li

doi:10.2174/15680266113139990142

Abstract

Alzheimer’s disease (AD) is the most prevalent form of dementia and affects approximately 24 million people worldwide. One possible approach for the treatment of this disease is the restoration of the level of acetylcholine (ACh) through the inhibition of acetylcholinesterase (AChE) with reversible inhibitors. Naturally occurring alkaloids are an important source of AChE inhibitors. Galantamine and huperzine A have been used for the clinical treatment of AD patients. In this review, we summarise the natural products and their derivatives that were reported to act as AChE inhibitors for the treatment of AD in 2010-2013. Several characteristics were summarised from the literature results: 1) Amongst all of the natural products with AChE inhibitory activity, alkaloids appear to be the most promising compound class. 2) Coumarins, flavonoids, stilbenes, and other natural products are also important AChE inhibitors from natural products. Among these inhibitors, 146 (IC₅₀ = 0.573 µM) was identified as the most potent AChE inhibitor. 3) A coumarin derivative (117, IC₅₀ = 0.11 nM) exhibited more than 100-fold superior activity compared with the reference drug donepezil hydrochloride (IC₅₀ = 14 nM). In conclusion, natural products and their derivatives are promising leads for the development of new drugs for the future treatment of AD.

Keywords: Acetylcholinesterase inhibitors, Alzheimer’s disease, Alkaloids, Coumarins, Docking study, Flavonoids, Natural products, Structure-activity relationship.