Natural products as sources of new lead compounds for the treatment of Alzheimer's disease.
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.
Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yatsen University, Guangzhou 510006, China.
Ling
L
Huang
Tao
T
Su
Xingshu
X
Li
D000110:Acetylcholinesterase / Q000378:metabolism; D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification* / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000627:therapeutic use; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use; D055808:Drug Discovery; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use; D006801:Humans; D018697:Nootropic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000627:therapeutic use; D013267:Stilbenes / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D000470:Alkaloids; D001688:Biological Products; D002800:Cholinesterase Inhibitors; D003374:Coumarins; D005419:Flavonoids; D018697:Nootropic Agents; D013267:Stilbenes; D000110:Acetylcholinesterase