Authors: XianLe Bu Praveen P N Rao YanJiang Wang
Publish Date: 2015/06/23
Volume: 53, Issue: 6, Pages: 3565-3575
Abstract
Several plantderived natural compounds are known to exhibit antiamyloid aggregation activity which makes them attractive as potential therapies to treat Alzheimer’s disease The mechanisms of their antiamyloid activity are not well known In this regard many natural compounds are known to exhibit direct binding to various amyloid species including oligomers and fibrils which in turn can lead to conformational change in the betasheet assembly to form nontoxic aggregates This review discusses the mechanism of antiamyloid activity of 16 natural compounds and gives structural details on their direct binding interactions with amyloid aggregates Our computational investigations show that the physicochemical properties of natural products do fit Lipinski’s criteria and that catechol and catecholtype moieties present in natural compounds act as lysine sitespecific inhibitors of amyloid aggregation Based on these observations we propose a structural template to design novel small molecules containing sitespecific ring scaffolds planar aromatic and nonaromatic linkers with suitably substituted hydrogen bond acceptors and donors These studies will have significant implications in the design and development of novel amyloid aggregation inhibitors with superior metabolic stability and bloodbrain barrier penetration as potential agents to treat Alzheimer’s diseaseThis work is supported by the National Natural Science Foundation of China grant numbers 81270423 and 81471296 for YJW and NSERCDiscovery RGPIN 038302014 MitacsCanada and Early Researcher Award from the Ministry of Research and Innovation Government of Ontario Canada for PPNR
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