Design, synthesis, and evaluation of multitarget-directed ligands against Alzheimer’s disease based on the fusion of donepezil and curcumin

Publication date: Available online 18 April 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Jun Yan, Jinhui Hu, Anqiu Liu, Lin He, Xingshu Li, Hui Wei
By fusing donepezil and curcumin, a novel series of compounds were obtained as multitarget-directed ligands against Alzheimer's disease. Among them, compound 11b displayed potent acetylcholinesterase (AChE) inhibition (IC50 = 187 nM) and the highest BuChE/AChE selectivity (66.3). Compound 11b also inhibited 45.3% Aβ1−42 self-aggregation at 20 μM and displayed remarkable antioxidant effects. The metal-chelating property of compound 11b was elucidated by determining the 1:1 stoichiometry for the 11b−Cu(II) complex. The excellent blood−brain barrier permeability of 11b also indicated the potential for the compound to penetrate the central nervous system.

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