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

作者：Yan, Jun; Hu, Jinhui; Liu, Anqiu; He, Lin; Li, Xingshu^*; Wei, Hui^*

来源：Bioorganic & Medicinal Chemistry, 2017, 25(12): 2946-2955.

DOI：10.1016/j.bmc.2017.02.048

• Alzheimer's disease
• Curcumin derivatives
• AChE inhibition
• A beta(1)-42 self-aggregation

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 lib also inhibited 45.3% A beta(1-42) self-aggregation at 20 mu M and displayed remarkable antioxidant effects. The metal-chelating property of compound lib 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.

• 出版日期2017-6-15
• 单位广东药科大学; 中山大学