Design, synthesis and pharmacological evaluation of chalcone derivatives as acetylcholinesterase inhibitors

作者：Liu, Hao-ran^*; Liu, Xian-jun; Fan, Hao-qun; Tang, Jing-jing; Gao, Xiao-hui; Liu, Wu-kun

来源：Bioorganic & Medicinal Chemistry, 2014, 22(21): 6124-6133.

DOI：10.1016/j.bmc.2014.08.033

• Chalcone derivatives
• AChE inhibitors
• LogP
• Molecular docking

A novel series of chalcone derivatives (4a-8d) were designed, synthesized, and evaluated for the inhibition activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The logP values of the compounds were shown to range from 1.49 to 2.19, which suggested that they were possible to pass blood brain barriers in vivo. The most promising compound 4a (IC50: 4.68 mu mol/L) was 2-fold more potent than Rivastigmine against AChE (IC50: 10.54 mu mol/L) and showed a high selectivity for AChE over BuChE (ratio: 4.35). Enzyme kinetic study suggested that the inhibition mechanism of compound 4a was a mixed-type inhibition. Meanwhile, the result of molecular docking showed its potent inhibition of AChE and high selectivity for AChE over BuChE.

• 出版日期2014-11-1
• 单位湖南中医药大学; 湖南大学