Structure–activity study of fluorine or chlorine‐substituted cinnamic acid derivatives with tertiary amine side chain in acetylcholinesterase and butyrylcholinesterase inhibition

• DOI: 10.1002/ddr.21515
• Publication Date: 2019-01-25T07:59:53Z
• Authors: Xiao‐Hui Gao; Jing‐Jing Tang; Hao‐Ran Liu; Lin‐Bo Liu; Ying‐Zi Liu
• Keywords: Butyrylcholinesterase; Side chain; Tertiary amine; Pyrroline; Cholinesterase; Piperidine; Cinnamic acid

Abstract In this study, a series of new fluorine or chlorine‐substituted cinnamic acid derivatives that contain tertiary amine side chain were designed, synthesized, and evaluated in acetylcholinesterase (AChE) butyrylcholinesterase (BChE) inhibition. The results show almost all the containing (compounds 4a–9d ) exhibit moderate potent activity AChE By contrast, their parent compounds 3a–3f absence moitery poor inhibitory against AChE. For pyrroline piperidine chain, bioactivity inhibition is much intense than those N , ‐diethylamino chain. chlorine substituted position produces significant effect on selectivity Most para ‐substituted BChE, while ortho analogs opposite effect. It worth noticing are exceptions to pattern. Among newly synthesized compounds, 6d most (IC 50 = 1.11 ± 0.08 μmol/L) with high for over BChE (selectivity ratio: 46.58). An enzyme kinetic study suggests it mixed‐type