Structure–activity relationship investigation of tertiary amine derivatives of cinnamic acid as acetylcholinesterase and butyrylcholinesterase inhibitors: compared with that of phenylpropionic acid, sorbic acid and hexanoic acid

Journal of Enzyme Inhibition and Medicinal Chemistry

Linbo Liu¹  Lu Kang¹  Haoran Liu¹  Jingjing Tang¹  Wen Chen²  Xiaohui Gao³ 

[1] College of Chemistry and Chemical Engineering, Hu’nan University, Changsha, China;Department of Pharmacy, Huizhou Health Sciences Polytechnic, Huizhou, Chin;Key Laboratory Breeding Base of Hu’nan Oriented Fundamental and Applied Research of Innovative Pharmaceutics, College of Pharmacy, Changsha Medical University, Changsha, China;

关键词: Cinnamic acid;    tertiary amine;    AChE inhibitors;    benzene ring;    double bond;   

DOI  :  10.1080/14756366.2018.1436053

来源: publisher

【 摘 要 】

In the present investigation, 48 new tertiary amine derivatives of cinnamic acid, phenylpropionic acid, sorbic acid and hexanoic acid (4d–6g, 10d–12g, 16d–18g and 22d–24g) were designed, synthesized and evaluated for the effect on AChE and BChE in vitro. The results revealed that the alteration of aminoalkyl types and substituted positions markedly influences the effects in inhibiting AChE. Almost of all cinnamic acid derivatives had the most potent inhibitory activity than that of other acid derivatives with the same aminoalkyl side chain. Unsaturated bond and benzene ring in cinnamic acid scaffold seems important for the inhibitory activity against AChE. Among them, compound 6g revealed the most potent AChE inhibitory activity (IC50 value: 3.64 µmol/L) and highest selectivity over BChE (ratio: 28.6). Enzyme kinetic study showed that it present a mixed-type inhibition against AChE. The molecular docking study suggested that it can bind with the catalytic site and peripheral site of AChE.

【 授权许可】

CC BY