Design, synthesis and preliminary structure–activity relationship investigation of nitrogen-containing chalcone derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors: a further study based on Flavokawain B Mannich base derivatives. (3rd July 2016)

• Record Type: Journal Article
• Authors: Liu, Haoran; Fan, Haoqun; Gao, Xiaohui; Huang, Xueqing; Liu, Xianjun; Liu, Linbo; Zhou, Chao; Tang, Jingjing; Wang, Qiuan; Liu, Wukun
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 31(2016.)Supplement 4
• Page Start: 580
• Page End: 589
• Publication Date: 2016-07-03
• Subjects: Acetylcholinesterase inhibitors -- Alzheimer's disease -- chalcones -- structure–activity relationship; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.3109/14756366.2015.1050009
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: In order to study the structure–activity relationship of Flavokawain B Mannich-based derivatives as acetylcholinesterase (AChE) inhibitors in our recent investigation, 20 new nitrogen-containing chalcone derivatives (4 a–8d ) were designed, synthesized, and evaluated for AChE inhibitory activity in vitro . The results suggested that amino alkyl side chain of chalcone dramatically influenced the inhibitory activity against AChE. Among them, compound6c revealed the strongest AChE inhibitory activity (IC50 value: 0.85 μmol/L) and the highest selectivity against AChE over BuChE (ratio: 35.79). Enzyme kinetic study showed that the inhibition mechanism of compound6c against AChE was a mixed-type inhibition. The molecular docking assay showed that this compound can both bind with the catalytic site and the peripheral site of AChE.