title: 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.
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, compound 6c 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 compound 6c 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.
authors.affiliation: a College of Chemistry and Chemical Engineering, Hu'nan University , Changsha , China and.
authors.forename: Haoran
authors.initials: H
authors.lastname: Liu
authors.affiliation: a College of Chemistry and Chemical Engineering, Hu'nan University , Changsha , China and.
authors.forename: Haoqun
authors.initials: H
authors.lastname: Fan
authors.affiliation: b College of Pharmacy, Hu'nan University of Chinese Medicine , Changsha , China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Gao
authors.affiliation: a College of Chemistry and Chemical Engineering, Hu'nan University , Changsha , China and.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Huang
authors.affiliation: a College of Chemistry and Chemical Engineering, Hu'nan University , Changsha , China and.
authors.forename: Xianjun
authors.initials: X
authors.lastname: Liu
authors.affiliation: a College of Chemistry and Chemical Engineering, Hu'nan University , Changsha , China and.
authors.forename: Linbo
authors.initials: L
authors.lastname: Liu
authors.affiliation: a College of Chemistry and Chemical Engineering, Hu'nan University , Changsha , China and.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhou
authors.affiliation: a College of Chemistry and Chemical Engineering, Hu'nan University , Changsha , China and.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Tang
authors.affiliation: a College of Chemistry and Chemical Engineering, Hu'nan University , Changsha , China and.
authors.forename: Qiuan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: a College of Chemistry and Chemical Engineering, Hu'nan University , Changsha , China and.
authors.forename: Wukun
authors.initials: W
authors.lastname: Liu
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002599:Chalcone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008352:Mannich Bases / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D005419:Flavonoids; D008352:Mannich Bases; C452039:flavokawain B; D002599:Chalcone; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D009584:Nitrogen
keywords: Acetylcholinesterase inhibitors; Alzheimer's disease; chalcones; structure–activity relationship