title: Design, synthesis and pharmacological evaluation of chalcone derivatives as acetylcholinesterase inhibitors.
abstract: 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 μmol/L) was 2-fold more potent than Rivastigmine against AChE (IC50: 10.54 μmol/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.
authors.affiliation: College of Chemistry and Chemical Engineering, Hu'nan University, Changsha 410082, China. Electronic address: pharmaliu@126.com.
authors.forename: Hao-ran
authors.initials: HR
authors.lastname: Liu
authors.affiliation: College of Chemistry and Chemical Engineering, Hu'nan University, Changsha 410082, China.
authors.forename: Xian-jun
authors.initials: XJ
authors.lastname: Liu
authors.affiliation: College of Chemistry and Chemical Engineering, Hu'nan University, Changsha 410082, China.
authors.forename: Hao-qun
authors.initials: HQ
authors.lastname: Fan
authors.affiliation: College of Chemistry and Chemical Engineering, Hu'nan University, Changsha 410082, China.
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Tang
authors.affiliation: College of Pharmacy, Hu'nan University of Traditional Chinese Medicine (TCM), Changsha 410208, China.
authors.forename: Xiao-hui
authors.initials: XH
authors.lastname: Gao
authors.affiliation: College of Chemistry and Chemical Engineering, Hu'nan University, Changsha 410082, China.
authors.forename: Wu-Kun
authors.initials: WK
authors.lastname: Liu
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000378:metabolism; D002599:Chalcone / Q000737:chemistry* / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship; D014101:Torpedo
chemical_list: D002800:Cholinesterase Inhibitors; D002599:Chalcone; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: AChE inhibitors; Chalcone derivatives; LogP; Molecular docking