title: Novel Potent and Selective Acetylcholinesterase Inhibitors as Potential Drugs for the Treatment of Alzheimer's Disease: Synthesis, Pharmacological Evaluation, and Molecular Modeling of Amino-Alkyl-Substituted Fluoro-Chalcones Derivatives.
abstract: A new series of-fluoro chalcones-substituted amino-alkyl derivatives (3a˜3l) were designed, synthesized, characterized and evaluated for the inhibitory activity against acetylcholinesterase and butyrylcholinesterase. The results showed that the alteration of fluorine atom position and amino-alkyl groups markedly influenced the activity and the selectivity of chalcone derivates in inhibiting acetylcholinesterase and butyrylcholinesterase. Among them, compound 3l possesses the most potent inhibitory against acetylcholinesterase (IC50  = 0.21 ± 0.03 μmol/L), and the highest selectivity for acetylcholinesterase over butyrylcholinesterase (IC50 (BuChE)/IC50 (AChE) = 65.0). Molecular modeling and enzyme kinetic study on compound 3l supported its dual acetylcholinesterase inhibitory profile, simultaneously binding at the catalytic active and peripheral anionic site of the enzyme.
authors.affiliation: College of Chemistry and Chemical Engineering, Hu'nan University, Changsha, 410082, China.
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: Chao
authors.initials: C
authors.lastname: Zhou
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 Chemistry and Chemical Engineering, Hu'nan University, Changsha, 410082, China.
authors.forename: Lin-Bo
authors.initials: LB
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Hu'nan University of Chinese Medicine, 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: Qiu-An
authors.initials: QA
authors.lastname: Wang
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*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology; D000818:Animals; D047188:Chalcones / Q000737:chemistry* / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry* / Q000627:therapeutic use; D062105:Molecular Docking Simulation
chemical_list: D047188:Chalcones; D002800:Cholinesterase Inhibitors; D006845:Hydrocarbons, Fluorinated; D000110:Acetylcholinesterase
keywords: AChE inhibitors; chalcone; fluorine; molecular modeling; selectivity