title: Design, Synthesis and Evaluation of Novel Tacrine-Ferulic Acid Hybrids as Multifunctional Drug Candidates against Alzheimer's Disease.
abstract: Five novel tacrine-ferulic acid hybrid compounds (8a-e) were synthesized and their structures were identified on the basis of a detailed spectroscopic analysis. The activities of inhibiting acetyl cholinesterase (AChE) and butyryl cholinesterase (BuChE), reducing self-induced β-amyloid (Aβ) aggregation and chelating Cu2+were evaluated in vitro. Among them,8cand8ddisplayed the higher selectivity in inhibiting AChE over BuChE. Moreover,8dalso showed dramatic inhibition of self-Aβ aggregation, activity of chelating Cu2+and activity against Aβ-induced neurotoxicity in Neuro-2A cells.
authors.affiliation: Laboratory of Metabolic Disease Research and Drug Development, China Medical University, Shenyang 110001, China. fuyb@mail.neu.edu.cn.
authors.forename: Yingbo
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. muyu@mail.neu.edu.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Mu
authors.affiliation: Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. leihui-2008@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Lei
authors.affiliation: Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. wangpu@mail.neu.edu.cn.
authors.forename: Pu
authors.initials: P
authors.lastname: Wang
authors.affiliation: Laboratory of Metabolic Disease Research and Drug Development, China Medical University, Shenyang 110001, China. fly1982_2008@sina.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Laboratory of Metabolic Disease Research and Drug Development, China Medical University, Shenyang 110001, China. leng_qiao@yahoo.com.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Leng
authors.affiliation: Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. hanli@mail.neu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Han
authors.affiliation: Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. x.qu@hotmail.com.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Qu
authors.affiliation: Laboratory of Metabolic Disease Research and Drug Development, China Medical University, Shenyang 110001, China. wangzy@mail.neu.edu.cn.
authors.forename: Zhanyou
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Laboratory of Metabolic Disease Research and Drug Development, China Medical University, Shenyang 110001, China. huangxs@mail.neu.edu.cn.|Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. huangxs@mail.neu.edu.cn.
authors.forename: Xueshi
authors.initials: X
authors.lastname: Huang
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D002091:Butyrylcholinesterase / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003373:Coumaric Acids / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013619:Tacrine / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D002614:Chelating Agents; D002800:Cholinesterase Inhibitors; D003373:Coumaric Acids; D013619:Tacrine; C004999:ferulic acid; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: cholinesterase; ferulic acid; metal chelator; neuroprotection; tacrine; β-amyloid aggregation