Design, Synthesis and Evaluation of Novel Tacrine-Ferulic Acid Hybrids as Multifunctional Drug Candidates against Alzheimer's Disease

Yingbo Fu; Yu Mu; Hui Lei; Pu Wang; Xin Li; Qiao Leng; Li Han; Xiaodan Qu; Zhanyou Wang; Xueshi Huang

doi:10.3390/molecules21101338

Design, Synthesis and Evaluation of Novel Tacrine-Ferulic Acid Hybrids as Multifunctional Drug Candidates against Alzheimer's Disease

Molecules. 2016 Oct 11;21(10):1338. doi: 10.3390/molecules21101338.

Authors

Yingbo Fu¹, Yu Mu², Hui Lei³, Pu Wang⁴, Xin Li⁵, Qiao Leng⁶, Li Han⁷, Xiaodan Qu⁸, Zhanyou Wang⁹, Xueshi Huang^{10

11}

Affiliations

¹ Laboratory of Metabolic Disease Research and Drug Development, China Medical University, Shenyang 110001, China. fuyb@mail.neu.edu.cn.
² Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. muyu@mail.neu.edu.cn.
³ Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. leihui-2008@163.com.
⁴ Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. wangpu@mail.neu.edu.cn.
⁵ Laboratory of Metabolic Disease Research and Drug Development, China Medical University, Shenyang 110001, China. fly1982_2008@sina.com.
⁶ Laboratory of Metabolic Disease Research and Drug Development, China Medical University, Shenyang 110001, China. leng_qiao@yahoo.com.
⁷ Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. hanli@mail.neu.edu.cn.
⁸ Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. x.qu@hotmail.com.
⁹ Laboratory of Metabolic Disease Research and Drug Development, China Medical University, Shenyang 110001, China. wangzy@mail.neu.edu.cn.
¹⁰ Laboratory of Metabolic Disease Research and Drug Development, China Medical University, Shenyang 110001, China. huangxs@mail.neu.edu.cn.
¹¹ Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. huangxs@mail.neu.edu.cn.

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, 8c and 8d displayed the higher selectivity in inhibiting AChE over BuChE. Moreover, 8d also showed dramatic inhibition of self-Aβ aggregation, activity of chelating Cu²⁺ and activity against Aβ-induced neurotoxicity in Neuro-2A cells.

Keywords: cholinesterase; ferulic acid; metal chelator; neuroprotection; tacrine; β-amyloid aggregation.

MeSH terms

Acetylcholinesterase / metabolism
Alzheimer Disease / drug therapy
Alzheimer Disease / metabolism*
Amyloid beta-Peptides / metabolism
Butyrylcholinesterase / metabolism
Cell Line
Cell Survival / drug effects
Chelating Agents / chemical synthesis*
Chelating Agents / chemistry
Chelating Agents / pharmacology
Cholinesterase Inhibitors / chemical synthesis*
Cholinesterase Inhibitors / chemistry
Cholinesterase Inhibitors / pharmacology*
Coumaric Acids / chemistry*
Coumaric Acids / pharmacology
Drug Design
Humans
Molecular Docking Simulation
Molecular Structure
Structure-Activity Relationship
Tacrine / chemistry*
Tacrine / pharmacology

Substances

Amyloid beta-Peptides
Chelating Agents
Cholinesterase Inhibitors
Coumaric Acids
Tacrine
ferulic acid
Acetylcholinesterase
Butyrylcholinesterase