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

Molecules (Oct 2016)

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

Affiliations

Yingbo Fu: Laboratory of Metabolic Disease Research and Drug Development, China Medical University, Shenyang 110001, China
Yu Mu: Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China
Hui Lei: Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China
Pu Wang: Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China
Xin Li: Laboratory of Metabolic Disease Research and Drug Development, China Medical University, Shenyang 110001, China
Qiao Leng: Laboratory of Metabolic Disease Research and Drug Development, China Medical University, Shenyang 110001, China
Li Han: Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China
Xiaodan Qu: Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China
Zhanyou Wang: Laboratory of Metabolic Disease Research and Drug Development, China Medical University, Shenyang 110001, China
Xueshi Huang: Laboratory of Metabolic Disease Research and Drug Development, China Medical University, Shenyang 110001, China

DOI: https://doi.org/10.3390/molecules21101338
Journal volume & issue: Vol. 21, no. 10
p. 1338

Abstract

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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.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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