Design, synthesis and evaluation of flavonoid derivatives as potential multifunctional acetylcholinesterase inhibitors against Alzheimer's disease

Renshi Li, Xiao Bing Wang, Xiao Jun Hu, Ling Yi Kong

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

A new series of flavonoid derivatives were designed, synthesized and evaluated as potential multifunctional AChE inhibitors against Alzheimer's disease. Most of them exhibited potent AChE inhibitory activity, high selectivity for AChE over BuChE, and moderate to good inhibitory potency toward Aβ aggregation. Specifically, compound 12c was the strongest AChE inhibitor, being 20-fold more potent than galanthamine and twofold more potent than tacrine, and it also had ability to inhibit Aβ aggregation (close to the reference compound) and to function as a metal chelator. Molecular modeling and enzyme kinetic study revealed that it targeted both the catalytic active site and the peripheral anionic site of AChE. Consequently, this class of compounds deserved to be thoroughly and systematically studied for the treatment of Alzheimer's disease.

Original languageEnglish
Pages (from-to)2636-2641
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number9
DOIs
Publication statusPublished - May 1 2013

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Cholinesterase Inhibitors
Flavonoids
Catalytic Domain
Alzheimer Disease
Agglomeration
Galantamine
Derivatives
Tacrine
Enzyme kinetics
Aptitude
Molecular modeling
Chelating Agents
Metals
Enzymes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Design, synthesis and evaluation of flavonoid derivatives as potential multifunctional acetylcholinesterase inhibitors against Alzheimer's disease. / Li, Renshi; Wang, Xiao Bing; Hu, Xiao Jun; Kong, Ling Yi.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 23, No. 9, 01.05.2013, p. 2636-2641.

Research output: Contribution to journalArticle

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