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

Ren Shi Li, Xiao Bing Wang, Xiao Jun Hu, Ling Yi Kong

研究成果: Contribution to journalArticle査読

75 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)2636-2641
ページ数6
ジャーナルBioorganic and Medicinal Chemistry Letters
23
9
DOI
出版ステータス出版済み - 5 1 2013

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子医療
  • 分子生物学
  • 薬科学
  • 創薬
  • 臨床生化学
  • 有機化学

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