Synthesis and evaluation of oxime derivatives as modulators for amyloid beta-induced mitochondrial dysfunction

Young Seub Kim, Sun Hwa Jung, Beoung Geon Park, Min Kyung Ko, Hyun Seo Jang, Kihang Choi, Ja Hyun Baik, Jiyoun Lee, Jae Kyun Lee, Ae Nim Pae, Yong Seo Cho, Sun Joon Min

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Starting from quinuclidinyl oxime 1 identified by preliminary screening, a series of azacycles-containing oxime derivatives was synthesized. Their mPTP blocking activities were evaluated by a JC-1 assay, measuring the change of mitochondrial membrane potential. The inhibitory activity of nine compounds against amyloid beta-induced mPTP opening was comparable or even superior to that of piracetam. Among them, 12d effectively maintained mitochondrial function and cell viabilities on the ATP assay, the MTT assay, and the ROS assay. In addition, it exhibited favorable in vitro stability and pharmacokinetic characteristics, which hold a promise for further development of AD therapeutics.

Original languageEnglish
Pages (from-to)71-83
Number of pages13
JournalEuropean Journal of Medicinal Chemistry
Volume62
DOIs
Publication statusPublished - 2013 Apr 1

Keywords

  • Alzheimer's disease
  • Amyloid beta
  • Mitochondrial permeability transition pore (mPTP)
  • Oxime derivatives
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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