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Updated: May 14, 2026

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
Synthesis and evaluation of oxime derivatives as modulators for amyloid beta-induced mitochondrial dysfunction
Young Seub Kim1, Sun Hwa Jung, Beoung-Geon Park
1Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, South Korea.
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.
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