报告题目 (Title)：Characterisation and Development of Fatty Acid-activated Mitochondrial Uncouplers/脂肪酸激活的线粒体解偶联剂的表征与开发

报告人 (Speaker)： Edward York

报告时间 (Time)：2024年1月9日 (周二) 10:30-11:30

报告地点 (Place)：校本部 HA101

邀请人(Inviter): 雷川虎 教授

主办部门：理学院化学系

报告摘要：

The experimental anticancer agent N,N’-bis(3,5-dichlorophenyl)urea (SR4) induces apoptotic cell death in several cancer cell lines by uncoupling mitochondrial oxidative phosphorylation using a protein-free mechanism. However, the precise mechanism of SR4-mediated uncoupling has not be fully characterised because SR4 lacks an acidic functional group typically required for protonophoric mitochondrial uncoupling. In this work we demonstrate that SR4-mediated proton transport is enhanced by the presence of fatty acids indicating that SR4 uncouples mitochondria through a fatty acid-activated mechanism first identified in 2016 by Wu and Gale. Based on this insight a library of bisaryl urea’s was synthesised for structure-activity relationship (SAR) studies and subsequent cell testing. Lipophilic electron-withdrawing groups enhanced bisaryl urea proton transport activity, and these analogues were shown to depolarise mitochondria and reduce cell viability in human MDA-MB-231 breast cancer cells.

报告人简介：

Dr. Edward York, Doctor of Philosophy – Medicinal Chemistry，University of Technology Sydney