Department of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, P J Safárik University, Kosice, Slovak Republic.
FEBS Lett. 2010 Feb 5;584(3):567-70. doi: 10.1016/j.febslet.2009.11.098. Epub 2009 Dec 9.
We investigated the effect of hydroxyl substituted chalcone (1a) and some chalcone analogues (1b-d) on isolated rat liver mitochondria to gain new insights into the cytotoxic mechanism of these compounds. We observed an inhibitory effect on phosphorylation and the partial uncoupling of compounds 1a and 1d. Increased radical generation and possible covalent interaction of the compounds with cellular thiols resulted in glutathione (GSH) depletion and modulation of the investigated mitochondrial activities. Disruption of interconnected mechanisms as electron transport chain and energetic metabolism, ROS production and insufficiency of antioxidant defensive system could lead to induction of cell death.
我们研究了羟基取代查耳酮（1a）和一些查耳酮类似物（1b-d）对分离的大鼠肝线粒体的影响，以期深入了解这些化合物的细胞毒性机制。我们观察到化合物 1a 和 1d 对磷酸化有抑制作用，并部分解偶联。自由基的生成增加，以及化合物与细胞巯基的可能共价相互作用，导致谷胱甘肽（GSH）耗竭，并调节所研究的线粒体活性。电子传递链和能量代谢、ROS 产生以及抗氧化防御系统不足等相互关联的机制的破坏，可能导致细胞死亡的诱导。
