摘要
苯并咪唑及其衍生物因其优异的药用和药理特性而受到广泛关注。研究表明,苯并咪唑具有很好的抗癌活性。然而到目前为止,苯并咪唑与线粒体相互作用的机制还没有很好地阐明。以大鼠离体线粒体为研究对象,系统研究了2-苯基苯并咪唑对离体线粒体功能和结构的影响。实验研究表明,2-苯基苯并咪唑对线粒体肿胀、线粒体内膜对H+和K+的渗透性、线粒体膜电势、膜流动性、线粒体的呼吸产生强烈的影响。线粒体肿胀、跨膜电位下降和膜流动性下降是2-苯基苯并咪唑诱导线粒体MPTP打开的重要因素。这些发现有助于更多的理解2-苯基苯并咪唑在亚细胞水平上的活性,对线粒体靶向药物的研究具有重要意义,将有助于提高线粒体靶向抗癌药物的活性和选择性。
Benzomidazole and its derivatives have attracted the much attention for their remarkable medicinal and pharmacological properties.Multiple studies have shown that benzimidazole has very prominent anti-cancer activity.Until now,however,the mechanism of how benzimidazole interacts with mitochondria has not been well elucidated.Taking rat isolated mitochondria as the research object,the effect of 2-phenylbenzimidazole on the biological function and activity of isolated mitochondria was systematically studied.Through experimental studies,we found that 2-phenylbenzimidazole has strong effects on mitochondrial swelling,mitochondrial membrane permeability to H+and K+,mitochondrial membrane potential,membrane fluidity.Mitochondrial swelling,decreased transmembrane potential and decreased membrane fluidity were important factors for 2-phenylbenzimidazole-induced mitochondrial MPTP opening.These findings help to understand more about the activity of 2-phenylbenzimidazole at the subcellular level,which has great significance for the research of mitochondrial targeting drugs,and will help to improve the activity and selectivity of mitochondrial-targeted anticancer drugs.
作者
焦元红
张晓卉
徐娟
潘凌立
JIAO Yuan-hong;ZHANG Xiao-hui;XU Juan;PAN Ling-li(Hubei Polytechnic University College of Chemistry and Chemical Engineering,Huangshi 435003,China;Hubei Polytechnic University Hubei Key Laboratory of Mine Environmental Pollution Control&Remediation,Huangshi 435003,China;Medical Record Statistics Department,Huangshi Center Hospital,Edong Healthcare Group,Huangshi 435002,China)
出处
《化学试剂》
CAS
北大核心
2023年第5期59-65,共7页
Chemical Reagents
基金
矿区环境污染控制与修复湖北省重点实验室开放基金项目(2020104)。
关键词
2-苯基苯并咪唑
线粒体
线粒体膜渗透性转换
膜流动性
膜电势
2-phenylbenzimidazole
mitochondrial
mitochondrial membrance permeability transition
membrane fluidity
membrane potential
