School of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, 2007, Australia.
School of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, 2007, Australia.
Chem Biol Interact. 2024 Jun 1;396:111042. doi: 10.1016/j.cbi.2024.111042. Epub 2024 May 10.
Ionic liquids (ILs) are a class of low melting point salts with physicochemical properties suitable for a range of industrial applications such as chemical processing and battery design. Major challenges to the wide-scale adoption of ILs in industry include their eco- and cytotoxic effects, however, this opens up the possibility of the use of ILs use as novel anticancer agents. Understanding the structural features that promote IL cytotoxicity is therefore important. Key structural features that can impact IL cytotoxicity include size and lipophilicity of the cationic head group. In this study, the cytotoxic effects of acridinium-based ILs containing relatively large tri- and tetracyclic cations were evaluated. It was found that 9-phenylacridinium-based ILs are potent cytotoxic agents that reduce the viability of human MDA-MB-231 breast cancer cells with IC concentrations in the nanomolar range. In mechanistic studies, it was found that unlike the pyridinium-based analogue, [CPy][I], acridinium-based ILs did not inhibit oxidative phosphorylation or induce reactive oxygen species formation, and may instead target other mitochondrial processes or components such as mitochondrial DNA.
离子液体（ILs）是一类低熔点盐，具有适合一系列工业应用的物理化学性质，例如化学加工和电池设计。在工业中广泛采用 ILs 的主要挑战包括它们的生态和细胞毒性效应，但这也为将 ILs 用作新型抗癌剂开辟了可能性。因此，了解促进 IL 细胞毒性的结构特征非常重要。可能影响 IL 细胞毒性的关键结构特征包括阳离子头基的大小和亲脂性。在这项研究中，评估了含有相对较大的三环和四环阳离子的基于吖啶的 IL 的细胞毒性作用。结果发现，基于 9-苯基吖啶的 IL 是有效的细胞毒性剂，可将人 MDA-MB-231 乳腺癌细胞的活力降低至纳摩尔范围内的 IC 浓度。在机制研究中，与吡啶鎓类似物[CPy][I]不同，基于吖啶的 IL 不会抑制氧化磷酸化或诱导活性氧形成，而可能针对其他线粒体过程或成分，例如线粒体 DNA。
