Department of Chemistry, King's College London, London, SE1 1DB, UK.
College of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing, 314001, China.
Chemistry. 2018 Oct 12;24(57):15205-15210. doi: 10.1002/chem.201803521. Epub 2018 Sep 10.
The cancer stem cell (CSC) toxicity and mechanism of action of a series of iridium(III) complexes bearing polypridyl and charged 1-methyl-2-(2-pyridyl)pyridinium ligands, 1-4 is reported. The most effective complex (containing 1,10-phenanthroline), 3, kills CSCs and bulk cancer cells with equal potency (in the micromolar range), indicating that it could potentially remove heterogenous tumour populations with a single dose. Encouragingly, 3 also inhibits mammopshere formation to a similar extent as salinomycin, a well-established anti-CSC agent. This complex induces CSC apoptosis by mitochondrial membrane depolarization, inhibition of mitochondrial metabolism, and intracellular reactive oxygen species (ROS) generation. To the best of our knowledge, this is the first study to investigate the anti-CSC properties of iridium complexes.
报道了一系列带有多吡啶和带电荷的 1-甲基-2-(2-吡啶基)吡啶鎓配体的铱(III)配合物的抗癌干细胞 (CSC) 毒性和作用机制，这些配合物分别为 1-4。最有效的配合物（含有 1,10-菲咯啉）3 以相同的效力（在微摩尔范围内）杀死 CSCs 和大量癌细胞，这表明它有可能用单剂量去除异质肿瘤群体。令人鼓舞的是，3 还能像广泛使用的抗 CSC 药物萨利霉素一样，抑制乳腺球体的形成。该配合物通过线粒体膜去极化、抑制线粒体代谢和细胞内活性氧 (ROS) 生成来诱导 CSC 凋亡。据我们所知，这是首次研究铱配合物的抗 CSC 特性。
