Inorg Chem. 2019 Feb 4;58(3):2208-2217. doi: 10.1021/acs.inorgchem.8b03447. Epub 2019 Jan 24.
Subtle ligand modifications on ruthenium arene complexes can lead to different mechanisms of action and result in significant changes in the anticancer efficacy. Herein, four novel dinuclear ruthenium(II) arene complexes were designed and prepared. In vitro tests indicated that complexes 1-3 displayed moderate antiproliferative activity against the tested cancer cells, while the cytotoxicity of complex 4 is superior or comparable to that of cisplatin. Further studies indicated that complexes 1-4 induce cell death through DNA interaction and a reactive-oxygen-species-mediated endoplasmic reticulum (ER) stress pathway, which is the first example of an organometallic ruthenium(II) arene complex to induce ER stress as well as DNA interaction. This kind of dinuclear ruthenium(II) arene complex has unique biological characteristics and is a promising model for new anticancer drug development.
芳基金属钌配合物的细微配体修饰可以导致不同的作用机制，并导致抗癌疗效的显著变化。在此，设计并制备了四个新型双核钌（II）芳基金属配合物。体外测试表明，配合物 1-3 对测试的癌细胞表现出中等的增殖抑制活性，而配合物 4 的细胞毒性优于或与顺铂相当。进一步的研究表明，配合物 1-4 通过 DNA 相互作用和活性氧介导的内质网（ER）应激途径诱导细胞死亡，这是首例有机金属钌（II）芳基金属配合物诱导 ER 应激以及 DNA 相互作用的例子。这种双核钌（II）芳基金属配合物具有独特的生物学特性，是开发新型抗癌药物的有前途的模型。
