Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
J Am Chem Soc. 2013 Sep 25;135(38):14060-3. doi: 10.1021/ja4075375. Epub 2013 Sep 16.
The cellular response evoked by antiproliferating osmium(VI) nitrido compounds of general formula OsN(N^N)Cl3 (N^N = 2,2'-bipyridine 1, 1,10-phenanthroline 2, 3,4,7,8-tetramethyl-1,10-phenanthroline 3, or 4,7-diphenyl-1,10-phenanthroline 4) can be tuned by subtle ligand modifications. Complex 2 induces DNA damage, resulting in activation of the p53 pathway, cell cycle arrest at the G2/M phase, and caspase-dependent apoptotic cell death. In contrast, 4 evokes endoplasmic reticulum (ER) stress leading to the upregulation of proteins of the unfolded protein response pathway, increase in ER size, and p53-independent apoptotic cell death. To the best of our knowledge, 4 is the first osmium compound to induce ER stress in cancer cells.
通过对通式为 OsN(N^N)Cl3 的具有抗增殖作用的锇(VI)亚硝化物(N^N = 2,2'-联吡啶 1、1,10-菲咯啉 2、3,4,7,8-四甲基-1,10-菲咯啉 3 或 4,7-二苯基-1,10-菲咯啉 4)进行细微的配体修饰,可以调节细胞的反应。配合物 2 诱导 DNA 损伤,导致 p53 途径激活、细胞周期停滞在 G2/M 期和 caspase 依赖性细胞凋亡。相比之下,4 会引起内质网 (ER) 应激,导致未折叠蛋白反应途径的蛋白质上调、ER 大小增加和 p53 非依赖性细胞凋亡。据我们所知,4 是第一个在癌细胞中诱导 ER 应激的锇化合物。