3-(2-吡啶-3-乙烯基)-1H-吲哚钌配合物的合成及抗肿瘤性能

以3-(2-吡啶-3-乙烯基)-1H-吲哚(Indole)为配体与二联吡啶钌前体Ru(bpy)₂Cl₂进行配位反应,得到一种新型联吡啶钌配合物Ru-Indole,并通过1H NMR、ESI-MS及元素分析对配体及配合物进行了表征。研究结果表明,配合物具有良好的脂溶性,使得药物能够顺利地进入细胞内,克服了钌类配合物脂溶性差的特点。进一步使用MTT法、流式细胞术、共聚焦成像及蛋白免疫印迹法对Ru-Indole的抗肿瘤活性及诱导肿瘤细胞死亡的机制进行了深入的探究。结果发现,Ru-Indole与配体Indole及前体Ru(bpy)₂Cl₂相比表现出良好的抗肿瘤活性,表明引入的吲哚配体提高了配合物的脂溶性,提高了配合物的细胞摄取量,最终有效提高了配合物的细胞毒性。同时通过共聚焦显微镜及电感耦合等离子体质谱(ICP-MS)发现Ru-Indole富集在肿瘤细胞的线粒体和溶酶体中,通过线粒体通路诱导线粒体膜电位的改变,并通过细胞自噬的方式诱导细胞死亡。

Synthesis and Antitumor Properties of 3-(2-Pyridine-3-vinyl)-1H-indole Dipyridine Ruthenium Complex

In this work, we designed a novel bipyridine ruthenium complex Ru-Indole using 3-(2-pyridine-3-vinyl)¹H-indoles (Indole) as the ligand with the bipyridine ruthenium precursor Ru(bpy)₂Cl₂ as the coordination linkage. The structures of ligand and related complexes were characterized by using ¹H NMR, ESI-MS and elemental analysis. Using a fluorescence spectrophotometer and an ultraviolet-visible spectrophotometer, it is found that the complex could emit fluorescence under the excitation of UV-Vis light, which realized the visual imaging of the complex in the cell. The introduction of the ligand greatly improved the lipophilicity of the complex Ru-Indole, rendering it to be easier to enter the cell and exhibited better anti tumor activity compared with the ligand Indole and the precursor Ru(bpy)₂Cl₂. Furthermore, we used flow cytometry, confocal imaging and western blotting to explore the cell death mechanism induced by Ru-Indole. The results show that the complex Ru-Indole could be enriched in the mitochondria and lysosomes of tumor cells, and could change the mitochondrial membrane potential and at last induce the autophagy.