| 3-(2-吡啶-3-乙烯基)-1H-吲哚钌配合物的合成及抗肿瘤性能 | |
| Synthesis and Antitumor Properties of 3-(2-Pyridine-3-vinyl)-1H-indole Dipyridine Ruthenium Complex | |
| 摘要: 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。 | |
| 关键词: 联吡啶钌配合物 吲哚衍生物 抗肿瘤 线粒体通路 自噬 | |
| 基金项目: 国家自然科学基金（No.21771109，22077066，21807060）和中国博士后基金（No.2019M651874）资助。 | |
| Abstract: 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. | |
| Keywords: bipyridine ruthenium complex indole derivatives antitumor mitochondrial pathway autophagy | |
| 投稿时间：2020-11-13 修订日期：2021-01-05 | |
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| 钱晓婷,吕梦迪,王裙,陶钦,薛旭玲,刘红科.3-(2-吡啶-3-乙烯基)-1H-吲哚钌配合物的合成及抗肿瘤性能[J].无机化学学报,2021,37(5):824-834. | |
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