| 双核芳基Os(Ⅱ)配合物的合成及诱导肿瘤铁死亡机制 | |
| Synthesis and anticancer mechanism of ferroptosis of binuclear Os(Ⅱ)-arene complex | |
| 摘要: 本文报道了一种双核锇Os(Ⅱ)配合物[Os (η6-bip)(1，3-bib) Cl]2Cl2(bib-Os)，其中η6-bip=η6-联苯，1，3-bib=1，3-二(1H-咪唑-1-基)苯。并通过1H NMR和ESI-MS进行基础表征。配合物bib-Os具有良好的脂溶性，易在细胞中积累。配合物bib-Os对人卵巢癌A2780细胞表现出高效的抗增殖活性，可产生活性氧(ROS)并诱导线粒体损伤。脂质过氧化物(LPO)积累、谷胱甘肽(GSH)消耗和谷胱甘肽过氧化物酶4(GPX4)下调表明，配合物bib-Os诱导A2780细胞死亡的主要机制是铁死亡，bib-Os是第一例诱导肿瘤细胞铁死亡的Os金属配合物。 | |
| 关键词: 芳基Os(Ⅱ)配合物 双核 线粒体损伤 铁死亡 | |
| 基金项目: 国家自然科学基金(No.21771109，22077066，21807060)资助。 | |
| Abstract: Here, we describe [Os(η6-bip)(1,3-bib)Cl]2Cl2 (bib-Os) (η6-bip=η6-biphenyl, 1,3-bib=1,3-di(1H-imidazol-1-yl) benzene), a binuclear Os(Ⅱ) complex, which was characterized by 1H NMR and ESI-MS. The results showed that complex bib-Os had good lipophilicity (lg Po/w=1.52) and was easy to accumulate in cells. Complex bib-Os showed high antiproliferative activity against human ovarian A2780 cancer cells (IC50=4.2 μmol·L-1), producing a large number of reactive oxygen species (ROS) and inducing mitochondrial morphological damage and membrane potential decline. Lipid peroxide (LPO) accumulation, glutathione (GSH) depletion, and glutathione peroxidase 4 (GPX4) inhibition further verified bib-Os-induced cell death through the ferroptosis pathway. | |
| Keywords: Os(Ⅱ)-arene complex binuclear mitochondrial damage ferroptosis | |
| 投稿时间：2023-04-19 修订日期：2023-09-06 | |
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| 郭冰莲,李季,吕梦迪,薛旭玲,刘红科.双核芳基Os(Ⅱ)配合物的合成及诱导肿瘤铁死亡机制[J].无机化学学报,2023,39(10):1887-1897. | |
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| Support information: 相关附件： 230151_双核芳基Os(II)配合物的合成及诱导肿瘤铁死亡机制研究_支持信息.doc | |
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