Imaging of a clickable anticancer iridium catalyst.
Imaging of a clickable anticancer iridium catalyst.
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DOI：
10.1016/j.jinorgbio.2017.12.019
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发表时间：
2018-03
影响因子：
3.9
通讯作者：
Xiuxiu Wang;Mingli Zhu;F. Gao;Wei Wei-Wei;Yong Qian;Hongke Liu;Jing Zhao
中科院分区：
文献类型：
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作者：
Xiuxiu Wang;Mingli Zhu;F. Gao;Wei Wei-Wei;Yong Qian;Hongke Liu;Jing Zhao
Ir基抗癌试剂因其高度的细胞毒性而受到越来越多的关注。在这里，我们通过激活著名抗氧剂α-苯基-N-叔丁基硝酮中的单键H键，合成并表征了一系列新的Ir络合物。络合物1-AMP对人卵巢癌A2780细胞具有最强的抗增殖活性。配合物1-AMP中的叠氮基发生了铜(I)催化的叠氮化、−和炔环加成反应，细胞内的荧光成像结果表明它主要积聚在线粒体中。相比之下，为了消除铜(I)催化剂的细胞毒性，我们在活细胞中通过菌株促进的炔叠氮环加成(SPAAC)反应，将络合物1-AMP与一种商品化的染料进行了反应，证实了其主要靶向于线粒体。含硝酮配体和叠氮基的Ir基抗癌化合物可能为探索金属药物的作用机制提供了有用的工具。
Iridium-based anticancer reagents are receiving increasing attention for their high cytotoxicity. Herein, by activating Csingle bondH bonds in the well-known antioxidant α-phenyl-N-tert-butylnitrone (PBN), we synthesized and characterized a series of new iridium complexes. Complex 1-AMP exhibited the best antiproliferation activity towards human ovarian cancer A2780 cells. The azide group in complex 1-AMP underwent the Cu(I)-catalysed azide − alkyne cycloaddition (CuAAC) reaction and the resulting fluorescent imaging in cells suggested it mainly accumulated in mitochondria. In comparison, to eliminate cytotoxicity of Cu(I) catalyst, we conducted a reaction between complex 1-AMP and a commercialized dye via strain-promoted alkyne–azide cycloaddition (SPAAC) reaction in live cells, confirming its targeting mainly in the mitochondria. Iridium-based anticancer complexes containing a nitrone ligand and azide group may offer a useful tool to probe the mechanism of metallodrugs.