可点击抗癌铱催化剂的成像。
Imaging of a clickable anticancer iridium catalyst.
机构信息
State Key Laboratory of Coordination Chemistry, Institute of Chemistry and BioMedical Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.
Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Biofunctional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China.
出版信息
J Inorg Biochem. 2018 Mar;180:179-185. doi: 10.1016/j.jinorgbio.2017.12.019. Epub 2017 Dec 29.
Iridium-based anticancer reagents are receiving increasing attention for their high cytotoxicity. Herein, by activating CH 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.
基于铱的抗癌试剂因其高细胞毒性而受到越来越多的关注。在此，我们通过激活广为人知的抗氧化剂α-苯基-N-叔丁基硝酮（PBN）中的 CH 键，合成并表征了一系列新型铱配合物。配合物 1-AMP 对人卵巢癌细胞 A2780 表现出最佳的增殖抑制活性。配合物 1-AMP 中的叠氮基团经历了铜（I）催化的叠氮-炔环加成（CuAAC）反应，并且细胞内的荧光成像表明它主要积累在线粒体中。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应变促进的炔-叠氮环加成（SPAAC）反应使配合物 1-AMP 与一种商业化染料发生反应，证实其主要靶向线粒体。含有硝酮配体和叠氮基团的基于铱的抗癌配合物可能为探究金属药物的机制提供了一种有用的工具。
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