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首页> 外文期刊>Dalton transactions: An international journal of inorganic chemistry >Fluorescent iridium(III) coumarin-salicylaldehyde Schiff base compounds as lysosome-targeted antitumor agents
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Fluorescent iridium(III) coumarin-salicylaldehyde Schiff base compounds as lysosome-targeted antitumor agents

机译：荧光铱（III）香豆素 - 水杨醛席史基苯基碱化合物作为溶酶体靶向抗肿瘤剂

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摘要

Six fluorescent half-sandwich iridium(s) coumarin-salicylaldehyde Schiff base (O<^>N) compounds ([(eta(5)-Cp*)Ir(O<^>N)Cl) were prepared and characterized. The introduction of a coumarin unit increased the antitumor activity (IC50: 9.9 +/- 0.1 mu M-40.7 +/- 12.9 mu M) of these compounds, the best of which was nearly two times that of clinical cisplatin. The results of laser confocal microscopy demonstrated that these compounds possessed an energy-dependent cellular uptake mechanism, accumulated in the lysosomes (Pearson co-localization coefficient: similar to 0.7), damaged the integrity of the lysosomes, and induced apoptosis. The compounds could also decrease the mitochondrial membrane potential, catalyze the oxidation of the coenzyme (nicotinamide-adenine dinucleotide) and improve the levels of the intracellular reactive oxygen species, following an antitumor mechanism of oxidation. Additionally, these compounds could block the metastasis of tumor cells. Above all, these iridium(III) compounds show potential as antitumor agents with dual functions: lysosomal damage and anti-metastasis.
机译：六个荧光半三明治铱（S）香豆素 - 水杨醛席夫碱（O <^> N）化合物（[（η（5）-CP *）IR（O <^> N）CL）并表征。香豆素单位的引入增加了这些化合物的抗肿瘤活性（IC50：9.9 +/- 0.1 mu M-40.7 +/-12.9μm），其中最佳是临床顺铂的近两倍。激光共聚焦显微镜的结果证明，这些化合物具有积聚在溶酶体中的能量依赖性蜂窝摄取机制（Pearson共定系数：类似于0.7），损坏溶酶体的完整性，并诱导细胞凋亡。该化合物还可以降低线粒体膜电位，催化辅酶（烟酰胺 - 腺嘌呤二核苷酸）的氧化，并在氧化抗肿瘤机制后改善细胞内反应性氧物种的水平。另外，这些化合物可以阻断肿瘤细胞的转移。最重要的是，这些铱星（III）化合物显示出具有双重功能的抗肿瘤剂：溶酶体损伤和抗转移。

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