Activation of C-H bonds in nitrones leads to iridium hydrides with antitumor activity.
Activation of C-H bonds in nitrones leads to iridium hydrides with antitumor activity.
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DOI：
10.1021/jm4004973
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发表时间：
2013-08
影响因子：
7.3
通讯作者：
Xiaoda Song;Yong Qian;R. Ben;Xiang-Yong Lu;Hailiang Zhu;Hui Chao;Jing Zhao-
中科院分区：
文献类型：
--
作者：
Xiaoda Song;Yong Qian;R. Ben;Xiang-Yong Lu;Hailiang Zhu;Hui Chao;Jing Zhao-
本文报道了一系列由芳香硝酮C-H键活化而成的新型环化铱配合物的设计、合成及其抗肿瘤活性的生物学评价。硝酮配体基于流行的抗氧化剂α-苯基-N-叔丁基硝酮（PBN）的结构。与顺铂相比，铱配合物对HepG 2细胞具有良好的抗肿瘤活性。选择具有最有效抗癌活性的金属配位化合物2f进行进一步分析，因为其能够诱导细胞凋亡并与DNA相互作用。在癌症研究所（Institute of Cancer Research，ICR）小鼠的肿瘤异种移植模型的体外研究和体内功效分析期间，络合物2f表现出显著上级顺铂的抗肿瘤活性。我们的研究结果首次表明，金属配合物可能是一种新型的金属基抗肿瘤剂。
We report the design and synthesis of a series of new cyclometalated iridium hydrides derived from the C-H bond activation of aromatic nitrones and the biological evaluation of these iridium hydrides as antitumor agents. The nitrone ligands are based on the structure of a popular antioxidant, α-phenyl-N-tert-butylnitrone (PBN). Compared to cisplatin, the iridium hydrides exhibit excellent antitumor activity on HepG2 cells. The metal-coordinated compound with the most potent anticancer activity, 2f, was selected for further analysis because of its ability to induce apoptosis and interact with DNA. During in vitro studies and in vivo efficacy analysis with tumor xenograft models in Institute of Cancer Research (ICR) mice, complex 2f exhibited antitumor activity that was markedly superior to that of cisplatin. Our results suggest, for the first time, that metal hydrides could be a new type of metal-based antitumor agent.