Activation of C鈥揌 Bonds in Nitrones Leads to Iridium Hydrides with Antitumor Activity

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• 作者：Xiaoda Song ; Yong Qian ; Rong Ben ; Xiang Lu ; Hai-Liang Zhu ; Hui Chao ; Jing Zhao
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：August 22, 2013
• 年：2013
• 卷：56
• 期：16
• 页码：6531-6535
• 全文大小：251K
• 年卷期：v.56,no.16(August 22, 2013)
• ISSN：1520-4804

文摘

We report the design and synthesis of a series of new cyclometalated iridium hydrides derived from the C鈥揌 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, 伪-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.