Identification of a novel 10-hydroxyevodiamine prodrug as a potent topoisomerase inhibitor with improved aqueous solubility for treatment of hepatocellular carcinoma
文献类型：期刊论文
| 作者 | Wei, Xiuzhen; Zhang, Xi; Peng, Yan; Wu, Junbo; Mo, Hanxuan; An, Zhigang; Deng, Xinyu; Peng, Ying; Liu, Linyi; Jiang, Weifan |
| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2024 |
| 卷号 | 279 |
| 英文摘要 | Natural product evodiamine (Evo) and its synthetic derivatives represent an attractive dual Topo 1/2 inhibitors with broad-spectrum antitumor efficacy. However, the clinical applications of these compounds have been impeded by their poor aqueous solubility. Herein, a series of water-soluble 10-substituted-N(14)-phenylevodiamine derivatives were designed and synthesized. The most potent compound 45 featuring a quaternary ammonium salt fragment achieved robust aqueous solubility and nanomolar potency against a panel of human hepatoma cell lines Huh7, HepG2, SK-Hep-1, SMMC-7721, and SMMC-7721/DOX (doxorubicin-resistant cell). Further studies revealed that 45 could inhibit Topo 1 and Topo 2, induce apoptosis, arrest the cell cycle at the G2/M stage and inhibit the migration and invasion. Compound 45 exhibited potent antitumor activity (TGI = 51.1 %, 10 mg/kg) in the Huh7 xenograft model with acceptable safety profile. In addition, a 21-day long-term dose toxicity study confirmed that the maximum tolerated dose of compound 45 was 20 mg/kg. Overall, this study presented a promising Evo-derived candidate for the treatment of hepatocellular carcinoma. |
| 源URL | [http://210.75.249.4/handle/363003/61956]  |
| 专题 | 西北高原生物研究所_中国科学院西北高原生物研究所 |
| 推荐引用方式 GB/T 7714 | Wei, Xiuzhen,Zhang, Xi,Peng, Yan,et al. Identification of a novel 10-hydroxyevodiamine prodrug as a potent topoisomerase inhibitor with improved aqueous solubility for treatment of hepatocellular carcinoma[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2024,279. |
| APA | Wei, Xiuzhen.,Zhang, Xi.,Peng, Yan.,Wu, Junbo.,Mo, Hanxuan.,...&Zhuo, Linsheng.(2024).Identification of a novel 10-hydroxyevodiamine prodrug as a potent topoisomerase inhibitor with improved aqueous solubility for treatment of hepatocellular carcinoma.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,279. |
| MLA | Wei, Xiuzhen,et al."Identification of a novel 10-hydroxyevodiamine prodrug as a potent topoisomerase inhibitor with improved aqueous solubility for treatment of hepatocellular carcinoma".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 279(2024). |
入库方式： OAI收割
来源：西北高原生物研究所
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