Yin Meng, Fang Yongsheng, Sun Xiaotong, Xue Minggao, Zhang Caimei, Zhu Zhiyun, Meng Yamiao, Kong Lingmei, Myint Yi Yi, Li Yan, Zhao Jingfeng, Yang Xiaodong
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Provincial Center for Research & Development of Natural Products, School of Pharmacy, Yunnan University, Kunming, China.
Department of Chemistry, University of Mandalay, Mandalay, Myanmar.
Front Chem. 2023 May 10;11:1191498. doi: 10.3389/fchem.2023.1191498. eCollection 2023.
Three series of podophyllotoxin derivatives with various nitrogen-containing heterocycles were designed and synthesized. The antitumor activity of these podophyllotoxin derivatives was evaluated against a panel of human tumor cell lines. The results showed that podophyllotoxin-imidazolium salts and podophyllotoxin-1,2,4-triazolium salts exhibited excellent cytotoxic activity. Among them, was the most potent cytotoxic compound with IC values of 0.04-0.29 μM. Podophyllotoxin-1,2,3-triazole derivatives displayed medium cytotoxic activity, and podophyllotoxin-amine compounds has good cytotoxic activity with IC value of 0.04-0.58 μM. Furthermore, cell cycle and apoptosis experiments of compound were carried out and the results exhibited that could induce G2/M cell cycle arrest and apoptosis in HCT-116 cells.
设计并合成了具有各种含氮杂环的三类鬼臼毒素衍生物。针对一组人类肿瘤细胞系评估了这些鬼臼毒素衍生物的抗肿瘤活性。结果表明，鬼臼毒素 - 咪唑鎓盐和鬼臼毒素 - 1,2,4 - 三唑鎓盐表现出优异的细胞毒性活性。其中，是最具细胞毒性的化合物，IC值为0.04 - 0.29 μM。鬼臼毒素 - 1,2,3 - 三唑衍生物表现出中等细胞毒性活性，鬼臼毒素 - 胺类化合物具有良好的细胞毒性活性，IC值为0.04 - 0.58 μM。此外，对化合物进行了细胞周期和凋亡实验，结果表明该化合物可诱导HCT - 116细胞发生G2/M期细胞周期阻滞和凋亡。
