Synthesis and anticancer activity of podophyllotoxin derivatives with nitrogen-containing heterocycles

Frontiers in Chemistry

Chemistry

Yi Yi Myint¹  Yamiao Meng²  Zhiyun Zhu²  Xiaotong Sun²  Jingfeng Zhao²  Meng Yin²  Caimei Zhang²  Lingmei Kong²  Minggao Xue²  Yan Li²  Yongsheng Fang²  Xiaodong Yang² 

[1] Department of Chemistry, University of Mandalay, Mandalay, Myanmar;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;

关键词: podophyllotoxin;    imidazolium salts;    triazoles;    antitumor activity;    structure-activity relationships;   

DOI  :  10.3389/fchem.2023.1191498

 received in 2023-03-22, accepted in 2023-04-21,  发布年份 2023

来源: Frontiers

【 摘 要 】

Three series of podophyllotoxin derivatives with various nitrogen-containing heterocycles were designed and synthesized. The antitumor activity of these podophyllotoxin derivatives was evaluated in vitro against a panel of human tumor cell lines. The results showed that podophyllotoxin-imidazolium salts and podophyllotoxin-1,2,4-triazolium salts a1–a20 exhibited excellent cytotoxic activity. Among them, a6 was the most potent cytotoxic compound with IC50 values of 0.04–0.29 μM. Podophyllotoxin-1,2,3-triazole derivatives b1–b5 displayed medium cytotoxic activity, and podophyllotoxin-amine compounds c1–c3 has good cytotoxic activity with IC50 value of 0.04–0.58 μM. Furthermore, cell cycle and apoptosis experiments of compound a6 were carried out and the results exhibited that a6 could induce G2/M cell cycle arrest and apoptosis in HCT-116 cells.

【 授权许可】

Unknown   
Copyright © 2023 Yin, Fang, Sun, Xue, Zhang, Zhu, Meng, Kong, Myint, Li, Zhao and Yang.