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

• Published in: Frontiers in chemistry Vol. 11; p. 1191498
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 10.05.2023
• Subjects: antitumor activity; Chemistry; imidazolium salts; podophyllotoxin; structure-activity relationships; triazoles; triazoles; podophyllotoxin; structure-activity relationships; antitumor activity; imidazolium salts
• ISSN: 2296-2646; 2296-2646
• DOI: 10.3389/fchem.2023.1191498

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.