AUTHOR=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 

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

JOURNAL=Frontiers in Chemistry

VOLUME=11

YEAR=2023

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2023.1191498

DOI=10.3389/fchem.2023.1191498

ISSN=2296-2646

ABSTRACT=<p>Three series of podophyllotoxin derivatives with various nitrogen-containing heterocycles were designed and synthesized. The antitumor activity of these podophyllotoxin derivatives was evaluated <italic>in vitro</italic> against a panel of human tumor cell lines. The results showed that podophyllotoxin-imidazolium salts and podophyllotoxin-1,2,4-triazolium salts <bold>a1–a20</bold> exhibited excellent cytotoxic activity. Among them, <bold>a6</bold> was the most potent cytotoxic compound with IC<sub>50</sub> values of 0.04–0.29 μM. Podophyllotoxin-1,2,3-triazole derivatives <bold>b1–b5</bold> displayed medium cytotoxic activity, and podophyllotoxin-amine compounds <bold>c1–c3</bold> has good cytotoxic activity with IC<sub>50</sub> value of 0.04–0.58 μM. Furthermore, cell cycle and apoptosis experiments of compound <bold>a6</bold> were carried out and the results exhibited that <bold>a6</bold> could induce G2/M cell cycle arrest and apoptosis in HCT-116 cells.</p>