AUTHOR=Huang Xing , Zhang Chang-Hao , Deng Hao , Wu Dan , Guo Hong-Yan , Lee Jung Joon , Chen Fen-Er , Shen Qing-Kun , Jin Li-Li , Quan Zhe-Shan 

TITLE=Synthesis and evaluation of anticancer activity of quillaic acid derivatives: A cell cycle arrest and apoptosis inducer through NF-κB and MAPK pathways

JOURNAL=Frontiers in Chemistry

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2022.951713

DOI=10.3389/fchem.2022.951713

ISSN=2296-2646

ABSTRACT=<p>A series of quillaic acid derivatives with different substituents on the 28-carboxyl group were designed and synthesized. Five human cancer cell lines (HCT116, BEL7402, HepG2, SW620, and MCF-7) were evaluated for their antitumor activity <italic>in vitro.</italic> Some of the tested derivatives showed improved antiproliferative activity compared to the lead compound, quillaic acid. Among them, compound <bold>E</bold> (IC<sub>50</sub> = 2.46 ± 0.44 μM) showed the strongest antiproliferative activity against HCT116 cells; compared with quillaic acid (IC<sub>50</sub> &gt; 10 μM), its efficacy against HCT116 cancer cells was approximately 4-fold higher than that of quillaic acid. Compound <bold>E</bold> also induces cell cycle arrest and apoptosis by modulating NF-κB and MAPK pathways. Therefore, the development of compound <bold>E</bold> is certainly valuable for anti-tumor applications.</p>