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

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

doi:10.3389/fchem.2022.951713

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

Front Chem. 2022 Sep 7:10:951713. doi: 10.3389/fchem.2022.951713. eCollection 2022.

Authors

Affiliation

¹ Key Laboratory of Natural Medicines of the Changbai Mountain, Affifiliated Ministry of Education, College of Pharmacy, Yanbian University, Jilin, China.

Abstract

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 in vitro. Some of the tested derivatives showed improved antiproliferative activity compared to the lead compound, quillaic acid. Among them, compound E (IC₅₀ = 2.46 ± 0.44 μM) showed the strongest antiproliferative activity against HCT116 cells; compared with quillaic acid (IC₅₀ > 10 μM), its efficacy against HCT116 cancer cells was approximately 4-fold higher than that of quillaic acid. Compound E also induces cell cycle arrest and apoptosis by modulating NF-κB and MAPK pathways. Therefore, the development of compound E is certainly valuable for anti-tumor applications.

Keywords: Western blot; antitumor; apoptosis; cell-cycle arrest; quillaic acid.