5-O-Caffeoylquinic acid methyl ester

5-O-Methyl caffeoylquinic acid (methyl neochlorogenic acid, CAS No.: 123410-65-1) is a caffeoylquinic acid derivative derived from Lonicera japonica (honeysuckle). When used alone, it shows no significant toxicity to liver cancer cells (such as HepG2). However, when combined with glycolysis inhibitors such as 2-deoxy-D-glucose (2-DG) and 3-bromopyruvate (3-BP), it can enhance the inhibitory effect on liver cancer cell proliferation by 1.5–3 times (more pronounced under low-glucose conditions). This is achieved by inhibiting HKII to block glucose phosphorylation and inhibiting PKM2 to reduce pyruvate production, thereby weakening the Warburg effect (aerobic glycolysis) in liver cancer cells, reducing ATP and ROS production. At the same time, the combination can block the activation of the ROS-GLUT1/3 signaling axis induced by these inhibitors, effectively delaying the development of drug resistance in liver cancer cells[1]. Due to methyl esterification, 5-O-methyl caffeoylquinic acid loses its free carboxyl group, resulting in the loss of in vitro anti-HBV activity[2].

References：

[1] Hunan Agricultural University, Wenzhou Medical University. A pharmaceutical composition for reducing drug resistance in liver cancer cells and its application: CN202111179728.1[P]. 2022-05-13.

[2] Ge L, Wan H, Tang S, Chen H, Li J, Zhang K, Zhou B, Fei J, Wu S, Zeng X. Novel caffeoylquinic acid derivatives from Lonicera japonica Thunb. flower buds exert pronounced anti-HBV activities. RSC Adv. 2018 Oct 15;8(62):35374-35385. doi: 10.1039/c8ra07549b. PMID: 35547940; PMCID: PMC9088017.