Synthesis, Biological Evaluation of Fluorescent 23-Hydroxybetulinic Acid Probes, and Their Cellular Localization Studies

Yao, Hong; Wei, Guoxiang; Liu, Yanpeng; Yao, Hequan; Zhu, Zheying; Ye, Wencai; Wu, Xiaoming; Xu, Jinyi; Xu, Shengtao

Abstract

© 2018 American Chemical Society. 23-Hydroxybetulinic acid (23-HBA) is a complex lupane triterpenoid, which has attracted increasing attention as an anticancer agent. However, its detailed mechanism of anticancer action remains elusive so far. To reveal its anticancer mode of action, a series of fluorescent 23-HBA derivatives conjugated with coumarin dyes were designed, synthesized, and evaluated for their antiproliferative activities. Subcellular localization and uptake profile studies of representative fluorescent 23-HBA probe 26c were performed in B16F10 cells, and the results suggested that probe 26c was rapidly taken up into B10F10 cells in a dose-dependent manner and mitochondrion was the main site of its accumulation. Further mode of action studies implied that the mitochondrial pathway was involved in 23-HBA-mediated apoptosis. Together, our results provided new clues for revealing the molecular mechanism of natural product 23-HBA for its further development into an antitumor agent.

Citation

Yao, H., Wei, G., Liu, Y., Yao, H., Zhu, Z., Ye, W., Wu, X., Xu, J., & Xu, S. (2018). Synthesis, Biological Evaluation of Fluorescent 23-Hydroxybetulinic Acid Probes, and Their Cellular Localization Studies. ACS Medicinal Chemistry Letters, 9(10), 1030-1034. https://doi.org/10.1021/acsmedchemlett.8b00321

• Journal Article Type: Article
• Acceptance Date: Sep 25, 2018
• Online Publication Date: Sep 25, 2018
• Publication Date: Oct 11, 2018
• Deposit Date: Dec 5, 2018
• Publicly Available Date: Sep 26, 2019
• Journal: ACS Medicinal Chemistry Letters
• Electronic ISSN: 1948-5875
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 10
• Pages: 1030-1034
• DOI: https://doi.org/10.1021/acsmedchemlett.8b00321
• Public URL: https://nottingham-repository.worktribe.com/output/1370824
• Publisher URL: https://pubs.acs.org/doi/10.1021/acsmedchemlett.8b00321
• Contract Date: Dec 6, 2018