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., …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
• Print ISSN: 1948-5875
• 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