Citation: Wenyi Mei, Lijuan Xie, Xiaodong Zhang, Cunjian Shi, Fengzhi Wang, Qiqi Fu, Zhenjiang Zhao, Honglin Li, Yufang Xu, Zhuo Chen. Design, synthesis and biological evaluation of fluorescent derivatives of ursolic acid in living cells[J]. Chinese Chemical Letters, ;2024, 35(5): 108825. doi: 10.1016/j.cclet.2023.108825 shu

Design, synthesis and biological evaluation of fluorescent derivatives of ursolic acid in living cells

Wenyi Mei ^{a, 1} ,
Lijuan Xie ^{a, 1} ,
Xiaodong Zhang ^a ,
Cunjian Shi ^a ,
Fengzhi Wang ^a ,
Qiqi Fu ^a ,
Zhenjiang Zhao ^a ,
Honglin Li ^{a, b, c, *,} ,
Yufang Xu ^{a, *,} ,
Zhuo Chen ^{a, *,}

a.
Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
b.
Innovation Center for AI and Drug Discovery, East China Normal University, Shanghai 200062, China
c.
Lingang Laboratory, Shanghai 200031, China

hlli@ecust.edu.cn

yfxu@ecust.edu.cn

chenzhuo@ecust.edu.cn

Received Date: 9 May 2023
Revised Date: 17 July 2023
Accepted Date: 18 July 2023
Available Online: 20 July 2023

Figures(3)

Ursolic acid (UA) is a naturally occurring ursane triterpenoid, which exhibits a wide range of unique biological activities. To clarify its mechanism of action (MOA), a series of fluorescent derivatives of UA (5a–c) were designed and synthesized by conjugation with 7-nitrobenzo-2-oxa-1,3-diazole (NBD) fluorophore. Among them, 5c exhibited similar anti-proliferative activity with UA against HCT116 cells (half maximal inhibitory concentration (IC₅₀) = 9.21 ± 0.50 µmol/L). Cell imaging experiment indicated that 5c was rapidly taken up in HCT116 cells in a dose and time-dependent manner. Then, 5c was found to localize in endoplasmic reticulum (ER), lysosomes, and mitochondria, but not in nucleus of HCT116 cells by confocal microscopy studies. Preliminary MOA proved that UA induced autophagy with a unique intracellular distribution mechanism involving ER and lysosome. In all, our work provides new clues for revealing the molecular mechanism of UA as an antitumor agent.
- Pentacyclic triterpenoid,
- Ursolic acid,
- Fluorescent derivatives,
- Autophagy,
- Apoptosis
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