TY - JOUR
T1 - Design, synthesis and biological evaluation of fluorescent derivatives of ursolic acid in living cells
AU - Mei, Wenyi
AU - Xie, Lijuan
AU - Zhang, Xiaodong
AU - Shi, Cunjian
AU - Wang, Fengzhi
AU - Fu, Qiqi
AU - Zhao, Zhenjiang
AU - Li, Honglin
AU - Xu, Yufang
AU - Chen, Zhuo
N1 - Publisher Copyright:
© 2024
PY - 2024/5
Y1 - 2024/5
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Autophagy
KW - Fluorescent derivatives
KW - Pentacyclic triterpenoid
KW - Ursolic acid
UR - https://www.scopus.com/pages/publications/85188212958
U2 - 10.1016/j.cclet.2023.108825
DO - 10.1016/j.cclet.2023.108825
M3 - 文章
AN - SCOPUS:85188212958
SN - 1001-8417
VL - 35
JO - Chinese Chemical Letters
JF - Chinese Chemical Letters
IS - 5
M1 - 108825
ER -