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

作　　者：Wenyi Mei Lijuan Xie Xiaodong Zhang Cunjian Shi Fengzhi Wang Qiqi Fu Zhenjiang Zhao Honglin Li Yufang Xu Zhuo Chen 

机构地区：[1]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 [2]Innovation Center for AI and Drug Discovery,East China Normal University,Shanghai 200062,China [3]Lingang Laboratory,Shanghai 200031,China

出　　处：《Chinese Chemical Letters》2024年第5期287-289,共3页中国化学快报（英文版）

基　　金：supported in part by the National Key Research and Development Program of China(No.2022YFC3400501);the National Natural Science Foundation of China(Nos.81825020 and 82150208 to H.L.);the Shanghai Science and Technology Commission Biomedical Science and Technology Support Special Project(Nos.21S11907900 and 20S11901000 to Z.Z.);sponsored by the National Program for Special Supports of Eminent Professionals;the National Program for Support of Top-Notch Young Professionals.

摘　　要：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(IC_(50))=9.21±0.50μmol/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.

关 键 词：Pentacyclic triterpenoid Ursolic acid Fluorescent derivatives AUTOPHAGY APOPTOSIS 

分 类 号：O657.3[理学—分析化学] TQ460.1[理学—化学] Q503[化学工程—制药化工]