Preparation And Structure-activity Relationship Of Lupine Triterpenes With The Selective Inhibitory Activity For The Glioma Stem Cells

This thesis consists of five parts:The first chapter provides an overview of the research on active substances and the current treatment methods for glioma;The second chapter describes in detail the targeted isolation of more natural triterpenoids of the lupeol-type from the bark of Canarium album,an olive plant,using HPLC-UV,1D NMR,and LC-MS/MS,and the enrichment of compounds with high content;The third chapter synthesizes various natural lupeol-type triterpenoids through reasonable drug synthesis design,using lupeol and betulin as substrates;The fourth chapter evaluates the anti-glioma activity of obtained natural lupeol-type triterpenoids and modified natural lupeol-type triterpenoids,and discusses the structure-activity relationship of selective anti-glioma stem cell activity based on the activity results;The fifth chapter summarizes the work done in this thesis and discusses the results.The results are as follows:（1）By using LC-MS and HPLC-UV,ten natural lupeol-type triterpenoids were obtained from the bark of Canarium album,an olive plant,and high-content components,lupeol（38.9 g）and betulin（1.45 g）,were enriched through silica gel column chromatography,reversed-phase medium pressure,Sephadex HL-20 gel column,and high-performance liquid chromatography.（2）A total of 51 lupeol-type triterpenoids were synthesized by using reasonable design of synthetic route and structural modification with lupeol and betulin as substrates.（3）The obtained natural and modified lupeol-type compounds were evaluated for their anti-glioma activity.It was found that compounds B29,B32,B35,B37,B40,and B52 had specific killing activity against Brain glioma stem cells（3#-CSC）,and compounds B30,B31,and B36 could kill glioma cells（U251）and glioma stem cells.The IC₅₀ value of B32 was measured to be 3.96μM,while the IC₅₀ value of lupeol20.95μM.This thesis shows that the C-3 salt product of lupeol has good activity after structural modification,and the terminal double bond of lupeol has a significan.The results of this paper show that the C-3 salt product has good activity after structural modification of lupeol.The terminal double bond of lupeol has a great influence on the activity,and its activity may be determined by two positions.To a certain extent,this study clarified the structure-activity relationship of lupeane-type triterpenoids in the selective inhibition of glioma stem cells,and provided a theoretical basis for the further study of the selective inhibition of glioma stem cells by these compounds.