Design,Synthesis And Pharmacological Activity Of Oleanolic Acid Benzyl Derivatives

Oleanolic acid has many good pharmacological effects,such as anti-cancer,anti-inflammatory,anti-bacterial,kidney-protecting,anti-diabetes,anti-oxidation and so on.Our group has been committed to the structural modification of pentacyclic triterpenoids,and strives to obtain anticancer prodrugs with good anticancer effects,high bioavailability,and development and development prospects.In this paper,oleanolic acid was selected as the parent body,and it was rationally modified according to the experience of the predecessors.The characterization and activity of the synthetic materials were mainly composed of the three parts below:It is introducing the pharmacological activity,progress of research and development prospects of OA in the first part;And the second part is introducing that a series of OA derivatives were designed and synthesized.OA reacted to form benzyl ester.A total of 23 compounds were synthesized and 18 new compounds were obtained.The structures of them were characterized by 1H NMR and carbon spectra.The third part shows the anti-cancer activity of OA and its derivatives.Via MTT method,the OA benzyl ester derivatives,fluoroformyl benzyl ester derivatives and benzyloxybenzyl ester derivatives are tested respectively.Human breast cancer cells:MDA-MB-231,human lung cancer cells:A549 and human bronchial epithelial cells:2B inhibitory activity.According to the results,comparing to the commercially available anticancer drug doxorubicin,Compound 14 showed higher anticancer activity,and its safety was also higher than that of the anticancer drug doxorubicin;Compound 1 had some inhibition on human breast cancer cells.Function;Compound 20 has high safety to human body and inhibits human breast cancer cells.In addition,Compound 14 was found to induce apoptosis in human lung cancer cells by Annexin V-PI double staining.MDA-MB-231 breast cancer cells were treated with compound 14 at different concentrations(0 ?M as control,2?M,4?M and 8?M)for 24 h,and then the MNE-MB-231 breast cancer cell nucleus was double-stained with Annexin V-PI.The apoptosis was detected.With the increase of the concentration of compound 14,the apoptosis rate of MDA-MB-231 breast cancer cells was significantly increased(after treatment for 24 h,the apoptosis rate was 4.84%,14.3%,26.96%,56.33%).According to the data,it was found that Compound 14 has a remarkable effect of promoting tumor cell apoptosis.Through the research in this thesis,the structural modification and activity modification of the oleanolic acid derivatives have been further explored,and the compounds with good anticancer effect have been found,which has great application prospects.And provide new evidence and perspective for further modification.