Design,Synthesis And Antitumor Activity Of Lead Compounds Based On 18?-Glycyrrhetinic Acid

Tumor refers to uncontrolled cell proliferation and is one of the leading causes of human death.Over the years,more and more medical workers have been working on the development of anti-cancer drugs.Structural modification of natural products is a more convenient and efficient method than traditional high-throughput screening,by which highly active,low-toxic anticancer drugs can be obtained.18p-glycyrrhetinic acid is a pentacyclic triterpenoid extracted from the rhizome of natural plant licorice.Studies have shown that glycyrrhetinic acid has a wide range of pharmacological activities,such as:anti-tumor,anti-inflammatory,anti-viral,anti-oxidation,liver protection,anti-allergy and so on.However,due to the low activity of 18-glycyrrhetinic acid,a large number of structural modifications have been made to obtain highly active lead compounds.The research work in this paper mainly includes four parts:The first part:This part firstly summarizes the basic physical and chemical properties,pharmacological activities and structural modifications of 18?-glycyrrhetinic acid,then introduces the basis of the research,the purpose and significance of the research,and the innovation of the article.Part II:This part mainly designed and synthesized four small classes of glycyrrhetinic acid derivatives,including glycyrrhetinic acid 4-benzyloxybenzyl ester,3-oxoglycyrrhetinic acid benzyl ester;glycyrrhetinic acid-cinnamon The acid/isonicotinic acid conjugate,3-fluorobenzoyl glycyrrhetinic acid benzyl ester,and the target compound were characterized by 1H-NMR,13C-NMR and HR-MS.Part III:This part carried out a series of anti-tumor pharmacological experiments on the obtained glycyrrhetinic acid derivatives,including testing the in vitro tumors using an MTT assay(human breast cancer cell)MDA-MB-231,human cervical cancer Hela inhibition assay);compound 35g-induced Hela cell apoptosis assay was tested using the Annexin V/Phosphatidylserine method.Part IV:This section summarizes and summarizes the synthetic routes and discusses some of the problems in the synthesis process.MTT assay showed that target compound 36a inhibited human breast cancer cell line MDA-MB-231 better than commercial drug gefitinib.Compounds 35g and 37b inhibited human cervical cancer cell line Hela better than commercial drug doxorubicin.Apoptosis tests indicated that compound 35g induced apoptosis in MDA-MB-231 cells.In addition,this section also explores the anti-tumor activity of the target compounds and summarizes the structure-activity relationship of the target compounds to lay a good foundation for the development of such drugs in the future.