Design,Synthesis And Antitumor Activity Of Pentacyclic Triterpenes Conjugated-5-Fluorouracil Or Hydrogen Sulfide Donors

Cancer is a disease which serious threat to people’s lives and health.Modification through introducing active pharmacophore to natural products,and evaluation the pharmacological activity in corresponding filed,has become a research hot in drug development.Oleanolic acid,glycyrrhetinic acid and ursolic acid are representative compounds of pentacyclic triterpenes,which are the active ingredients of herbal medicine.They have been widely researched as their biodiversity activities.Fluorouracil,a market antitumor drug,because of its poor selectivity leading to toxic side effects,just belongs to the second category antitumor drugs in clinical application.Though the research on hydrogen sulfide gas signal molecule mainly in the nervous and cardiovascular system,the latest research exhibites that hydrogen sulfide donor could improve the antitumor activity of carriers.Thus,in this study,fluorouracil and hydrogen sulfide donors were attached to pentacyclic triterpenes oleanolic acid,glycyrrhetinic acid and ursolic acid to afford series derivatives of pentacyclic triterpenes-fluorouracil or H2S donors.The purpose of this study is to get some new compounds which possessing high-efficiency to tumor cells and low-toxicity to normal organs;and develop a new route for antitumor drug research.The main research work of this study is outlined as follows:1.IntroductionThe current classification of new anticancer drugs,the progress in the research of pentacyclic triterpenes oleanolic acid,glycyrrhetinic acid and ursolic acid are described.As well as the background and research content of this study are also summarized.2.The synthetic routes of target compounds.There are two parts in this section.One is the design and synthesis of the pentacyclic triterpenes-fluorouricil derivatives.And the other one is the design and synthesis of pentacyclic triterpenes-H2S donor derivatives.3.Chemical experimentsThe synthetic route of each compound was described detailly.And the structure of each target compound was characterized by HRMS,1H NMR and 13C NMR.4.The antitumor activity evaluation in vitroThe antitumor activity in vitro of each target compound was tested by MTT method on tumor cell lines A549,BEL-7404,MCF-7,K562 and Bel-7402.According to their IC50 values,structure activity relationship was studied and some compounds were chosen to study the mechanism of action in future research.