Design,Synthesis And Antitumor Activity Of 2-methoxyestradiol Derivatives

Nowadays,cancer is an illness that causes a serious of threats to human health.The treatment of cancer has become an important task which we need to address.In the three therapies of tumor,surgery and radiotherapy are local treatments,which are generally applicable patients with early cancer.However,chemotherapy as a means of cancer treatments,could play a positive therapeutic effect on malignant.Though,these chemotherapy drugs can effectively reduce the recurrence rate of cancer,they also have some shortages,such as the lack of selectivity to cancer cells and the high toxicity.2-Methoxyestradiol(2ME2)is an endogenous metabolite of estrogen which has antitumor effects.It has attracted much attention because of its wide range of biological activities.Pyrimidines and nucleosides analogues are very important compounds due to their biological and pharmacological activities,such as antitumor and antivirus.The brominated alkanes are as the’bridges’,linking the 2ME2 and pyrimidines and nucleosides.Therefore,we synthesized some new derivatives,in order to get some new compound which possessing high-efficiency to tumor cells,low-toxicity to normal organs,and promising pharmaceutical development.The main research work of this study is outlined as follows:1.IntroductionThe paper briefly describes the influence of malignant tumors in the world today and concludes several effective ways of treating malignant tumor and several kinds of antitumor drugs;also review focuses on the mechanism research of 2ME2.2.The research background and synthetic route of target compounds.There are two major parts in this content.One of this is the design and synthesis of 3-and 17-2-methoxyestradiol pyrimidines’ derivatives.And the other is the design and synthesis of 3-and 17-2-methoxyestradiol nucleosides,derivatives.3.Sythesize experimentsDescribe the synthetic routes of target compounds,and the structures of the compounds have been characterized by HRMS,1H NMR and 13C NMR.4.The antitumor activity evaluation on vitroThe vitro toxicities of the target compounds were tested on tumor cell lines involved BEL-7404,MCF-7,MDA-MB-231,T-24 and so on,through MTT method.Some of the inhibition ratios were more than 50%at a concentration of 20 μM,we tested their IC50,and some compounds were chosen to study the mechanism of antitumor.