Study On The Optimization Of Synthesis Technology And Anti-Tumour Activity Of Genistein

Genistein is the main composition of the soybean isoflavone.It is deep about the study of its activity.It's reported that its acitivity is higher than the soybean isoflavone.It is similar to its chemistry structure and molecular weight with estradiol, it can compete the ER with estradiol.So it has the property of female hormone.It can lower the outbreak rate of the tumor which is related to the level of the female hormone.Women are easy to get disease after the menopause , such as the cardiovascular disease and osteoporosis.Genistein is mainly extracted from the soybean currently. But the content in the soybean is lower, so the product cost is higher. Genistein is studied generally and deeply because of its higher activity. we want to have it across the synthesis to satisfy demend of study and application.The study is divided into two steps. Firstly, we made Phloroglucinol and p-hydroxy phenyl acetic acid as the material.We got the 2,4,6,4'- tetrahydroxy deoxybenzoin after the reaction of Friedel-Craftes in the presence of catalyst.Secondly, intermediate is treated by formulation of methane and dehydrolysis followed by ring closure leading to the formation of genistein.Based on it, the research used uniform design to study the factors involved in the synthesis of genistein.With soft-ware the experiment result was used to build a proper model by stepwise regression. And then, the optimum processing condition was found. The first step: Reaction Temperature =-15℃, Reaction Time =8h, BF₃·Et₂O =2.8mol.The theoretical yield reached 67.2%, Under such processing condition, average yield reached 66.4% by verification. The second step: Reaction Temperature = 20℃, Reaction Time = 46min, BF₃·Et₂O = 6.5mmol, DMF=0.06mol, PCl₅ =2mmol.the theoretical yield reached 72.4%, average yield reached 71.6% by verification.A number of epidemiological and laboratory studies have showed that genistein is a potential cancer chemopreventing agent to sex hormone-dependentcancer, such as breast cancer and prostate cancer. But there were little reports about the effect of Gen on non-sex hormone dependent cancer, for example stomach cancer.Human gastric carcinoma cells (SGC-7901) were used as the model in vitro to investigate the effect of synthetic genistein on cell proliferation compared with the sdandard genistein and to explore the possible mechanism. Firstly, determined the genistein affect on cell growth with MTT method. Secondly, observed the appearance of morphological change under reverse discrepancy microscope, light microscope and electron microscope. Thirdly, determined cell apoptosis rate with flow cytometry.Lastly, using RT-PCR, determined the mRNA expression of Bcl-2 and Fas which are two important factors for cell apoptosis. Finding indicates that synthetic genistein has same inhibitory effect on SGC-7901 cell growth as natural genistein and may induce apoptosis by repressing the mRNA expression of Bcl-2 and promoting the mRNA expression of Fas.The study deals with chemical synthesis, technological optimization and anticarcinogenic activity of genistein. Thus the study made a good base for the study of dosage form and the new drug development.