Study On Synthesis And Properties Of Anti-Cancer Drugs Sulforaphane Compounds

Cancer is the second largest killer and it has shown an increasing trend every year. Among these bioactive compounds, glucosinolates (GLS) is closely linked to cancer, and only under the action of the enzyme hydrolysis of isothiocyanates (ITCs) that has the physiological activity. Sulforaphane (SFN) is one of the ITCs, it is recognized as the best compound for its anti-cancer effect. Preparation methods include chemical synthesis, enzymatic and chemical and enzymatic combined. Currently chemical synthesis methods are cumbersome and the reaction processes are hard to controled; Most reaction use toxic sulfur phosgene or carbon disulfide to introduce isothiocyanato and is difficult to achieve industrialization.The main contents of this research are:Use the three-step method to preparate SFN; Discuss the impact of the time, temperature and ratio of reactants on the yield in the manufacturing process; Use the mass spectrometry, nuclear magnetic resonance and infrared detection means to determine the product; evaluate the biological of product.The results are as follows:Use the three-step method to preparate SFN and use the column method to separate and purificate the product, then use MS, NMR and IR to character the product prepared to prove each step has synthesized target product. In preparation of 1-chloro-4-methylthio butane process, temperature 30?, reaction time 4h, sodium methanethiolate:1-bromo-4-chlorobutane=1:1 is optimal conditions. When preparate 1-isothiocyanato-4-methylthio butane, we first generated 1-thiocyanato-4-methylthio butane, and then refluxed it in DMF, 1-thiocyano-4-methylthio butane is isomerized to 1-isothiocyanato-4-methylt-hio butane. Conversion of the preparation of 1-thiocyanato-4-methylthio butane conversion was influenced by reaction time, temperature, and the amounts of reactants. Temperature 80?, reaction time 3h,1-chloro-4-methyl-thio butane:sodium thiocyanate=1:1.2 is the best conditions. In preparation of SFN, temperature 0?, reaction time 30 min, sodium methanethiolate: 1-bromo-4-chlorobutane=1:1.1 is optimal conditions.We used cck-8 to detecte the impact of different products on the activity of cancer cells, the subjects is A549 human lung cancer cells. Study found that the activity of SFN is slightly high then 1-isothiocyanato-4-methyl-thio butane. 1-thiocyanato-4-methylthio butane has no anti-cancer effect. This rssult shows-N=C=S is the main site of anti-cancer activity, and the side chain of product is anti-cancer secondary sites. We observed the tumor cells state before and after administration by inverted microscope found that isothiocyanates can not only inhibit the growth of tumor cells, but also can to change the morphological characteristics of tumor cells.