Studies On The Synthesis And Anti-tumor Activities Of Novel Organosilicon Phosphoramidates And Schiff Base Of Amino Acid Conjugates Containing Tegafur

5-Fluoro uracil (5-FU) is a kind of antimetabolic drug which can prevent the formation of pyrimidine nucleotides in cancer cell. It is used for treating the rectum cancer, colon cancer and stomach cancer, etc. Its derivative, N'-2-tetrahydrogenfuranyl-5-fluoro uracil (Tegafur) , is also a kind of drug for the clinical cancer-therapy. Because they have some inhibition effects on bone marrow, intestine and stomach side reaction and the greatly poisonous side effects as well, their clinical application is restricted. So, for a long time, people carried out various modifications on 5-FU and tegafur, attempting to develope conjugates of 5-fluoro uracil wi'th great curative efficiencies, high selectivities and low poisonous side effects as guide compounds of anti-cancer drugs.Silatranes are new-type organosilicon compounds with specific molecular structure and diverse biological activities. Through a large amount of domestic and international researches, it is indicated that silatranes containing aminoalkyl groups exhibit strong anti-tumor activities. Because of their totally different action mode from common medicine, especially when used with other general chemical medicines at the same time, they can give coordinated effects, which make the medicine efficiency more lasting and stronger. So this kind of compound is considered to possess very promising prospect as the new-type medicine. According to the combinability principle of bioactivity, We combined tegafur and silatranes with alkyl (phenyl) dichlorophosphates to synthesize new-type phosphoramidates Ia~ Ie which had never beenreported.In recent years, as a very important branch of synthetic chemical drugs, researches on Schiff base compounds and their metal complexes were becoming active. Some kinds of Schiff base compounds exhibit strong anti-tumor or bactericidal activities, when coordinated with metal ions, their bioactivities become stronger than before. Among them, research on the Schiff base compounds of amino acid attracts great attentions of scientists, due to its special significance. We coupled tegafur with Schiff base compounds of glycin or alanine to afford Schiff base derivatives of amino acid containing tegafur IIa~IIm , on the purpose of decreasing the toxicity of tegafur and making the medicine efficiency more lasting and stronger under coordinated action.Structures of target compounds mentioned above were characterized by elemental analysis, IR, 1HNMR, 31PNMR and MS spectroscopy. In the same time, the physical and chemical properties were also discussed and analysed systematically together with the spectrum properties.The preliminary test of anti-tumor activity was carried out in light of the MTT method in vitro. The result indicated that, under the concentration of 5ug/ml, Comp I d exhibit inhibition activity to the colon cancer and liver cancer of human being, while Comp I c only possess inhibition activity to the colon cancer.