Studies On Synthesis And Radioprotective Effects Of Glycyrrhizin Magnesium(Gly-Mg) And N-acetyl-S-allyl-L-cysteine(NAc-SAC)

Objective:With the improvement of the nuclear application capabilities of various countries in the world,the manufacture of nuclear weapons and the construction of nuclear power plants have gradually become commonplace.At the same time,nuclear terrorisms and establishment of nuclear power plant are also threatens the safety of human life and property.Clinically,the increasing radiotherapy of cancer patients as an effective method of medical treatment is not uncommon.For those who have been engaged in radiation-related work for a long time,the effectiveness of existing radiation protection drugs is not enough.Therefore,the widespread application of nuclear energy and radiation therapy has great potential health risks while benefiting mankind.Because of these reasons,it is of great significance to develop a kind of radioprotective medicine or health food which is convenient to use,with remarkable curative effect and low toxicity.Because of glycyrrhizin and cysteine derivatives have good antioxidant and anti-inflammatory effects,based on the synthesis of glycyrrhizin magnesium(Gly-Mg)and N-acetyl-S-allyl-L-cysteine(NAc-SAC)has carried on the exploration to the radioprotective effects.Methods:This project includes the chemical synthesis and evaluation of its activitives of the target compounds Gly-Mg and NAc-SAC.The synthesis of the two compounds is based on the introduction of active groups with radioprotection based on the structure of the bulk pharmaceutical chemicals(BPC).Gly-Mg is a magnesium salt of glycyrrhizin synthesized by the substitution reaction.NAc-SAC was synthesized from L-cysteine by two-step reactions of allyl ubstitution and acylation.In the pharmacologically active part:radiation protection effects of the two compounds were evaluated by cell MTT assay,lethal dose 30-days survival rate of mice,sublethal dose mouse index test.kit antioxidation test and single cell gel electrophoresis experiment.Results:Chemical structures of two compounds were confirmed by HNMR and mass spectrometry.MTT assay showed that two compounds had no obvious toxicity to normal CHO and A31 cells and inhibited the growth of H460 and Hela cells.the survival rate in 30 days test result displayed that two compounds have better overall protective effect on irradiated mice.The seven days index experiment of irradiation mice indicated that two compounds were of certain protective effects on the hematopoietic and immune system of the exposed mice.The results of oxidative damage protection tests suggest two compounds could improve the activities of T-SOD and CAT,increase the content of GSH and reduce the content of MDA in mouse serum and tissues,but the effect was also of difference in different organs.While the results of the comet experiment show that two compounds were of significant protective effects on radiation-induced DNA damage in the bone marrow compared with the control mice.Conclusion:In summary,two compounds synthesis steps are simple and less side effects,wide range of raw materials and the bulk pharmaceutical chemicals are easy to obtain.It has little side effects on normal cells and has certain anti-tumor activity These two compounds provide good protection against DNA damage,immune and hematopoietic system damage,oxidative damage which were caused by ionized radiation.They are expected to study and develop into a radioprotective medicine or health product.