Synthetic Study Of 32 Chinese Herbal Medicines Concocted Chromatography And Dna Methyltransferase Inhibitors

This dissertation has two parts. The first part is the study of chemical changes of Traditional Chinese Medicine (TCM) during the preparing process, in order to reveal the substantial base and mechanism of increasing effectiveness and detoxication. The second part is the synthesis of the novel small-molecule inhibitors of DNA methylatransferase.The preparing process of TCM is one of preparing techniques according to pharmic characters and clinical requirements. The chemical constituents of TCM are remarkably changed during the preparing process, due to the effect of heating, steeping and so on. The changes of the constituents consequentially result in the changes of the characters of TCM. It indicates that the changes of the constituents is the substantial base. Twelve kinds of TCM have been chosen as subjects, applying HPLC to analyse the whole chemical changes. For a certainty, there are chemical changes in the prepared drugs through comparing the chromatograms of raw and prepared drugs. The results let us have a good chance to reveal the substantial base of preparing process and show the scientific proof of the preparing process and improve the process to accelerate the development of the preparing process of TCM.As the developing of epigenetics, it has been deeply realized that DNA methylation plays an important role in regulating genes expression. The possibility to reactive epigentically silenced genes has generated considerable interest in the development of DNA methyltransferase inhibitors. The most widely known methylation inhibitors are cytidine analogues. However, due to their substantial cytotoxicity, they are limited in their application. Therefore, it is urgent to identify chemical compounds with an ability to directly block human DNA methyltransferases. It has been reported that a small-molecule, novel, mechanism-independent compound has high activity in inhibiting the DNA methyltransferase. Based on the possibility for chemical modifications, a series of derivatives were synthesized by a very simple way with high yield, which all represent promising candidates for cancer drug development.