Design,Synthesis And Preliminary Activity Evaluation Of Novel THA Topo ? Inhibitors & Expression And Activity Assay Of DIS/DIIS Candidate Proteins

Topoisomerase I(Topo I)inhibitors have good anticancer activity and have been used as anticancer drugs.However,these drugs have fast metabolism and strong side effects,so it is very important to find more efficient and less toxic drugs.Tetrahydroangustine(THA)is a plant-derived alkaloid that has been shown to have anti-tumor activity.The first part of the thesis simulates the biosynthetic pathway of THA,obtain its precursor from STR1 and finally got a series R and S configurations of the compounds with THA sskeleton.Preliminary activity evaluations confirmed that these compounds are novel Topo I inhibitors and can kill HepG 2 tumor cells.The plant-derived Pictet-Spenglerases are gating enzyme for the synthesis of thousands of alkaloids in nature,and its catalytic product are important precursors for many drugs.So far,four plant-derived Pictet-Spenglerases have been discovered,two of which are deacetylipecoside synthetase(DIS)and deacetylisoipecoside synthetase(DIIS).Up to now,the study of DIS/DIIS is still in its infancy,and the DNA sequences of these two enzymes have not been clarified yet.In the second part of this thesis,seven DIS/DIIS candidate sequences that were obtained from transcriptome analysis were successfully expressed using Rosetta,GS115 and M15 expression systems.Unfortunately,the activity of these proteins has not been detected so far.Therefore,the study of DIS/DIIS will be continued in different perspectives.