The New Synthesis And Antitumor Activity Of Matrine Derivatives Research

Cancer is one of the major malignant diseases detrimental to health,studies onantitumour drugs has become a rapidly growing field of medical science today.Plantsources of anticancer drugs have diversity chemical structure and therapeutic mechanism,therefore, it is a potential for tumor treatment research to look for a variety of targets of anti-tumor substances from plant sources. Matrine and oxymatrine are an alkaloid extractedfrom the legume genus plant sophora flavescens or flat plant sophora, the matrinecompounds as a chinese traditional medicine, with its low toxicity and efficient advantageswill become a promising anti-cancer drugs. The natural flavescens alkaloids markedlyinhibited cell growth and induced apoptosis. However, clinical application of flavescensalkaloids is severely limited by their low bioavailability,poor activity and large amount ofdosage. To find highly reactive antineoplastic drugs, structural modification of flavescensalkaloids is an important research direction of alkaloids.In order to reduce toxicity, enhancethe pharmacological activity of matrine, a series of matrine derivatives were synthesized byusing natural extract of sophora flavescens alkaloids.This research lay a foundation for further research on synthesis of new flavescensalkaloids derivatives and activity screening. The main results and conclusions of this thesisare listed as follows:1. Based on the correlative materials from documents, the synthesis and pharmacologyof matrine and its derivates had been briefly summarized,the structure-activity relationshipof some matrine derivates was included,advances in research of matrine and its derivateswere reviewed.2. The paper focused on matrine as a lead compound with aromatic aldehydes andpyridine aldehydes using Claisen-Schimidt condensation reaction, ten matrine derivativeswere designed and synthesized under the catalysis of sodium hydride,and theirreactionconditions were optimized in this paper. At the same time hydrogenation andhydrolysis to give deoxy-matrine and matrine acid were also carried out. The structures of these compounds have been determined by¹HNMR, LC-MS, IR spectra and elementalanalysis.3.Oxymatrinium tetrachloridoferrate（III） and oxymatrinium-1-ium trichlorozincatecompounds were synthesized by reaction with natural activity of the ligand oxymatrine andmetal salt compounds. The Oxymatrinium tetrachloridoferrate（III） compounds wasdetected by X-ray diffraction analysis. Result showed that Fe（III） in the forms of[FeCl₄]^-with O（2） protonated cationic matrine to produce an ionic metal compounds.Crystal library to check this result there are no records for the first time reported.4. The anticancer activity in vitro against PC-3cells cell line had been evaluated byMTT assay respectively, the bioactive assay showed that most new compounds exhibited asignificant antitumor activity, especially the matrine pyridine （C1,C2,C3） andfluoro-substituted （B1）aromatic ring derivatives are increased over3to4times thanmatrine, it is worth further study.