Design, Synthesis And Anti-tumor Activity Of Tetrandrine And B Derivatives

Malignant tumor is one of the most serious diseases to human and drug therapy is one of the most important methods to cure this disease.Natural products with anticancer activity are the main source for the research and development of new anticancer medicines.Tetrandrine and fangchinoline are the main alkaloids of Stephania tetrandra which contains many other alkaloids.Based on our investigation of literature and preliminary study,we found both tetrandrine and fangchinoline displayed good inhibitory activity on tumor cells.In addition,fangchinoline could induce autophagic cell death of liver cancer cells,which indicated a novel mechanism of anti-tumor action.In this research,our main efforts and purposes were to design and synthesis a series of novel benzyl isoquinoline-type alkaloids which possessing a novel mechanisms of anticancer activity.As a result,40 derivatives of bibenzylisoquinoline alkaloids were design and synthesized from tetrandrine as well as fangchinoline which had been prepared as staring material from Stephania tetrandra by our research group.Their anticancer activity,structure-activity relationship(SAR)and mechanisms of action were also studied.Some of these compounds showed potent inhibitory activities against tumor cell lines PLC/PRF/5 and MHCC97 L.Besiddes,the author has finished the synthesis process of the two candidate drugs of tetrandrine and fangchinoline.These results will facilitate the discovery of novel,high performance and low cost antitumor drugs with novel mechanisms of action from natural products.