Synthesis And Biological Activity Evaluation Of Novel Artemisinin Dimers

Object: Cancer has been one of the leading causes of human death and seriously threats human life.Artemisinin,a drug was isolated from the herb plant Artemisia annua L.,is a sesquiterpene lactone containing a 1,2,4-trioxane moiety,which has been proved as an effective treatment of malaria.According to the previous researches,artemisinin and its derivatives had desirable anti-proliferation activity to various kinds of cancer cell lines,but less cytotoxicity to normal cells.Hence,the artemisinin-related compounds become an attractive candidate for developing novel cancer chemotherapy.In this study,a series of novel artemisinin dimers were synthesized and their anti-proliferation activities were evaluated.Method: A novel artemisinin dimer 17 was synthesized and the absolute configuration of 17 was determined by X-ray single crystal diffraction.In order to study the structure-activity relationship of artemisinin dimer 17,twenty-five derivatives were synthesized.The in vitro anti-proliferation activity and cytotoxicity of these derivatives were assessed.Results: The artemisinin dimer 17 has shown significant inhibitory activity against various tumor cells.However,it also has a high cytotoxicity against Vero cell,which restrict the possibility for in vivo study of its anti-cancer activity.It was found that the water solubility derivatives of 17 could reduce the cytotoxicity,thus have a better theroputical window.The derivatives 24,32,37 and 42 could be the prodrugs of compound 17 worth for further studies.Conclusion: Compounds 24,32,37 and 42 as the prodrug of 17 are worth for further study.