Stereochemistry-Dependent Cytotoxicity of Some Artemisinin Derivatives

Citations Over Time

Abstract

We determined the cytotoxicity of some artemisinin derivatives against EN2 tumor cells using the MTT assay. Artemisinin (1) was clearly more cytotoxic than deoxyartemisinin (2), which lacks the endoperoxide bridge. Ether-linked dimers of dihydroartemisinin with defined stereochemistry were found to differ in the extent of cytotoxic effect on EN2 cells. The nonsymmetrical dimer (3) was more cytotoxic than the symmetrical dimer (4). The nonsymmetrical dimer of dihydrodeoxyartemisinin (5) lacking the endoperoxide bridges was also effective in the MTT assay, although less cytotoxic than 3 and 4. Similarly, the symmetrical dimer (6) was less effective than 5. Epoxides of artemisitene also showed that stereochemistry was an important factor for cytotoxicity. The results suggested that the endoperoxide bridge was not crucial for cytotoxicity to the tumor cells, but contributed to the cytotoxic effect apparently exerted by the ether linkage of the dimers. Flow cytometry data indicated that the dimers 3 and 4 caused an accumulation of the cells in the G1-phase of the cell cycle. In contrast, artemisinin (1) caused a slight increase of S-phase cells.

Related Papers

• → A review of dihydroartemisinin as another gift from traditional Chinese medicine not only for malaria control but also for schistosomiasis control(2014)48 cited
• → The development of an immunoassay for the detection of artemisinin compounds in urine.(1999)13 cited
• → Deuterated antimalarials: Synthesis of trideutero-artemisinin, dihydroartemisinin, and arteether(1996)12 cited
• → Anticancer Potential of Artemisinin Derivative-Dihydroartemisinin(2023)
• → LC–HRMS methods for the quantification of two artemisinin drugs and their metabolites in rat blood and plasma(2024)