Design, Synthesis, and Antitumor Activities of Isomers of Artemisinin Dimer Derivatives

In recent years, numerous studies have reported on the anti-tumor properties of artemisinin and its derivatives. However, the relationship between their artemisinin chirality and activity remains unknown. In this study, we synthesized a series of artemisinin dimer derivatives with three different chiral structures and tested their antiproliferative activity in MCF-7 and HepG2 cells using the CCK-8 assay. Interestingly, we discovered that artemisinin dimer derivatives with β, β and α, β conformations at C-10 exhibited stronger anti-tumor activity than those with an α, α configuration in MCF-7 and HepG2 cells. Notably, compound 4 showed an activity of 0.06 μM in MCF-7 cells. This study demonstrates the relationship between the conformation and activity of artemisinin dimer derivatives, and these derivatives have the potential to be developed into anti-cancer drugs.