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

AbstractIn 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.