Identification of Novel Artemisinin Hybrids Induce Apoptosis and Ferroptosis in MCF-7 Cells

A series of novel 1,3,4-oxadiazole-artemisinin hybrids have been designed and synthesized. An MTT assay revealed that most of tested hybrids showed more enhanced anti-proliferative activities than artemisinin, among which A8 had the superior potency with IC50 values ranging from 4.07 mu M to 9.71 mu M against five tested cancer cell lines. Cell colony formation assays showed that A8 could inhibit significantly more cell proliferation than artemisinin and 5-fluorouracil. Further mechanism studies reveal that A8 induces apoptosis and ferroptosis in MCF-7 cells in a dose-dependent manner, and CYPs inhibition assays reveal that A8 has a moderate inhibitory effect on CYP1A2 and CYP3A4 in the human body at 10 mu M. The present work indicates that hybrid A8 may merit further investigation as a potential therapeutic agent.

Automated summary

A series of novel 1,3,4-oxadiazole-artemisinin hybrids have been designed and synthesized, among which A8 showed superior anti-proliferative activities against cancer cells. Further mechanism studies revealed that A8 induces apoptosis and ferroptosis in cells, and exhibits moderate inhibitory effects on CYP enzymes in the human body.