Euphorusenes A and B: Triterpenoids Featuring a 7/5/6/6/5 Ring System from Euphorbia humifusa

Abstract Two unprecedented triterpenoids, euphorusenes A (1) and B (2), together with fern-8-en-3β-ol (3), were isolated from Euphorbia humifusa. Compound 1 represented the first example of a triterpenoid possessing a 7/5/6/6/5 skeleton with migrated methyl-25, whereas 2 featured a distinct 7/5/6/6/5 cyclized scaffold characterized by methyl-25 migration, loss of C-4, C-23, and C-24, and a seven-membered lactone A ring. The structures of 1 and 2 were elucidated by spectroscopic methods and X-ray crystallographic analyses. Compound 1 displayed cytotoxicity against HCT-116 cells with an IC50 value of 8.0 ± 0.8 μM. Further biological evaluation revealed that 1 may trigger ferroptosis in HCT-116 cells by inhibiting GPX4.