Euphorkanlide A, a Highly Modified Ingenane Diterpenoid with a C24 Appendage from Euphorbia kansuensis

Euphorkanlide A (1), a highly modified ingenane diterpenoid with a C-24 appendage forming an additional hexahy-droisobenzofuran-fused 19-membered macrocyclic bis-lactone ring system was isolated from the roots of Euphorbia kansuensis. Its structure was determined by extensive spectroscopic analysis and quantum-chemical calculations. Compound 1 showed significant cytotoxicities against a panel of cancer cell lines (IC50s < 5 mu M). Mechanistic study revealed that 1 could induce the generation of ROS, leading to cell cycle arrest and cell apoptosis in drug-resistant cancer cell line HCT-15/5-FU.