One new sesquiterpenoid, 10‐epi‐lochmolin F (1), together with 13 known sesquiterpenoids, was isolated from the roots of Croton crassifolius. The structures of these compounds were confirmed by UV, IR, MS, and NMR spectroscopic analysis. The absolute configuration of compound 1 was elucidated by analysis of X‐ray crystallography. All the 14 isolated sesquiterpenoids were screened for their inhibitory effects on ferroptosis in HT‐22 cells. Two compounds 4 and 7 showed certain inhibitory effects against RSL3‐induced ferroptosis with EC50 values of 10.8±2.3 μM and 15.5±0.5 μM, respectively. Here we firstly reported the sesquiterpenoids from C. crassifolius showing inhibitory effect on ferroptosis.
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