Artemyrianolides A-S, Cytotoxic Sesquiterpenoids from Artemisia myriantha

Random screening suggested that the EtOH extract of Artemisia myriantha (Asteraceae) and its EtOAc fraction had cytotoxicity against HepG2 cells with inhibitory ratios of 30.6% and 53.5% at 50.0 μg/mL. Bioassay-guided isolation of the most active fractions (Fr. C and Fr. D) afforded 19 new sesquiterpenolides, artemyrianolides A-S (1-19), involving 13 germacranolides (1-13), four guaianolides (14-17), and two eudesmanolides (18 and 19), together with 16 known sesquiterpenoids (20-35). The new compounds were characterized by physical data analyses (HRESIMS, IR, 1D and 2D NMR, ECD), and the absolute configurations of compounds 1, 2, and 11 were determined by X-ray crystallography. Structurally, compounds 2 and 11-13 maintain an uncommon cis-fused 10/5 bicyclic system and compound 12 possesses an unusual (7S) configuration. Twenty of the compounds exhibited cytotoxicity against HepG2, Huh7, and SMMC-7721 cell lines. Compound 9 showed cytotoxic activity on both HepG2 and Huh7 cells with IC₅₀ values of 8.6 and 8.8 μM, and compounds 8 and 33 showed cytotoxicity to the three human hepatoma cell lines with IC₅₀ values of 4.9 and 7.4 μM (HepG2), 4.3 and 7.8 μM (Huh7), and 3.1 and 9.8 μM (SMMC-7721), respectively.