Artemselenolides I-N, sesquiterpenoid trimers from Artemisia selengensis with antihepatoma activity - structural...

Artemselenolides I-N (1-6), six undescribed guaiane-type sesquiterpenoid trimers (GSTs), as well as 24 known compounds (7-30), were isolated from Artemisia selengensis. Their structures and absolute configurations were elucidated through comprehensive spectral analyses, theoretical ECD calculations, NMR computations, and single-crystal X-ray diffraction. Structurally, compound 1 represented the first example of GST featuring a 1″,10″-seco-guaiane sesquiterpenoid unit; compounds 1-6 were biogenetically formed through two [4 + 2] cycloadditions. Specifically, compounds 1-5 featured linkages at C-1-C-13', C-4-C-11', C-1'-C-13″, and C-4'-C-11″, whereas compound 6 exhibited bonds at C-2-C-13', C-4-C-11', C-1'-C-13″, and C-4'-C-11''. Antihepatoma assay indicated that compounds 1-6 exhibited inhibitory activity on HepG2, Huh7 and SK-Hep-1 cells with IC₅₀ values ranging from 6.2 to 14.8, 5.0 to 14.2, and 5.4 to 16.1 μM, respectively, which were comparable to those of sorafenib. It was predicted that the most active compound 2 targets on vascular endothelial growth factor A (VEGFA) by integrating network pharmacology and molecular docking (score: 5.5) analyses, while molecular dynamics simulations confirmed stable binding interactions.