Artemselenolides I-N, sesquiterpenoid trimers from Artemisia selengensis with antihepatoma activity - structural elucidation, molecular docking and dynamics studies.

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.