Artemselenoids A−H, eight guaiane-type sesquiterpenoid dimers from Artemisia selengensis and their antihepatoma activities

Abstract

Eight undescribed guaiane-type sesquiterpenoid dimers (GSDs), artemselenoids A−H (1−8), together with nine known GSDs (9−17), were isolated from Artemisia selengensis. Their structures and absolute configurations were determined through comprehensive spectral analyses, theoretical ECD calculations, and NMR computations. Chemically, compound 1 represented the first example of two guaianolide lactone units dimerizing through unprecedented C-3−C-11′ and C-4−C-13′ bonds via a [2 + 2] cycloaddition reaction and producing a structurally unique 5,4 spirocyclic system; compounds 2−8 were biogenetically formed through a [4 + 2] cycloaddition reaction. Specifically, compounds 2−7 were connected by C-1−C-13′ and C-4−C-11′ bonds, compound 8 was linked by C-1−C-13′ and C-4−C-11′ bonds. Antihepatoma assay indicated that the most active compounds 3 and 8 demonstrated significant inhibitory effects on three hepatoma cell lines, with IC50 values of 7.4 and 5.1 μΜ (HepG2), 5.9 and 8.6 μΜ (Huh7), and 20.9 and 9.6 μΜ (SK-Hep-1), which were equal to those of positive control sorafenib.