Dimerosesquiterpene and sesquiterpene lactones from Artemisia argyi inhibiting oncogenic PI3K/AKT signaling in melanoma cells

A library of more than 2’500 plant extracts were screened for their activity on oncogenic signaling in melanoma cells. The ethyl acetate extract from aerial parts of Artemisia argyi displayed pronounced inhibition of the PI3K/AKT pathway. Active compounds were tracked with the aid of HPLC-based activity profiling, and a total of 21 active compounds were isolated, including one novel dimerosequiterpenoid (1), one new disesquiterpenoid (2), three new guaianolides (3-5), 12 known sesquiterpenoids (6-17), as well as four known flavonoids (19-22). A new eudesmanolide derivative (13b) was isolated as an artifact formed by methanolysis. Compound 1 is the first adduct comprising a sesquiterpene lactone and a methyl jasmonate moiety. The absolute configurations of compounds 1 and 3-18 were established by comparison of experimental and calculated ECD spectra. The absolute configuration for 2 was determined by X-ray diffraction. Guaianolide 8 was the most potent sesquiterpene lactone, inhibiting the PI3K/AKT pathway with an IC50 of 8.9 ± 0.9 μM