A Dimerosesquiterpene and Sesquiterpene Lactones from Inhibiting Oncogenic PI3K/AKT Signaling in Melanoma Cells.

A library of more than 2500 plant extracts was screened for activity on oncogenic signaling in melanoma cells. The ethyl acetate extract from the aerial parts of displayed pronounced inhibition of the PI3K/AKT pathway. Active compounds were tracked with the aid of HPLC-based activity profiling, and altogether 21 active compounds were isolated, including one novel dimerosequiterpenoid (), one new disesquiterpenoid (), three new guaianolides (-), 12 known sesquiterpenoids (-), and four known flavonoids (-). A new eudesmanolide derivative () was isolated as an artifact formed by methanolysis. Compound is the first adduct comprising a sesquiterpene lactone and a methyl jasmonate moiety. The absolute configurations of compounds and - were established by comparison of their experimental and calculated ECD spectra. The absolute configuration for was determined by X-ray diffraction analysis. Guaianolide was the most potent sesquiterpene lactone, inhibiting the PI3K/AKT pathway with an IC value of 8.9 ± 0.9 μM.