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

Abstract

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 Artemisia argyi 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 (1), one new disesquiterpenoid (2), three new guaianolides (3–5), 12 known sesquiterpenoids (6–17), and 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 their experimental and calculated ECD spectra. The absolute configuration for 2 was determined by X-ray diffraction analysis. Guaianolide 8 was the most potent sesquiterpene lactone, inhibiting the PI3K/AKT pathway with an IC50 value of 8.9 ± 0.9 μM.

Hot off the Press

“…The meroterpenoid artejasminolide 3 , from Artemisia argyi , is the first example of an adduct between a sesquiterpene lactone and a methyl jasmonate. 3 The structure of the rearranged abietane diterpenoid rugosiformisin A 4 , from Isodon rugosiformis , was established by X-ray analysis. 4 The authors propose a biosynthetic pathway to rugosiformisin A 4 involving a semipinacol rearrangement and a bioinspired synthesis of rugosiformisin A 4 has been completed.…”

Recent advances in the syntheses of guaianolides

“…Many new molecules have also been isolated lately within this class. 12 This section describes various strategies used for the synthesis of 6,12-guaianolides, involving diastereoselective allylation, photocyclization or rearrangement or ring enlargement, diastereoselective aldol reaction, diastereoselective ketone alkylation and enediyne and dienyne metathesis, which are briefly depicted in Fig. 3.…”