Cytotoxic Sesquiterpenoids from Ammoides atlantica Aerial Parts

Abstract

Seven new terpenoids, namely, guaiane (1-4), eudesmane (5), and bisabolane (6) sesquiterpenoids and a furanone (7), were isolated from the aerial parts of Ammoides atlantica, a herbaceous plant growing in Algeria, together with eight known compounds. All metabolites were characterized by their 1D and 2D NMR and HRESIMS data. A combined DFT/NMR method was applied to study the relative configurations of 1-4, 6, and 7. All compounds, except 2, were assayed against MCF-7, A375, A549, HaCaT, and Jurkat cell lines. Compounds 8, 10, and 11 induced a dose-dependent reduction in cell viability with different potency on almost all cell lines used. The most active compounds, 8 and 10, were studied to assess their potential apoptotic effects and cell cycle inhibition.

Chart 1

Figure 1

UHPLC-HRESIMS profile of the chloroform extract of A. atlantica aerial parts. Peak numbers correspond to those of Chart 1. a = carboxylic acid; b = unidentified; c = isomer of 1; d = dihydroxy-dodecadienoic acid; e = hydroxy-decatrienoic acid; f = isomer of 10 and 11; g = sesquiterpene; h, j = sesquiterpene isomers; k, l = methoxylated flavonoids; j = sesquiterpene dimer.

Figure 2

Hypodiploid nuclei and cell cycle analysis of DNA content, with propidium iodide staining, were evaluated by a flow cytometric assay on A549 (panel A), Jurkat (panel B), and HaCaT (panel C) cells treated, respectively, with compound 10 or 8 (both 40–20–10–5 μM) for 24 h. Staurosporine (Sp) at 0.2 μM was used as a positive control. Results are expressed as means ± SEM of three independent experiments each performed in triplicate. Data were analyzed by the nonparametric Mann–Whitney U test. *p < 0.05, **p < 0.005, and ***p < 0.01 vs nontreated cells.