Alkene lactones from Persea fulva (Lauraceae): Evaluation of their effects on tumor cell growth in vitro and molecular docking studies

Abstract

The new alkene lactone, (3E)-5,6-dihydro-5-(hydroxymethyl)-3-docdecylidenefuran-3(4H)-one (1), named majoranolide B, and three alkene lactones known as majorenolide (2), majoranolide (3) and majorynolide (4) were obtained from the aerial parts of Persea fulva (Lauraceae). The structures were elucidated in light of extensive spectroscopic analysis, including 1D, 2D NMR (1H, 13C, 1H-1H-COSY, HMBC and HSQC) and HR-ESI-MS. These compounds were screened for their in vitro antiproliferative activity in rat C6 glioma and astrocyte cells using MTT assay and in silico by molecular docking against targets that play a central role in controlling glioma cell cycle progression. Majoranolide (3) is the most active compound with IC50 6.69 µM against C6 glioma cells, followed by the compounds 1 (IC50 9.06 µM), 2 (IC50 12.04 µM) and 4 (IC50 41.90 µM). The alkene lactones 1–3 exhibited lower toxicity in non-tumor cells when compared to glioma cells. Molecular docking results showed that majoranolide establishes hydrogen bonds with all targets through its α,β-unsaturated-γ-lactone moiety, whereas the long-chain alkyl group binds by means of several hydrophobic bonds. In the present study, it can be concluded from the anti-proliferative activity of isolates against C6 glioma cells that lactone constituents from P. fulva could have a great potential for the control of C6 glioma cells.