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, (3 E )-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 ( 1 H, 13 C, 1 H- 1 H-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 IC 50 6.69 µM against C6 glioma cells, followed by the compounds 1 (IC 50 9.06 µM), 2 (IC 50 12.04 µM) and 4 (IC 50 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.