en |
Isolation and Elucidation of 15-Acetylguanacone from Soursop ( Annona muricata Linn) Fruit and Molecular Docking Experiments
AGU, KINGSLEY CHUKWUNONSO; OKOLIE, NGOZI PAULINUS; FALODUN, ABIODUN; ERHARUYI, OSAYEMWENRE; IGBE, IGHODARO; ELEKOFEHINTI, OLUSOLA OLALEKAN; EDOSA, RICHARD OSARO & OGHAGBON, STEPHEN EWEMADE
Abstract
Annona muricata (Soursop) has attracted attention due to its content of
annonaceous acetogenins, a large family of naturally occurring polyketides isolated from
various species of the genus Annonaceae. The ethyl acetate fraction of Annona muricata was
subjected to standard isolation protocol-gradient and isocratic silica gel column
chromatography- to obtain three waxy and whitish amorphous compounds, 002/A1, 002/A2 and
002/C. The structure of compound 200/A2 was elucidated using 1H-NMR spectroscopy, infrared
spectroscopy and electron impact (EI+) mass spectroscopy. The molecular weight of 200/A2
was determined as 662 by EI-MS ([M+H]+ : m/z = 662.1) leading to the molecular formula
C39H66O8 as obtained using high resolution MS. The existence of an α, β-unsaturated γ-lactone
moiety, non-hydroxylated at the C-4 position, was suggested by an IR carbonyl absorption at
1735.9 cm-1 and 1662.7 cm-1; the IR also gave signal for hydroxyl group at 3339.0 cm-1. The
presence of a characteristic vinyl proton δ 7.24 (H-35, d), which is characteristic for α, β-unsaturated γ-lactone was confirmed by the 1H-NMR spectrum. The compound was thus
elucidated to be 15-acetyl guanacone, an acetogenin. This acetogenin has not been reported in
Annona muricata previously. The compound was subsequently subjected to molecular docking
experiments which revealed that it targets and binds to vascular endothelial growth factor 2,
VEGF2 (-8.5kcal/mole) and α1 β2 integrin (-6.8kcal/mole), This thus suggests that 15-acetyl
guanacone prevents metastasis and invasion by cancer cells, and ultimately initiates apoptosis.
Keywords
VEGF2; Integrin; Cancer; Acetogenins; Apoptosis; Soursop
|