Conformation of oleuropein, the major bioactive compound of Olea europea

Oleuropein is the major bioactive component of Olea europea (the olive tree) and possesses strong antioxidant as well as anti-inflammatory, antiatherogenic and anticancer properties whereas it has been shown to bind to endogenous peptides. Thus the understanding of its conformation is important and could shed some light into its mechanism of action. The aim of the current study was to investigate the lowest energy conformation of the molecule. Thus a conformational search using molecular mechanics has been conducted, the resulting data were grouped by cluster analysis and the lowest energy conformers have been identified. Oleuropein adopts a closed conformation where its phenolic hydrogens form a hydrogen bond network with the hydroxyl groups of the glucose moiety. The lowest energy conformer structure found has been further refined using semi-empirical and ab initio calculations. Molecular dynamics were also performed in order to confirm the geometry of the lowest energy conformation found and and AIM calculations in order to verify the “tight” conformation adopted by the molecule.