Abstract
Isomeric eudesmane-type sesquiterpene lactones: alantolactone (1), isoalantolactone (2) and diplophyllin (3), the main constituents of Inula helenium L. root essential oil, are strong antistaphylococcal agents. Energetically favorable conformations of these were calculated (MM+ and MMFF94 molecular mechanics and AM1 and PM3 semi-empirical methods) and mutually compared. The compounds were additionally described in terms of selected 2D and 3D molecular descriptors. Alantolactone and isoalantolactone mainly adopt “U”-shaped conformations (>99%, calculated at 298 K; “closed” geometries), with the carbonyl moiety being rather sterically hindered by the axial methyl group. In contrast, the cyclohexene and lactone rings of diplophyllin are mutually oriented in such a way to give the overall “S”-shape to the molecule (“open” geometry). These conformational differences, inherently influencing the optimal interaction of lactones 1-3 with the binding region of target biomolecules, could be, at least partially, responsible for the higher observed antistaphylococcal activity of diplophyllin in comparison with the other two isomeric lactones.