Molecular Determinants of Juvenile Hormone Action as Revealed by 3D QSAR Analysis in Drosophila
Figure 5
Pharmacophore models of Class I and Class II JH agonists based on CoMFA and CoMSIA result.
Models show key structural elements responsible for the hormonal activity of JH agonists. Both classes of JH compounds share regions that favor negative charge and a field that requires hydrogen bond acceptor. In both cases these elements are located at the sides of JH agonists. However, Class I compounds (A) have also additional hydrogen bond acceptor element located on the esteratic side, and a region which favors positive charges centrally. A specific feature of Class II compounds (B) is a hydrophobic region that is favored around the outside edge of a phenoxyphenol moiety. Due to the high flexibility of Class I compounds the distance between hydrogen bond acceptor atoms (e.g. esteratic and epoxy oxygens at two sides) must be between 11.5 and 13.5 Å to possess agonist biological activity in Drosophila. Highly rigid Class II compounds that show JH biological activity in Drosophila automatically fit to this requirement.