Quantitative structure-activity relationship of insect juvenile hormone mimetic compounds

Juvenile hormone mimetic activities on Aedes aegypti (yellow-fever mosquito) and Tenebrio molitor (yellow mealworm) of compounds having (2E,4E)-3,7,11-trimethyl-2,4-dodecadienone structures were comparatively and quantitatively analyzed in terms of their physiochemical structural parameters and by regression analysis. They were structurally composed of three classes, ester and thiol ester derivatives, amides, and ketones, depending on the C1 substituents. The results indicated that the steric dimensions and the hydrophobicity of the whole molecule are important factors in governing the activity through these classes as well as through both insect species. The effects of the structure of the C1 and C11 substituents, the two ends of the chain molecule, are specific to the insect. The length along the bond axis of the C1 substituents is significant and the hydroxy and alkoxy functions attached to the C11 atom favor the activity on A. aegypti, whereas with T. molitor the width of the C1 substituents in the direction perpendicular to the bond axis is significant and the position-specific hydrophobicity of the C1 moiety enhances the activity. The activity is also affected differently by the compound types. The amide and ketone series of compounds are more active than the corresponding ester type of compounds on T. molitor, while the favorable types on A. aegypti are the ester and ketone derivatives. Correlation equations formulated for 85 active compounds on A. aegypti and 84 compounds on T. molitor led us to draw a hypothetical "mode of action" model for each species, which visualizes the overall similarity as well as the species differences of the interaction site or the receptor and may show the structural conditions necessary for activity.