Three-dimensional quantitative structure–activity studies of octopaminergic agonists responsible for the inhibition of sex-pheromone production in Hercoverpa armigera Original Research Article

The quantitative structure–activity relationship (QSAR) of octopaminergic agonists responsible for the inhibition of sex-pheromone production in Hercoverpa armigera, was analyzed using physicochemical parameters, molecular shape analysis (MSA), molecular field analysis (MFA), and receptor surface model (RSM), respectively. The dose-response studies were performed in vitro analyzing the effect of these compounds on intracellular cAMP production in the presence of pheromone biosynthesis activating neuropeptide (PBAN) at 1 pmol/intersegment. Six active derivatives were identified in the order of decreasing pheromonostatic activity: 2-(2,6-dimethylanilino)imidazolide () >2-(2-methyl-4-chloroanilino)oxazolidine () >clonidine () >2-(2,6-diethylanilino)thiazolidine () >2-(3,5-dichlorobenzylamino)-2-oxazoline () >tolazoline () which were all active in the nanomolar range in inhibition of cAMP production by 1 pmol PBAN/intersegment. Four other compounds were less active having Ki in the micromolar range. An MSA was tried to obtain QSAR equation that incorporates spatial molecular similarity data of those compounds. MFA on the training set of those compounds evaluated effectively the energy between a probe and a molecular model at a series of points defined by a rectangular or spherical grid. An RSM was generated using some subset of the most active structures. Three-dimensional energetics descriptors were calculated from RSM/ligand interaction and these three-dimensional descriptors were used in QSAR analysis. These results indicate that these derivatives could provide useful information in the characterization and differentiation of octopaminergic receptor types and subtypes.