QSAR AND LIGAND-BASED PHARMACOPHORE MODELS OF DIBENZOYLHYDRAZINES WITH INSECTICIDE ACTIVITY AGAINST THE SILKWORM BOMBYX MORI L

Dibenzoylhydrazines are employed as growth regulators that act through the induction of a lethal larval molting process in insects. In this study quantitative structureactivity relationship (QSAR) and pharmachophore models of ecdysone agonistic activity of dibenzoylhydrazine insecticides, measured in the silkworm Bombyx Mori lepidopteran species cell lines, are presented. Molecular mechanics calculations using the MMFF94s force field were employed to model the dibenzoylhydrazine structures. The experimental insecticidal activity (pEC(50) values) was correlated to the calculated variables using the multiple linear regression (MLR) approach. The most stable and predictive MLR model had the following statistical parameters: r(training)(2) = 0.870, r(test)(2) = 0.731, q(LOO)(2)= 0.808, RMSEtr = 0.406, RMSEext = 0.385. Pharmacophore hypotheses were generated for the same series of compounds and validated using the partial least squares (PLS) approach. Two hydrogen bond acceptors, one hydrogen bond donor, one hydrophobic group and one aromatic ring features were found to be important for the insecticidal activity.