20-hydroxyecdysone receptor ligand binding domain: 1. A semiempirical study of dibenzoylhydrazines selectivity

Abstract

Dibenzoylhydrazine (DBH) pesticides, such as RH5849 and RH2485, are non-steroidal agonists of the insect hormone 20-hydroxyecdysone (20E) that exert their insecticidal effect by interaction with the 20E receptor (EcR). Differently from RH5849, RH2485 is selectively toxic to lepidopteran species. In this work, we evaluate by the semiempirical methodology the structures and energetics of the complexes between RH5849 and RH2485 and models of Lepidoptera and Diptera EcRs. Models were constructed by homology modeling of the EcR binding region of the lepidopteran Manduca sexta and of the dipteran Drosophila melanogaster. A preliminary study of the interaction between the models and the natural agonist was implemented. The calculated enthalpy associated with the binding forces between synthetic agonists and simplified receptor models presented qualitative agreement with the biological profile of the DBHs towards Lepidoptera and Diptera. A rationale for the observed differences in the pesticide activities of RH5849 and RH2485 based on the structures of the modeled complexes is presented.