Rational Design of azo-aminopyrimidine Derivatives as the Potent Lepidoptera-Exclusive Chitinase Inhibitors

s : As the number one pest responsible for the loss of important crop corn, control of Ostrinia furnacalis is critical. The chitinase Of Chi-h, isolated from the agricultural pest Ostrinia furnacalis , has been recognized as a potential insecticide target due to its species-specificity only in lepidoptera pests and not found in mammals and plants. In this study, a series of azo-aminopyrimidine analogues were synthesized as Of Chi-h inhibitors by rational molecular optimization. Among them, compounds 9b , 10a , and 10g showed K i values of 23.2, 19.4 and 43.2 nM against Of Chi-h, respectively. Molecular docking studies were carried out to explore the molecular basis for the high potency of these compounds against Of Chi-h. In addition, the morphological changes of the inhibitor-treated Ostrinia furnacalis larvae cuticle using scanning electron microscopy were conduct. Furthermore, leaf dipping and pot experiments of target compounds were assayed, compounds 10a showed better insecticidal activity against the Plutella xylostella and Ostrinia furnacalis than diflubenzuron and chlorbenzuron. At the same time, the toxicity of these compounds to natural enemies Trichogramma ostriniae and rats was negligible. The present study demonstrates that the azo-aminopyrimidine skeleton can be used as a novel, low-cost scaffold for insect chitinolytic enzyme inhibitors, with the potential to become a new green insecticide.