Discovery of N-phenyl-isoindole-1,3-dione derivatives as potent insect chitinase OfChi-h inhibitors through virtual screening

Ostrinia furnacalis represents a destructive lepidopteran pest causing up to 30% yield losses in maize crops globally. Its larvae penetrate plant tissues, disrupt nutrient transport, and transmit viral and microbial pathogens, exacerbating food security concerns. Current management approaches for O. furnacalis primarily rely on synthetic pesticides. Targeting chitin metabolism presents a promising strategy for green insecticide development. Specifically, OfChi-h, an essential chitinase for O. furnacalis molting and survival, has emerged as a viable target. This study identified a N-phenyl-isoindole-1,3-dione (PI) scaffold as a novel class of OfChi-h inhibitor through virtual screening strategy. Notably, compound PI-17 demonstrated potent inhibitory activity against OfChi-h with a K_i value of 2.3 μmol L^–1. PI-17 exhibited significant insecticidal activity against lepidopteran pests O. furnacalis, comparable to the control drug hexaflumuron. Scanning electron microscopy (SEM) analysis revealed morphological alterations in the cuticles of O. furnacalis larvae treated with PI-series compounds. Electrostatic potential (ESP) and density functional theory (DFT) calculations explored the variations in biological activities of the PI-series compounds at atomic and electronic levels. Additionally, comprehensive safety evaluations assessed the impact on the natural enemy Trichogramma ostriniae and nontarget organisms. These findings introduce a novel class of lead compounds, PI derivatives, showing significant potential for developing eco-friendly insect growth regulators to control O. furnacalis.