Triazinobenzoxazepine Derivatives Identified as Dual-Chitinase Inhibitors to Regulate Insect Growth.

The insect chitin metabolism system is an ideal target for species-selective pesticide development, in which OfChi-h and OfChtI jointly mediate chitin degradation. However, existing Chitinase inhibitors face limitations in efficacy and specificity, necessitating innovative computer-aided driven lead discovery strategies. Herein, a dual-target virtual screening was performed to discover triazinobenzoxazepine derivatives (TBZs) as novel Chitinase inhibitors. Compound TBZ-15 emerged as a potent dual inhibitor with Ki values of 0.64 μM and 0.43 μM against OfChi-h and OfChtI, respectively. TBZ-4 and TBZ-15 displayed stronger insecticidal activity against Ostrinia furnacalis (O. furnacalis) and Plutella xylostella (P. xylostella) than hexaflumuron, and TBZ-4 achieved better control efficacy than chlorbenzuron. Additionally, scanning electron microscopy observation and DFT/ESP calculations clarified their action mechanism. Toxicity prediction confirmed their safety to nontarget organisms. This work demonstrates TBZs as eco-friendly insecticides and highlights the value of computer-aided strategy for sustainable agrochemical development.