Design, synthesis, and insecticidal activity of dihydroagarofuran-based oxime ether analogs against Mythimna separata as potential insecticides.
Abstract
Background
Agricultural pests significantly reduce crop yields and threaten global food security. Chemical pesticides remain the primary means of pest control. In this study, celangulin V, a plant-derived insecticide, was used as a lead compound. Guided by three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling and based on the tricyclic scaffold of dihydroagarofuran, a series of dihydroagarofuran oxime ether derivatives were designed and synthesized, and their insecticidal activity against Mythimna separata was evaluated using a leaf-dip bioassay.
Results
Compounds 3g and 4g showed excellent activity, with median lethal concentration (LC50) values of 18 and 11 mg·L-1, respectively, compared with 9 mg L-1 for the reference insecticide fipronil under the same laboratory conditions, and up to 960-fold more potent than celangulin V. Symptomatological analysis revealed poisoning symptoms similar to those induced by celangulin V. Molecular docking suggested that compounds 3g and 4g may occupy a putative binding region of the modeled V-ATPase H subunit and form potential halogen-bonding interactions with nearby amino acid residues.
Conclusion
The structure-activity relationships of the dihydroagarofuran oxime ether derivatives were established and further elucidated using comparative molecular field analysis (CoMFA), providing valuable guidance for the rational design of novel insecticides. Among the compounds, compound 4g exhibited significant potential and can be regarded as a promising insecticidal candidate. © 2026 Society of Chemical Industry.