Fuente: PubMed "pollination" Pest Manag Sci. 2026 Mar 6. doi: 10.1002/ps.70708. Online ahead of print.ABSTRACTBACKGROUND: Spodoptera frugiperda (S. frugiperda) and Plutella xylostella (P. xylostella) are major constraints to staple and cruciferous crops, respectively, and have evolved widespread resistance to anthranilic amide insecticides. Isoxazolines, acting as γ-aminobutyric acid (GABA) receptor modulators, are promising alternatives for controlling resistant populations. However, many members of this class exhibit high toxicity toward ecologically important pollinators. Here, we report a series of new isoxazoline analogues featuring a 1,2,4-oxadiazole motif designed by a ring-closure strategy to the fluxametamide scaffold, and we systematically assess their insecticidal efficacy, honeybee toxicity, and interaction with receptors.RESULTS: Incorporation of a 1,2,4-oxadiazole moiety enabled the design, synthesis, and bioevaluation of 34 novel derivatives. Compound L1 displayed potent activity against P. xylostella, with a median lethal concentration (LC50) of 0.89 mg L-1. After chiral resolution, S-(+)-L1 showed markedly enhanced potency (LC50 = 0.69 mg L-1), being 159.36-fold more active than R-(-)-L1 (LC50 = 109.96 mg L-1) and comparable to fluxametamide (LC50 = 0.51 mg L-1). Notably, S-(+)-L1 exhibited substantially reduced acute contact toxicity to honeybees (LD50 = 4.58 μg a.i./bee) relative to fluxametamide (LD50 = 0.25 μg a.i./bee). Enzyme-linked immunosorbent assay (ELISA)-based assays and molecular docking suggested that S-(+)-L1 binds more favorably to the pest GABA receptor than its enantiomer, while the 1,2,4-oxadiazole unit specifically weakens hydrogen-bond interactions with the bee GABA receptor, thereby mitigating toxicity.CONCLUSION: S-(+)-L1 is identified as a selective lead combining high pesticidal potency with improved pollinator safety, suggesting ring-closure-enabled scaffold hopping as a viable strategy to retain on-target engagement while enhancing non-target compatibility. © 2026 Society of Chemical Industry.PMID:41793051 | DOI:10.1002/ps.70708