Sep 2026· Journal of Agricultural and Food Chemistry· 0 citations· 36 references
Insect-Plant Interactions and Control
Abstract
A series of fluorine-containing pyrazole benzamide derivatives were designed and synthesized. Compound Z1 exhibited significantly higher activity against P. xylostella (LC50 = 0.203 mg/L) than that of ethiprole (LC50 = 2.88 mg/L). Compounds Z1, Z8, and Z20 showed over 13-fold higher activity against S. frugiperda (LC50 = 3.38, 2.72, and 2.18 mg/L) than ethiprole (LC50 = 53.6 mg/L). Furthermore, compounds Z1, Z4, and Z20 exhibited good activity against O. furnacalis (LC50 = 4.21, 3.20, and 3.30 mg/L, respectively), with over 7-fold higher potency than ethiprole (LC50 = 30.8 mg/L). SAR analysis indicated that smaller substituents favored the insecticidal activity. MD simulations and ELISA confirmed that Z1 and tigolaner both target GABA receptors. Transcriptomic analysis further revealed that Z1 treatment disrupted motor protein and neuroactive ligand–receptor interaction pathways, upregulated ELOVL7 and SCD to remodel membrane lipids, and activated GST-mediated detoxification. These multipathway perturbations collectively underpin the insecticidal mechanism of Z1.
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It is demonstrated that linker-free PROTACs can outperform traditional designs, marking a paradigm shift in PROTAC development for targeted protein degradation.
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A new machine-learning framework aims to improve the success rate of computational protein design while moving away from results that reproduce sequences found in nature.
