Megoura crassicauda, a sap-feeder on legumes, remains a persistent threat, yet current control depends largely on neonicotinoids that pose serious risks to beneficial pollinators. We herein describe a set of new pyrido[1,2-a]pyrimidinone derivatives bearing a carbamate moiety attached via a methylene spacer at the 2-position. Insecticidal bioassays identified H3 as the most potent analogue against M. crassicauda, comparable to the commercial standard TFM. Encouragingly, H3 exhibited remarkably low toxicity to honeybees, with acute oral and contact LD50 values of 24.0 and 35.1 μg a.i./bee, respectively, which were markedly higher than those of TFM. Mechanistic studies combining proteomics, enzymatic assays, and molecular docking consistently suggested that H3 disrupts neuronal homeostasis via interfering with nAChR and AChE activity, leading to insect mortality. This work provides a promising and bee-safe lead for sustainable pest management, offering a new molecular template for the development of highly selective insecticides.
Qingqing Ma, Shang Wu, Luoman Zhang et al.· Journal of Agricultural and...· 0 citations
4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a vital target for herbicide development. A series of pyrazole-quinoxaline conjugates were designed and synthesized via scaffold hopping and structural optimization. Bioassays revealed that B9 exhibited potent inhibitory activity against Arabidopsis thaliana HPPD (AtHPPD) with an IC50 of 0.11 μM, outperforming mesotrione (0.22 μM) and topramezone (0.48 μM). B18 achieved 100% control over six weeds at 75 g a.i./ha and retained full efficacy against three broadleaf weeds even at 18.75 g a.i./ha. Furthermore, B18 produced less than 20% injury to rice, wheat, cotton, and peanut at 150 g a.i./ha, exhibiting superior crop safety to topramezone (47%-72%). Molecular docking elucidated the binding mechanism of B18 with AtHPPD via Fe2+ coordination, π-π interactions, and hydrogen bonds. Fluorescence titration and microscale thermophoresis assays further confirmed strong binding of B9 and B18 to AtHPPD. This study demonstrated that B18 is a promising, safe, and efficient HPPD-inhibiting herbicide candidate.
Li Liu, Mei Zhang, Lingling Wang et al.· Journal of Agricultural and...· 0 citations
