New Mesoionic Pyrido[1,2‑a] Pyrimidines Containing Oxime Esters against Megoura japonica with Better Safety to Pollinating Insects

The selectivity of pesticides for harmful insects versus beneficial organisms has long been a critical issue in agriculture. Pyrido[1,2-a] pyrimidine mesoionics have been widely demonstrated to effectively control a diverse range of insect pests. However, many of their analogues have exhibited high toxicity to bees. Herein, we report a new analogue of pyrido[1,2-a] pyrimidines designed through oxime ester functionalization. Biological activity tests revealed that these derivatives possess potential aphidicidal activity. Compound WZ18 demonstrates a median lethal concentration (LC50) of 1.73 μg/mL, slightly lower than that of the positive control triflumezopyrim (TFM) (LC50 = 3.05 μg/mL). Notably, WZ18 shows significantly reduced toxicity in acute contact experiments on honey bees (Apis mellifera Ligustica Spinola). Its median lethal dose (LD50) is 6.25 μg a.i./bee, compared to 0.06 μg a.i./bee for TFM. Investigations into the penetration mechanism indicate that the insecticidal activity of WZ18 is primarily due to its systemic property. Moreover, proteomic analyses suggest that WZ18 may interfere with the nervous system of pests. Molecular docking and molecular dynamics simulations further support that WZ18 likely shares a similar mechanism of action with TFM. This study provides a valuable foundation for the development of mesoionic insecticides that are safer for nontarget organisms.