Innovative pyrido[1,2-a]pyrimidine-based cinnamic acid derivatives against Sogatella furcifera with better biosafety to pollinators.

BACKGROUND: Sogatella furcifera, commonly known as white-backed planthopper, is a highly threatening migratory pest that feeds on rice and can transmit phytoviruses. Recently, mesoionic insecticides, exemplified by triflumezopyrim (TFM), have proven effective in managing such pests. Nevertheless, available data indicate that TFM remains highly toxic to ecologically important pollinators. Herein, the development of a class of pyrido[1,2-a]pyrimidine-based cinnamic acid analogs, their insecticidal activity, modes of action, and toxicity to bees are disclosed.

RESULTS: A total of 37 novel pyrido[1,2-a]pyrimidine mesoionics (W1-W37) incorporating cinnamic amides were systematically designed, synthesized and evaluated for their insecticidal performance. Compound W19 was found to be the most potent, achieving 100% mortality in S. furcifera at both concentrations of 100.00 μg mL-1 and 10.00 μg mL-1, with a median lethal concentration (LC50) of 1.34 μg mL-1. Notably, despite having a slightly higher LC50 value than the positive control TFM (LC50 = 0.21 μg mL-1), W19 exhibited significantly lower acute exposure toxicity (LD50 = 62.37 μg a.i./bee) to Apis mellifera in comparison to TFM (LD50 = 0.51 μg a.i./bee). Employing a combination of proteomics, enzyme activity testing, quantitative real-time PCR and molecular docking technologies, it is proposed that W19 functions as a modulator of nicotinic acetylcholine receptor (nAChR). The reduced risk to honeybees is likely attributed to W19's weaker and less frequent binding to bee nAChR.

CONCLUSION: Our study shows that leveraging cinnamic acid derivatives into the design of mesoionic insecticides is expected to lead to the discovery of more selective agrochemicals and improve their compatibility with nontarget organisms. © 2025 Society of Chemical Industry.