Development of New Spiro Insecticides against White-Backed Planthoppers with Multitarget Impact

The invasive white-backed planthopper (WBP) poses a severe threat to global rice crop security, and most populations have developed significant resistance to neonicotinoids. Although these species remain sensitive to mesoionic triflumezopyrim (TFM), both neonicotinoids and TFM are hazardous to pollinating insects. Herein, we disclose a series of new spirocompounds designed via isosteric ring replacement of scaffold hopping. Of these, spirocyclic molecule A11 exhibits satisfactory biosafety to bees (LD₅₀ > 11.0 μg a.i./bee) and comparable efficacy (LC₅₀ = 11.0 μg/mL) against WBPs to that of spirotetramat (LC₅₀ = 11.6 μg/mL). Proteomics, quantitative Real-Time PCR, and enzyme activity assay experiments collaboratively verify the mode of action of A11 being a pest Acetyl-CoA Carboxylase Inhibitor. Noteworthily, the suppression of pyruvate carboxylase in WBP by spiro compounds is observed for the first time, which implies a multitarget effect of these insecticides on key Enzymes involved in tricarboxylic acid cycle. This impact enables effective inhibition of lipid biosynthesis pathways in WBPs, ultimately leading to the death of the pests. We believe this study provides valuable insights into the molecular basis of spiro substances on WBPs.

acetyl-CoA carboxylase; insecticide; proteomics; pyruvate carboxylase; spiro-compound.