Insecticidal effects of oxazosulfyl result from synaptic inhibition by targeting the vesicular acetylcholine transporter.

Oxazosulfyl is the first insecticide in the sulfyl (alkylsulfone) class developed for rice protection. While the vesicular acetylcholine transporter (VAChT) has been proposed as its primary molecular target, its mode of action has not yet been extensively examined in major agricultural pests. In this study, we investigated the binding affinity of oxazosulfyl to VAChT derived from the brown planthopper (BPH), a significant rice pest, and evaluated the relationship between its insecticidal activity and binding affinity. Oxazosulfyl bound to VAChT, heterologously expressed in cultured cells, with a Kd of 1.7 nM. The displacement potency of its analogs strongly correlated with their insecticidal activity against BPH in a rice foliar spray test. Combined with the observation that oxazosulfyl blocks excitatory synaptic transmission in the cercal reflex circuit of the American cockroach, these results indicate that oxazosulfyl functions as a synaptic transmission inhibitor, exerting potent insecticidal activity against BPH, primarily through VAChT inhibition.