Pyrido[1,2‐ a ]pyrimidinone mesoionic compounds containing dithioacetal moiety: design, synthesis, insecticidal/antiviral activity and mechanism

Abstract BACKGROUND Bean aphid ( Aphis craccivora ) is one of the most destructive agricultural pests, causing direct harm by sucking plant sap and indirect damage by transmitting various plant viruses, such as potato virus Y (PVY). Extensive and prolonged use of neonicotinoid insecticides has led to severe resistance in A. craccivora . Therefore, there is an urgent need to develop new and highly effective insecticides to control aphids. RESULTS A series of pyrido[1,2‐ a ]pyrimidinone compounds containing a dithioacetal moiety were designed and synthesized, and their biological activities were evaluated. Compound J1 demonstrated a median lethal concentration (LC 50 ) of 3.51 μg/mL against A. craccivora , comparable with that of triflumezopyrim (LC 50 = 3.95 μg/mL). The 50% effective concentrations (EC 50 ) values for the anti‐PVY protective activity of compounds J1 and J18 were 264.55 and 225.45 μg/mL, respectively, better than those of ningnanmycin (EC 50 = 428.11 μg/mL) and vanisulfane (EC 50 = 309.46 μg/mL). The results of proteomic analysis, reactive oxygen species generation rate assays, and enzyme activity indicated that compound J1 may act on the central nervous system of A. craccivora , inducing mitochondrial damage in neurons and ultimately leading to pest mortality. In addition, compound J1 markedly enhanced the activity of defense enzymes and regulated the plant hormone signaling pathways in Nicotiana tabacum cv. k326, thereby strengthening the plant's defense response and disease resistance against PVY. CONCLUSION Compound J1 demonstrated potent aphicidal efficacy and remarkable anti‐PVY protective properties, offering novel insights for the integrated management of A. craccivora and the PVY they transmit. © 2025 Society of Chemical Industry.