Organophosphorus (OP) insecticides play an important role in pest control. Many OP insecticides have been removed from the market because of their high toxicity to humans. We designed and synthesized a new OP insecticide with the goal of providing a low cost, and less toxic insecticide. The mode of action of O, O-diethyl O-(4-(5-phenyl-4, 5-dihydroisoxazol-3-yl) phenyl) phosphorothioate (XP-1408) was studied in Drosophila melanogaster. Bioassays showed that XP-1408 at a concentration of 50 mg/L delayed larval development. Molecular docking into Drosophila acetylcholinesterase (AChE) and voltage-gated sodium channels suggested that XP-1408 fitted into their active sites and could be inhibitory. Whole-cell patch clamp recordings indicated that XP-1408 exhibited synergistic effects involving the inhibition of cholinergic synaptic transmission and blockage of voltage-gated potassium (Kv) channels and sodium (Nav) channels. In conclusion, the multiple actions of XP-1408 rendered it as a lead compound for formulating OP insecticides with a novel mode of action.

NICOTINIC ACETYLCHOLINE-RECEPTOR; CELL-PROLIFERATION; GROWTH-INHIBITION; COMMON MECHANISM; K+ CHANNELS; IN-VIVO; EXPRESSION; POTASSIUM; EXPOSURE; DYSFUNCTIONS

Hubei University of Science and Technology; South China Agricultural University