State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Key Laboratory of Natural Pesticide and Chemical Biology of the Ministry of Education, South China Agricultural University, Guangzhou, 510642, P.R. China.
School of Nuclear Technology and Chemistry & Biology, Hubei University of Science and Technology, Xianning, 437100, P.R. China.
Sci Rep. 2017 Jun 15;7(1):3617. doi: 10.1038/s41598-017-03663-3.
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 (K) channels and sodium (Na) 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.
有机磷（OP）杀虫剂在害虫防治中起着重要作用。由于对人类具有高毒性，许多 OP 杀虫剂已从市场上撤出。我们设计并合成了一种新型 OP 杀虫剂，旨在提供一种低成本、低毒性的杀虫剂。我们研究了 O,O-二乙基 O-(4-(5-苯基-4,5-二氢异恶唑-3-基)苯基)硫代磷酸酯（XP-1408）在黑腹果蝇中的作用方式。生物测定表明，XP-1408 在 50mg/L 的浓度下延迟了幼虫的发育。分子对接进入果蝇乙酰胆碱酯酶（AChE）和电压门控钠通道表明，XP-1408 适合它们的活性部位，并可能具有抑制作用。全细胞膜片钳记录表明，XP-1408 表现出协同作用，涉及到胆碱能突触传递的抑制以及电压门控钾（K）通道和钠（Na）通道的阻断。总之，XP-1408 的多种作用使其成为一种具有新型作用模式的 OP 杀虫剂的先导化合物。
