Abstract
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.
Highlights
OP insecticides bear a diverse group of chemical structures that exhibit a wide range of physicochemical properties, with their primary toxicological action arising from inhibition of acetylcholinesterase (AChE)[2]
The results show that the mode of action of compound XP-1408 is due to the synergistic actions of the suppression of cholinergic synaptic transmission, the blockage of K v and Nav channels, and AChE inhibitoion
The reaction conditions of the final product were optimized by using the synthesis of compound I-2 as a model reaction
Summary
OP insecticides bear a diverse group of chemical structures that exhibit a wide range of physicochemical properties, with their primary toxicological action arising from inhibition of acetylcholinesterase (AChE)[2]. The antennal lobe projection neurons (PNs) of Drosophila are the most cholinergic and receive cholinergic synaptic input, and fire spontaneously[20] It makes Drosophila whole-brain preparation as an ideal intact neural model to investigate the influences of chemical compounds on neural functions of insect CNS21. Inspired by the discovery of mode of action of isoxazoline insecticides[22, 23], we designed and synthesized two kinds of novel phosphorothioate and phosphoramidothioate derivatives containing diphenyl isoxazoline Their insecticidal activities against target pests (e.g., Spodoptera litura, Plutella xylostella, etc.) were not ideal at their assigned concentration, we found an interesting phenomenon. The results show that the mode of action of compound XP-1408 is due to the synergistic actions of the suppression of cholinergic synaptic transmission, the blockage of K v and Nav channels, and AChE inhibitoion
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
