Discovery and identification of O, O-diethyl O-(4-(5-phenyl-4, 5-dihydroisoxazol-3-yl) phenyl) phosphorothioate (XP-1408) as a novel mode of action of organophosphorus insecticides

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...

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Autores principales:	Zhigang Zeng, Ying Yan, Bingfeng Wang, Niu Liu, Hanhong Xu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7d65e9d0630b4311b18a3f009c92d75f
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spelling	oai:doaj.org-article:7d65e9d0630b4311b18a3f009c92d75f2021-12-02T12:32:37ZDiscovery and identification of O, O-diethyl O-(4-(5-phenyl-4, 5-dihydroisoxazol-3-yl) phenyl) phosphorothioate (XP-1408) as a novel mode of action of organophosphorus insecticides10.1038/s41598-017-03663-32045-2322https://doaj.org/article/7d65e9d0630b4311b18a3f009c92d75f2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03663-3https://doaj.org/toc/2045-2322Abstract 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.Zhigang ZengYing YanBingfeng WangNiu LiuHanhong XuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zhigang Zeng Ying Yan Bingfeng Wang Niu Liu Hanhong Xu Discovery and identification of O, O-diethyl O-(4-(5-phenyl-4, 5-dihydroisoxazol-3-yl) phenyl) phosphorothioate (XP-1408) as a novel mode of action of organophosphorus insecticides
description	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.
format	article
author	Zhigang Zeng Ying Yan Bingfeng Wang Niu Liu Hanhong Xu
author_facet	Zhigang Zeng Ying Yan Bingfeng Wang Niu Liu Hanhong Xu
author_sort	Zhigang Zeng
title	Discovery and identification of O, O-diethyl O-(4-(5-phenyl-4, 5-dihydroisoxazol-3-yl) phenyl) phosphorothioate (XP-1408) as a novel mode of action of organophosphorus insecticides
title_short	Discovery and identification of O, O-diethyl O-(4-(5-phenyl-4, 5-dihydroisoxazol-3-yl) phenyl) phosphorothioate (XP-1408) as a novel mode of action of organophosphorus insecticides
title_full	Discovery and identification of O, O-diethyl O-(4-(5-phenyl-4, 5-dihydroisoxazol-3-yl) phenyl) phosphorothioate (XP-1408) as a novel mode of action of organophosphorus insecticides
title_fullStr	Discovery and identification of O, O-diethyl O-(4-(5-phenyl-4, 5-dihydroisoxazol-3-yl) phenyl) phosphorothioate (XP-1408) as a novel mode of action of organophosphorus insecticides
title_full_unstemmed	Discovery and identification of O, O-diethyl O-(4-(5-phenyl-4, 5-dihydroisoxazol-3-yl) phenyl) phosphorothioate (XP-1408) as a novel mode of action of organophosphorus insecticides
title_sort	discovery and identification of o, o-diethyl o-(4-(5-phenyl-4, 5-dihydroisoxazol-3-yl) phenyl) phosphorothioate (xp-1408) as a novel mode of action of organophosphorus insecticides
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/7d65e9d0630b4311b18a3f009c92d75f
work_keys_str_mv	AT zhigangzeng discoveryandidentificationofoodiethylo45phenyl45dihydroisoxazol3ylphenylphosphorothioatexp1408asanovelmodeofactionoforganophosphorusinsecticides AT yingyan discoveryandidentificationofoodiethylo45phenyl45dihydroisoxazol3ylphenylphosphorothioatexp1408asanovelmodeofactionoforganophosphorusinsecticides AT bingfengwang discoveryandidentificationofoodiethylo45phenyl45dihydroisoxazol3ylphenylphosphorothioatexp1408asanovelmodeofactionoforganophosphorusinsecticides AT niuliu discoveryandidentificationofoodiethylo45phenyl45dihydroisoxazol3ylphenylphosphorothioatexp1408asanovelmodeofactionoforganophosphorusinsecticides AT hanhongxu discoveryandidentificationofoodiethylo45phenyl45dihydroisoxazol3ylphenylphosphorothioatexp1408asanovelmodeofactionoforganophosphorusinsecticides
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Discovery and identification of O, O-diethyl O-(4-(5-phenyl-4, 5-dihydroisoxazol-3-yl) phenyl) phosphorothioate (XP-1408) as a novel mode of action of organophosphorus insecticides

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