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Among them, diaryl thioether 2b-1 exhibited optimal trehalase inhibitory activity with 72.5% inhibition rate at 100 \u03bcM and a Ki value of 36.3 \u03bcM, superior to bifenox (56.5 \u03bcM). Insecticidal activity assay showed that compound 2b-1 displayed stronger insecticidal potency against Ostrinia furnacalis (LC50 = 34.7 mg\/L) than bifenox (LC50 = 61.2 mg\/L). Molecular docking and density functional theory (DFT) calculations proved 2b-1 formed abundant hydrogen bonds and \u03c0-sulfur interaction with key residues of OfTreh, accompanied by a lower energy gap and enhanced electrostatic potential distribution at the active sites. Transcriptomics further verified that 2b-1 disrupted energy metabolism, activated detoxification pathways, and interfered with cuticle remodeling of Ostrinia furnacalis larvae. Collectively, this work indicated that diaryl thioether 2b-1 could serve as a promising lead for developing novel trehalase-targeting insecticides.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c07520","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:02:00Z","timestamp":1790046120000},"page":"30561-30572","source":"Crossref","is-referenced-by-count":0,"title":["Structural Modification\nof Bifenox Derivatives: Discovery\nof Novel Diaryl Thioethers as Potent Insect Trehalase Inhibitors"],"prefix":"10.1021","volume":"74","author":[{"given":"Xining","family":"Sun","sequence":"first","affiliation":[{"name":"Shenyang Agricultural University , , , ,","place":["Shenyang, Liaoning, China, 110866"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Dalian University , , , ,","place":["Dalian, Liaoning, China, 116622"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjia","family":"Gao","sequence":"additional","affiliation":[{"name":"Dalian University of Technology , , , ,","place":["Dalian, Liaoning, China, 116024"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Shenyang Agricultural University , , , ,","place":["Shenyang, Liaoning, China, 110866"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Shenyang Agricultural University , , , ,","place":["Shenyang, Liaoning, China, 110866"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6536-752X","authenticated-orcid":true,"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Shenyang Agricultural University , , , ,","place":["Shenyang, Liaoning, China, 110866"]},{"name":"Biopesticide Engineering Technology Research Center Liaoning Province , , ,","place":["Shenyang, Liaoning, China, 110866"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9768-5496","authenticated-orcid":true,"given":"Tian","family":"Liu","sequence":"additional","affiliation":[{"name":"Dalian University of Technology , , , ,","place":["Dalian, Liaoning, China, 116024"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0647-9725","authenticated-orcid":true,"given":"Xinghai","family":"Li","sequence":"additional","affiliation":[{"name":"Shenyang Agricultural University , , , ,","place":["Shenyang, Liaoning, China, 110866"]},{"name":"Biopesticide Engineering Technology Research Center Liaoning Province , , ,","place":["Shenyang, Liaoning, China, 110866"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"issue":"27","key":"2026100711063163000_cit1","doi-asserted-by":"publisher","first-page":"15276","DOI":"10.1021\/acs.jafc.4c02841","article-title":"Design, Synthesis, and Acaricidal\/Insecticidal\nActivities of New Phenylpyrazole Derivatives Comprising an Imide Moiety","volume":"72","author":"Liu","year":"2024","journal-title":"J. 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