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Existing insecticides have high toxicity towards non-target organisms, such as bees, limiting their practical use. This study utilized an active group splicing approach to create 41 new isoxazoline compounds (FSC1\u2013FSC41). Bioassays indicated that most compounds displayed potent insecticidal activity against Plutella xylostella and Spodoptera litura. Particularly, FSC36 exhibited the highest activity, with LC50 values of 0.84 mg\/L and 1.52 mg\/L against P. xylostella and S. litura, surpassing the commercial compound fluxametamide (1.53 mg\/L and 2.05 mg\/L). Acute oral toxicity tests on honey bees showed FSC36 to have an LD50 of 2.77 mg\/L, lower than fluralaner (0.19 mg\/L) and fluxametamide (0.92 mg\/L), overcoming the \u201chigh efficacy\u2013high toxicity\u201d challenge. This research offers a foundation for developing novel isoxazoline insecticides that are highly effective and environmentally friendly.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c09246","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:02:12Z","timestamp":1789542132000},"page":"30079-30089","source":"Crossref","is-referenced-by-count":0,"title":["Novel Isoxazoline\nAmide Derivatives with Diaryl Sulfide\nFragment as Potential Insecticides"],"prefix":"10.1021","volume":"74","author":[{"given":"Zhonglu","family":"You","sequence":"first","affiliation":[{"name":"Sichuan University of Arts and Science , , ,","place":["Dazhou, P. R. China, 635000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyi","family":"Sun","sequence":"additional","affiliation":[{"name":"Anhui Agricultural University , , ,","place":["Hefei, P. R. 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