{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:10:44Z","timestamp":1789567844316,"version":"build-2803163510"},"reference-count":39,"publisher":"American Chemical Society (ACS)","issue":"36","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFA0907903"],"award-info":[{"award-number":["2020YFA0907903"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32372597"],"award-info":[{"award-number":["32372597"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The resistance to pyrethroid insecticides is becoming increasingly severe, while the number of insecticides with negative cross-resistance (NCR) remains extremely limited. Thus, the development of novel targets and candidate compounds is urgently required. To exploit NCR insecticides targeting the voltage-gated sodium channel (VGSC), structural modifications of the B and C rings were performed on the lead compound 6i, leading to the synthesis of a series of derivatives. Bioassays, electrophysiological experiments and cytotoxicity assays demonstrated that the derivative LC-2 exhibited insecticidal activity against multiple insect pests. Notably, LC-2 showed significant NCR against pyrethroid-resistant Aedes aegypti (resistance ratio = 0.12). Its mode of action involves targeting the insect VGSC and impairing the function of the channel\u2019s fast inactivation gate. Meanwhile, this compound presented low toxicity to mammalian cells. In conclusion, this study identified a novel compound LC-2 with NCR to pyrethroids, multi-pest insecticidal activity, which provides a theoretical basis and material support for insecticide resistance management and the development of low-toxic NCR insecticides.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c09268","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:36:19Z","timestamp":1788460579000},"page":"28362-28372","source":"Crossref","is-referenced-by-count":0,"title":["Targeting Voltage-Gated\nSodium Channels: Discovery\nof a Multi-Pest Insecticidal Activity Compound with Negative Cross-Resistance\nto Pyrethroid Resistance"],"prefix":"10.1021","volume":"74","author":[{"given":"Jiaojiao","family":"Luo","sequence":"first","affiliation":[{"name":"Northwest A & F University , , ,","place":["Yangling, Shaanxi, PR China, 712100"]},{"name":"Northwest A & F University , , ,","place":["Yangling, Shaanxi, PR China, 712100"]},{"name":"Henan University of Urban Construction , , ,","place":["Pingdingshan, Henan, China, 467036"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3130-6099","authenticated-orcid":true,"given":"Ding","family":"Li","sequence":"additional","affiliation":[{"name":"Northwest A & F University , , ,","place":["Yangling, Shaanxi, PR China, 712100"]},{"name":"Northwest A & F University , , , ,","place":["Xianyang, Shaanxi, P. R China, 712100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzheng","family":"Du","sequence":"additional","affiliation":[{"name":"Northwest A & F University , , ,","place":["Yangling, Shaanxi, PR China, 712100"]},{"name":"Northwest A & F University , , ,","place":["Yangling, Shaanxi, PR China, 712100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lele","family":"Feng","sequence":"additional","affiliation":[{"name":"Northwest A & F University , , ,","place":["Yangling, Shaanxi, PR China, 712100"]},{"name":"Northwest A & F University , , ,","place":["Yangling, Shaanxi, PR China, 712100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wangyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Northwest A & F University , , ,","place":["Yangling, Shaanxi, PR China, 712100"]},{"name":"Northwest A & F University , , ,","place":["Yangling, Shaanxi, PR China, 712100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9198-4057","authenticated-orcid":true,"given":"Yayun","family":"Zuo","sequence":"additional","affiliation":[{"name":"Northwest A & F University , , ,","place":["Yangling, Shaanxi, PR China, 712100"]},{"name":"Northwest A & F University , , ,","place":["Yangling, Shaanxi, PR China, 712100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8091-7630","authenticated-orcid":true,"given":"Zhaonong","family":"Hu","sequence":"additional","affiliation":[{"name":"Northwest A & F University , , ,","place":["Yangling, Shaanxi, PR China, 712100"]},{"name":"Northwest A & F University , , ,","place":["Yangling, Shaanxi, PR China, 712100"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"2026091609091328100_cit1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.08347","article-title":"The global distribution of the arbovirus\nvectors Aedes aegypti and Ae","volume":"4","author":"Kraemer","year":"2015","journal-title":"albopictus. eLife"},{"issue":"1","key":"2026091609091328100_cit2","doi-asserted-by":"publisher","first-page":"49","DOI":"10.3390\/insects14010049","article-title":"Global distribution\nof Aedes aegypti and Aedes albopictus in a climate change scenario\nof regional rivalry","volume":"14","author":"Laporta","year":"2023","journal-title":"Insects"},{"issue":"1","key":"2026091609091328100_cit3","doi-asserted-by":"publisher","first-page":"3418","DOI":"10.1038\/s41467-025-58609-5","article-title":"The overlapping global distribution\nof dengue, chikungunya, Zika and yellow fever","volume":"16","author":"Lim","year":"2025","journal-title":"Nat. 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Biol."},{"key":"2026091609091328100_cit29","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1007\/s004380050608","article-title":"Point mutations in\nthe Drosophila para voltage-gated sodium channel\ngene confer resistance to DDT and pyrethroid insecticides","volume":"256","author":"Pittendrigh","year":"1997","journal-title":"Mol. Gen. Genet."},{"key":"2026091609091328100_cit30","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.pestbp.2003.09.007","article-title":"Hypersusceptibility\nto deltamethrin in parats21 DDT resistant Drosophila melanogaster","volume":"78","author":"Pedra","year":"2004","journal-title":"Pestic. Biochem. 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