{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T14:27:20Z","timestamp":1793802440022,"version":"4.6.1"},"reference-count":39,"publisher":"American Chemical Society (ACS)","issue":"43","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100007917","name":"Agricultural Research Service","doi-asserted-by":"publisher","award":["59- 6060-5-001"],"award-info":[{"award-number":["59- 6060-5-001"]}],"id":[{"id":"10.13039\/100007917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000199","name":"U.S. Department of Agriculture","doi-asserted-by":"publisher","award":["2025-70029-44026"],"award-info":[{"award-number":["2025-70029-44026"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Huanglongbing (HLB), caused by the phloem-restricted bacterium Candidatus Liberibacter (CLas) vectored by the Asian Citrus Psyllid (Hemiptera: Psyllidae; ACP), has led to billion-dollar losses in the global citrus industry. Pharmacological inhibition of inward rectifier potassium (Kir) channels leads to acute mortality and inhibits CLas acquisition by ACP through salivary gland-directed antifeedant activity. Here, we designed a series of analogs that shifted synthetic Kir inhibitors toward a more biogenic chemical space through systematic modification of VU730 (C17H19N3O2). Analog 7c, which contains a benzimidazole core as the northern fragment, caused \u223c50% morbidity at 10 ng\/cm2 48 h after tarsal contact exposure and had greater efficacy to feeding disruption than VU730. These data define tractable structural features for identification of natural Kir inhibitors that may possess toxic and antifeedant properties and identify VU730 and 7c as priorities for development of novel mechanism insecticides for HLB prevention.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c12137","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:02:05Z","timestamp":1792666925000},"page":"34385-34397","source":"Crossref","is-referenced-by-count":0,"title":["Ligand-Based Scaffold\nHopping of VU730 Identifies\nNatural Product-Inspired Analogs with Insecticidal and Antifeedant\nActivity against Asian Citrus Psyllid,\n                    <i>Diaphorina citri<\/i>"],"prefix":"10.1021","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4973-9645","authenticated-orcid":true,"given":"Alexandra","family":"Cremades","sequence":"first","affiliation":[{"name":"University of Florida , , , ,","place":["Gainesville, Florida, United States, 32610"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh Chandra V.A.R.","family":"Annam","sequence":"additional","affiliation":[{"name":"University of Mississippi , , , ,","place":["University, Mississippi, United States, 38677"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flinn","family":"O\u2019Hara","sequence":"additional","affiliation":[{"name":"University of Florida , , , ,","place":["Gainesville, Florida, United States, 32610"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabil","family":"Killiny","sequence":"additional","affiliation":[{"name":"University of Florida , , , ,","place":["Lake Alfred, Florida, United States, 33850"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bita","family":"Valizadeh","sequence":"additional","affiliation":[{"name":"University of Nebraska , , , ,","place":["Lincoln, Nebraska, United States, 68583"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troy D.","family":"Anderson","sequence":"additional","affiliation":[{"name":"University of Nebraska , , , ,","place":["Lincoln, Nebraska, United States, 68583"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukasz L.","family":"Stelinski","sequence":"additional","affiliation":[{"name":"University of Florida , , , ,","place":["Lake Alfred, Florida, United States, 33850"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7047-5373","authenticated-orcid":true,"given":"Amar G.","family":"Chittiboyina","sequence":"additional","affiliation":[{"name":"University of Mississippi , , , ,","place":["University, Mississippi, United States, 38677"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1055-8326","authenticated-orcid":true,"given":"Daniel R.","family":"Swale","sequence":"additional","affiliation":[{"name":"University of Florida , , , ,","place":["Gainesville, Florida, United States, 32610"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"issue":"1","key":"2026110408124341100_cit1","doi-asserted-by":"publisher","DOI":"10.1093\/jipm\/pmz037","article-title":"The Economic Challenges of Dealing with Citrus Greening:\nThe Case of Florida","volume":"11","author":"Singerman","year":"2020","journal-title":"J. Integr. Pest Manage."},{"issue":"10","key":"2026110408124341100_cit2","doi-asserted-by":"publisher","first-page":"2725","DOI":"10.1002\/ps.5382","article-title":"Chemical\ninhibition of Kir channels\nreduces salivary secretions and phloem feeding of the cotton aphid","volume":"75","author":"Li","year":"2019","journal-title":"Pest Manage. Sci."},{"key":"2026110408124341100_cit3","doi-asserted-by":"publisher","DOI":"10.1016\/j.pestbp.2022.105174","article-title":"Profile\nof commercialized aphicides\non the survivorship and feeding behavior of the cotton aphid, Aphis\ngossypii","volume":"186","author":"O\u2019Hara","year":"2022","journal-title":"Pest. Biochem. Phys."},{"issue":"1","key":"2026110408124341100_cit4","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1002\/ps.7188","article-title":"Catalyzing systemic movement of inward\nrectifier potassium channel inhibitors for antifeedant activity against\nthe cotton aphid, Aphis gossypii (Glover)","volume":"79","author":"O\u2019Hara","year":"2023","journal-title":"Pest\nManage. Sci."},{"key":"2026110408124341100_cit5","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.pestbp.2016.11.005","article-title":"Role of inward rectifier\npotassium channels in salivary gland function and sugar feeding of\nthe fruit fly, Drosophila melanogaster","volume":"141","author":"Swale","year":"2017","journal-title":"Pest. Biochem. Phys."},{"issue":"4845","key":"2026110408124341100_cit6","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1126\/science.3344436","article-title":"Salivary gland lysates from the sand\nfly Lutzomyia\nlongipalpis enhance Leishmania infectivity","volume":"239","author":"Titus","year":"1988","journal-title":"Science"},{"issue":"3","key":"2026110408124341100_cit7","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1099\/00207713-44-3-379","article-title":"The phloem-limited bacterium of greening\ndisease of citrus is a member of the alpha subdivision of the Proteobacteria","volume":"44","author":"Jagoueix","year":"1994","journal-title":"Int. J. Syst. Bacteriol."},{"issue":"1","key":"2026110408124341100_cit8","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1111\/j.1570-7458.2009.00937.x","article-title":"Characterization of electrical penetration\ngraphs of\nthe Asian citrus psyllid, Diaphorina citri, in sweet orange seedlings","volume":"134","author":"Bonani","year":"2010","journal-title":"Entomol. Exp.\nAppl."},{"issue":"1","key":"2026110408124341100_cit9","doi-asserted-by":"publisher","DOI":"10.1186\/s12870-019-2114-2","article-title":"Long-term,\nsustained feeding by Asian citrus psyllid disrupts salicylic acid\nhomeostasis in sweet orange","volume":"19","author":"Ibanez","year":"2019","journal-title":"BMC Plant Biol."},{"issue":"4","key":"2026110408124341100_cit10","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1093\/jme\/tjaa015","article-title":"Small-Molecule\nInhibitors of Inward Rectifier Potassium (Kir) Channels Reduce Bloodmeal\nFeeding and Have Insecticidal Activity Against the Horn Fly (Diptera:\nMuscidae)","volume":"57","author":"Li","year":"2020","journal-title":"J. Med. Entomol."},{"issue":"2","key":"2026110408124341100_cit11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007153","article-title":"Inward rectifier\npotassium (Kir) channels mediate salivary gland function and blood\nfeeding in the lone star tick, Amblyomma americanum","volume":"13","author":"Li","year":"2019","journal-title":"PLoS Neglected Trop. Dis."},{"issue":"Pt 1","key":"2026110408124341100_cit12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2023.126545","article-title":"ATP-sensitive\ninward rectifier potassium channels regulate secretion of pro-feeding\nsalivary proteins in the lone star tick (Amblyomma americanum)","volume":"253","author":"Li","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"issue":"1","key":"2026110408124341100_cit13","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03222-1","article-title":"ATP-sensitive inward\nrectifier potassium channels reveal functional linkage between salivary\ngland function and blood feeding in the mosquito, Aedes aegypti","volume":"5","author":"Li","year":"2022","journal-title":"Commun. Bio."},{"issue":"13","key":"2026110408124341100_cit14","doi-asserted-by":"publisher","first-page":"10892","DOI":"10.1021\/acs.jafc.5c17254","article-title":"Inward Rectifier\nPotassium (Kir) Channel Inhibitors Protect Citrus from the Asian Citrus\nPsyllid by Inducing Toxicity and Inhibition of Feeding","volume":"74","author":"O\u2019Hara","year":"2026","journal-title":"J. Agric. Food Chem."},{"issue":"11","key":"2026110408124341100_cit15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0110772","article-title":"Discovery\nand characterization of a potent and selective\ninhibitor of Aedes aegypti inward rectifier potassium channels","volume":"9","author":"Raphemot","year":"2014","journal-title":"PLoS One"},{"key":"2026110408124341100_cit16","doi-asserted-by":"publisher","DOI":"10.1038\/srep36954","article-title":"An insecticide resistance-breaking mosquitocide\ntargeting inward rectifier potassium channels in vectors of Zika virus\nand malaria","volume":"6","author":"Swale","year":"2016","journal-title":"Sci. Rep."},{"issue":"1","key":"2026110408124341100_cit17","doi-asserted-by":"publisher","DOI":"10.1186\/s12985-023-02104-0","article-title":"Potassium ion channels\nas a molecular target to reduce virus infection and mortality of honey\nbee colonies","volume":"20","author":"Fellows","year":"2023","journal-title":"Virol. J."},{"issue":"1","key":"2026110408124341100_cit18","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-09448-y","article-title":"ATP-sensitive\ninwardly rectifying\npotassium channel regulation of viral infections in honey bees","volume":"7","author":"O\u2019Neal","year":"2017","journal-title":"Sci. Rep."},{"key":"2026110408124341100_cit19","doi-asserted-by":"publisher","DOI":"10.1016\/j.pestbp.2025.106521","article-title":"Trends\nin insecticide discovery: A review, analysis and perspective","volume":"213","author":"Sparks","year":"2025","journal-title":"Pestic. Biochem. Physiol."},{"key":"2026110408124341100_cit20","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.pestbp.2019.07.001","article-title":"Perspectives\non new strategies for the identification and development of insecticide\ntargets","volume":"161","author":"Swale","year":"2019","journal-title":"Pestic. Biochem. Physiol."},{"issue":"4","key":"2026110408124341100_cit21","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1002\/ps.4336","article-title":"Lead generation\nin crop protection research: a portfolio approach to agrochemical\ndiscovery","volume":"73","author":"Loso","year":"2017","journal-title":"Pest Manage. Sci."},{"key":"2026110408124341100_cit22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1021\/bk-2017-1264.ch001","volume-title":"Advances in Agrochemicals:\nIon Channels and G Protein-Coupled Receptors (GPCRs) as Targets for\nPest Control","author":"Sparks","year":"2017"},{"issue":"1","key":"2026110408124341100_cit23","doi-asserted-by":"publisher","DOI":"10.1186\/s12870-021-03389-5","article-title":"Salicylic\nacid mediated immune response of Citrus sinensis to varying frequencies of herbivory\nand pathogen inoculation","volume":"22","author":"Ibanez","year":"2022","journal-title":"BMC Plant Biol."},{"issue":"3","key":"2026110408124341100_cit24","doi-asserted-by":"publisher","first-page":"832","DOI":"10.21273\/HORTSCI.41.3.832","article-title":"US-812 citrus rootstock","volume":"41","author":"Bowman","year":"2006","journal-title":"HortScience"},{"issue":"1","key":"2026110408124341100_cit25","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1093\/jmedent\/45.1.82","article-title":"Susceptibility of Aedes aegypti, Culex quinquefasciatus\nSay, and Anopheles quadrimaculatus Say to 19 pesticides with different\nmodes of action","volume":"45","author":"Pridgeon","year":"2008","journal-title":"J. Med. Entomol."},{"issue":"1","key":"2026110408124341100_cit26","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1002\/ps.6004","article-title":"Control efficacy\nand joint toxicity of thiamethoxam mixed with spirotetramat against\nthe Asian citrus psyllid, Diaphorina citri Kuwayama","volume":"77","author":"Tang","year":"2021","journal-title":"Pest Manage. Sci."},{"issue":"1","key":"2026110408124341100_cit27","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.pestbp.2004.06.003","article-title":"Synergistic and\nantagonistic effects of atrazine on\nthe toxicity of organophosphorodithioate and organophosphorothioate\ninsecticides to Chironomus tentans (Diptera: Chironomidae)","volume":"80","author":"Anderson","year":"2004","journal-title":"Pestic. Biochem. Phys."},{"key":"2026110408124341100_cit28","doi-asserted-by":"publisher","DOI":"10.1016\/j.pestbp.2022.105271","article-title":"Acute toxicity\nof atrazine, alachlor,\nand chlorpyrifos mixtures to honey bees","volume":"188","author":"Fellows","year":"2022","journal-title":"Pestic.\nBiochem. Phys."},{"issue":"1","key":"2026110408124341100_cit29","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1002\/(Sici)1096-9063(199901)55:1&lt;11::Aid-Ps850&gt;3.3.Co;2-W","article-title":"Increased activity\nassociated with reduced sensitivity\nof acetylcholinesterase in organophosphate-resistant greenbug, (Homoptera:\nAphididae)","volume":"55","author":"Zhu","year":"1999","journal-title":"Pestic. Sci."},{"issue":"7","key":"2026110408124341100_cit30","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image\nto ImageJ: 25 years of\nimage analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"issue":"7","key":"2026110408124341100_cit31","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image\nanalysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"2026110408124341100_cit32","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1111\/j.1570-7458.1985.tb03517.x","article-title":"Membrane\npotentials as an indication for plant cell penetration by aphid stylets","volume":"38","author":"Tjallingii","year":"1985","journal-title":"Entomol. Exp. Appl."},{"key":"2026110408124341100_cit33","first-page":"89","article-title":"Continuous Recording of Stylet Penetration Activities","volume-title":"Aphid-Plant Genotype Interactions","author":"Tjallingii","year":"1990"},{"issue":"1","key":"2026110408124341100_cit34","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1111\/j.1570-7458.2009.00937.x","article-title":"Characterization\nof electrical penetration graphs of\nthe Asian citrus psyllid, Diaphorina citri, in sweet orange seedlings","volume":"134","author":"Bonani","year":"2010","journal-title":"Entomol. Exp.\nAppl."},{"issue":"2","key":"2026110408124341100_cit35","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1111\/j.1570-7458.1994.tb01813.x","article-title":"Aphid activities\nduring sieve element punctures","volume":"72","author":"Prado","year":"1994","journal-title":"Entomol. Exp.\nAppl."},{"key":"2026110408124341100_cit36","doi-asserted-by":"publisher","DOI":"10.1038\/srep42717","article-title":"SwissADME: a free web tool to evaluate\npharmacokinetics, drug-likeness and medicinal chemistry friendliness\nof small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"issue":"13","key":"2026110408124341100_cit37","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26133811","article-title":"New Insights into the\nDegradation Path of Deltamethrin","volume":"26","author":"Aiello","year":"2021","journal-title":"Molecules"},{"key":"2026110408124341100_cit38","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.ibmb.2014.12.005","article-title":"The structural sheath protein of aphids is required\nfor phloem feeding","volume":"57","author":"Will","year":"2015","journal-title":"Insect Biochem. Mol. Biol."},{"issue":"5","key":"2026110408124341100_cit39","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1603\/EC10123","article-title":"Transmission parameters\nfor Candidatus liberibacter asiaticus by Asian citrus psyllid (Hemiptera:\nPsyllidae)","volume":"103","author":"Pelz-Stelinski","year":"2010","journal-title":"J. Econ. Entomol."}],"container-title":["Journal of Agricultural\nand Food Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jafc.6c12137","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/doi\/10.1021\/acs.jafc.6c12137\/68939872\/acs.jafc.6c12137.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/doi\/10.1021\/acs.jafc.6c12137\/68939872\/acs.jafc.6c12137.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T13:43:44Z","timestamp":1793799824000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jafcau\/article\/74\/43\/34385\/5455981\/Ligand-Based-Scaffold-Hopping-of-VU730-Identifies"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,22]]},"references-count":39,"journal-issue":{"issue":"43","published-online":{"date-parts":[[2026,10,22]]},"published-print":{"date-parts":[[2026,11,4]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jafc.6c12137","relation":{},"ISSN":["0021-8561","1520-5118"],"issn-type":[{"value":"0021-8561","type":"print"},{"value":"1520-5118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,22]]}}}