{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:58:26Z","timestamp":1790776706289,"version":"4.1.0"},"reference-count":40,"publisher":"American Chemical Society (ACS)","issue":"38","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100012554","name":"Hubei Provincial Department of Education","doi-asserted-by":"publisher","award":["2024CSA063"],"award-info":[{"award-number":["2024CSA063"]}],"id":[{"id":"10.13039\/100012554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFE0214300"],"award-info":[{"award-number":["2024YFE0214300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["CCNU24JCPT023"],"award-info":[{"award-number":["CCNU24JCPT023"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["CCNU24JCPT029"],"award-info":[{"award-number":["CCNU24JCPT029"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Synthetic auxin herbicides (SAHs) with pyridinecarboxylate scaffolds are valued for their high efficacy and favorable safety, yet their limited structural diversity has constrained further development. In this study, we analyzed sequence variations in TIR1\/AFBs among different species and employed a pocket-oriented molecular design strategy to synthesize pyridinecarboxylate derivatives bearing novel benzene-fused six-membered ring frameworks. Through systematic structural optimization, we identified compound 8o, which showed outstanding herbicidal activity against many weeds at 3.75 g ai\/ha and high crop safety at 30 g ai\/ha. What\u2019s more, the interaction between protein AFB5 and IAA was stronger in the presence of compound 8o (Kd = 0.97 \u03bcM) than that with clopyralid (Kd = 7.20 \u03bcM) or halauxifen-methyl (Kd = 3.96 \u03bcM). Molecular simulations suggested that this enhanced activity may arise from a T\u2212\u03c0 interaction between 8o and Phe127. These results suggest that naphthyl rings as promising frameworks for the development of next-generation SAHs.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c01648","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T08:02:27Z","timestamp":1789977747000},"page":"29898-29908","source":"Crossref","is-referenced-by-count":0,"title":["Pocket-Oriented\nDesign of Benzene-Fused Pyridinecarboxylates\nas Potent Synthetic Auxin Herbicides"],"prefix":"10.1021","volume":"74","author":[{"given":"Wen-Yi","family":"Yang","sequence":"first","affiliation":[{"name":"Central China Normal University , , ,","place":["Wuhan, P.R. China, 430079"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Xiang","family":"Meng","sequence":"additional","affiliation":[{"name":"Central China Normal University , , ,","place":["Wuhan, P.R. China, 430079"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ting","family":"Wang","sequence":"additional","affiliation":[{"name":"Central China Normal University , , ,","place":["Wuhan, P.R. China, 430079"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"Central China Normal University , , ,","place":["Wuhan, P.R. China, 430079"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5627-3708","authenticated-orcid":true,"given":"Hong-Yan","family":"Lin","sequence":"additional","affiliation":[{"name":"Central China Normal University , , ,","place":["Wuhan, P.R. China, 430079"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Ting","family":"Hu","sequence":"additional","affiliation":[{"name":"Central China Normal University , , ,","place":["Wuhan, P.R. China, 430079"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wishwajith","family":"Kandegama","sequence":"additional","affiliation":[{"name":"Wayamba University of Sri Lanka , , Makandura, , ,","place":["Gonawila, North Western Province, Sri Lanka, 60170"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangqing","family":"Dong","sequence":"additional","affiliation":[{"name":"Hubei University of Chinese Medicine , , ,","place":["Wuhan, PR China, 430065"]},{"name":"Hubei Shizhen Laboratory , ,","place":["Wuhan, PR China, 430061"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2050-0921","authenticated-orcid":true,"given":"Da-Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Central China Normal University , , ,","place":["Wuhan, P.R. China, 430079"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4384-2593","authenticated-orcid":true,"given":"Guang-Fu","family":"Yang","sequence":"additional","affiliation":[{"name":"Central China Normal University , , ,","place":["Wuhan, P.R. China, 430079"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"issue":"3","key":"2026093009071408600_cit1","doi-asserted-by":"publisher","first-page":"425","DOI":"10.4161\/psb.19124","article-title":"Insights into the toxicity mechanism\nof and cell response to the herbicide 2,4-D in plants","volume":"7","author":"Pazmino","year":"2012","journal-title":"Plant. Signal. Behav."},{"issue":"2","key":"2026093009071408600_cit2","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1111\/jipb.12131","article-title":"Insight\ninto the mode of action of 2,4-dichlorophenoxyacetic acid (2,4-D)\nas an herbicide","volume":"56","author":"Song","year":"2014","journal-title":"J. Integr. Plant Biol."},{"key":"2026093009071408600_cit3","doi-asserted-by":"publisher","first-page":"975267","DOI":"10.3389\/fchem.2022.975267","article-title":"Design, synthesis,\nand herbicidal activity of indole-3-carboxylic acid derivatives as\npotential transport inhibitor response 1 antagonists","volume":"10","author":"Wang","year":"2022","journal-title":"Front. Chem."},{"issue":"1","key":"2026093009071408600_cit4","doi-asserted-by":"publisher","first-page":"3987","DOI":"10.1038\/s41467-022-31710-9","article-title":"Probing strigolactone\nperception mechanisms with rationally designed small-molecule agonists\nstimulating germination of root parasitic weeds","volume":"13","author":"Wang","year":"2022","journal-title":"Nat. Commun."},{"issue":"2","key":"2026093009071408600_cit5","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1111\/jipb.13225","article-title":"Auxin signaling: research\nadvances over the past 30 years","volume":"64","author":"Yu","year":"2022","journal-title":"J. Integr.\nPlant Biol."},{"issue":"6","key":"2026093009071408600_cit6","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1016\/j.cell.2009.03.001","article-title":"Auxin: a trigger for change in plant development","volume":"136","author":"Vanneste","year":"2009","journal-title":"Cell"},{"issue":"8060","key":"2026093009071408600_cit7","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1038\/s41586-025-08669-w","article-title":"TIR1-produced\ncAMP\nas a second messenger in transcriptional auxin signalling","volume":"640","author":"Chen","year":"2025","journal-title":"Nature"},{"issue":"3","key":"2026093009071408600_cit8","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.aac.2025.06.002","article-title":"cAMP: the true second\nmessenger in transcriptional\nauxin signaling","volume":"4","author":"Liu","year":"2025","journal-title":"Adv. Agrochem."},{"key":"2026093009071408600_cit9","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1038\/35104500","article-title":"Auxin regulates\nSCFTIR1-dependent degradation of AUXIAA proteins","volume":"414","author":"Gray","year":"2001","journal-title":"Nature"},{"key":"2026093009071408600_cit10","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.aac.2023.07.008","article-title":"Exploration and development\nof artificially synthesized plant growth regulators","volume":"3","author":"Yan","year":"2024","journal-title":"Adv. Agrochem."},{"issue":"7041","key":"2026093009071408600_cit11","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1038\/nature03542","article-title":"The Arabidopsis F-box protein TIR1\nis an auxin receptor","volume":"435","author":"Kepinski","year":"2005","journal-title":"Nature"},{"issue":"7041","key":"2026093009071408600_cit12","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1038\/nature03543","article-title":"The F-box protein TIR1 is an auxin\nreceptor","volume":"435","author":"Dharmasiri","year":"2005","journal-title":"Nature"},{"issue":"7136","key":"2026093009071408600_cit13","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1038\/nature05731","article-title":"Mechanism of auxin\nperception by the TIR1 ubiquitin ligase","volume":"446","author":"Tan","year":"2007","journal-title":"Nature"},{"issue":"2","key":"2026093009071408600_cit14","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1002\/ps.1860","article-title":"Auxin herbicides:\ncurrent status of mechanism and mode of action","volume":"66","author":"Grossmann","year":"2010","journal-title":"Pest Manage. Sci."},{"issue":"5","key":"2026093009071408600_cit15","doi-asserted-by":"publisher","first-page":"421","DOI":"10.4161\/psb.2.5.4417","article-title":"Auxin herbicide\naction: lifting the veil step by step","volume":"2","author":"Grossmann","year":"2007","journal-title":"Plant.\nSignal. Behav."},{"key":"2026093009071408600_cit16","doi-asserted-by":"publisher","first-page":"110631","DOI":"10.1016\/j.plantsci.2020.110631","article-title":"Synthetic auxin\nherbicides: finding the lock and key to weed resistance","volume":"300","author":"Todd","year":"2020","journal-title":"Plant Sci."},{"issue":"3","key":"2026093009071408600_cit17","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.bmc.2015.08.011","article-title":"The discovery of ArylexTM active and Rinskor TM active: Two novel auxin herbicides","volume":"24","author":"Epp","year":"2016","journal-title":"Bioorg. Med. Chem."},{"issue":"36","key":"2026093009071408600_cit18","doi-asserted-by":"publisher","first-page":"11075","DOI":"10.1021\/acs.jafc.1c07910","article-title":"A competitive\nedge: Competitor inspired scaffold hopping in herbicide lead optimization","volume":"70","author":"Barber","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"2026093009071408600_cit19","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1021\/bk-2015-1204.ch018","article-title":"Discovery and\nSAR of halauxifen methyl: A novel auxin herbicide.","volume-title":"Discovery And Synthesis Of Crop Protection Products","author":"Schmitzer","year":"2015"},{"key":"2026093009071408600_cit20","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.aac.2024.10.002","article-title":"Development of novel pyridine-based\nagrochemicals:\nA review","volume":"4","author":"Zakharychev","year":"2025","journal-title":"Adv. Agrochem"},{"issue":"4","key":"2026093009071408600_cit21","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1002\/ps.7294","article-title":"The differential\nbinding and biological efficacy of\nauxin herbicides","volume":"79","author":"Prusinska","year":"2023","journal-title":"Pest Manage. Sci."},{"key":"2026093009071408600_cit22","unstructured":"Jeremy, K.; Norbert, S. M.; Jeffrey, E. P.; Joshua, R.\n          4-Amino-6-(heterocyclic)picolinates\nand 6-amino-2-(heterocyclic)pyrimidine-4-carboxylates and their use\nas herbicides. WO 2018208582 A1, 2018."},{"issue":"5","key":"2026093009071408600_cit23","doi-asserted-by":"publisher","first-page":"2252","DOI":"10.1002\/ps.6250","article-title":"Design, synthesis and mode of action\nof novel 3-chloro-6-pyrazolyl\npicolinate derivatives as herbicide candidates","volume":"77","author":"Yang","year":"2021","journal-title":"Pest Manage. Sci."},{"issue":"3","key":"2026093009071408600_cit24","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.3390\/molecules28031431","article-title":"Design, synthesis,\nherbicidal activity, and structure-activity relationship study of\nnovel 6-(5-aryl-substituted-1-pyrazolyl)-2-picolinic acid as potential\nherbicides","volume":"28","author":"Feng","year":"2023","journal-title":"Molecules"},{"issue":"15","key":"2026093009071408600_cit25","doi-asserted-by":"publisher","first-page":"8840","DOI":"10.1021\/acs.jafc.3c08517","article-title":"Investigation into\nthe synthesis,\nbioactivity, and mechanism of action of the novel 6-pyrazolyl-2-picolinic\nacid as a herbicide","volume":"72","author":"Liu","year":"2024","journal-title":"J. Agric. Food Chem."},{"issue":"8","key":"2026093009071408600_cit26","doi-asserted-by":"publisher","first-page":"4555","DOI":"10.1021\/acs.jafc.4c08993","article-title":"Design, synthesis, and herbicidal\nevaluation of novel synthetic auxin herbicides containing 6-Indolylpyridine\noxime ester\/amine","volume":"73","author":"Zhang","year":"2025","journal-title":"J. Agric. Food Chem."},{"issue":"1","key":"2026093009071408600_cit27","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.aac.2022.09.002","article-title":"Strigolactone agonists\/antagonists for agricultural applications:\nNew opportunities","volume":"1","author":"Wang","year":"2022","journal-title":"Adv. Agrochem."},{"key":"2026093009071408600_cit28","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1111\/pbi.70369","article-title":"De Novo Design and\nSynthesis of Novel Benzoxazinone Derivatives Targeting Dihydroxyacid\nDehydratase","volume":"24","author":"He","year":"2025","journal-title":"Plant Biotechnol. J."},{"key":"2026093009071408600_cit29","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.33399","article-title":"Origin and evolution of the nuclear\nauxin response system","volume":"7","author":"Mutte","year":"2018","journal-title":"Elife"},{"key":"2026093009071408600_cit30","doi-asserted-by":"publisher","first-page":"5632","DOI":"10.1073\/pnas.0711146105","article-title":"Small-molecule agonists and antagonists of F-box protein\u2013substrate\ninteractions in auxin perception","volume":"105","author":"Hayashi","year":"2008","journal-title":"PNAS"},{"issue":"18","key":"2026093009071408600_cit31","doi-asserted-by":"publisher","first-page":"6478","DOI":"10.3390\/molecules28186478","article-title":"Application\nof quinoline ring in structural modification of natural products","volume":"28","author":"Zhao","year":"2023","journal-title":"Molecules"},{"issue":"22","key":"2026093009071408600_cit32","doi-asserted-by":"publisher","first-page":"12373","DOI":"10.1021\/acs.jafc.4c01582","article-title":"Quinoline derivatives in discovery\nand development\nof pesticides","volume":"72","author":"Cai","year":"2024","journal-title":"J. Agric. Food Chem."},{"issue":"41","key":"2026093009071408600_cit33","doi-asserted-by":"publisher","first-page":"11340","DOI":"10.1021\/acs.jafc.9b04224","article-title":"Design, synthesis, and antifungal evaluation of novel quinoline derivatives\ninspired from natural quinine alkaloids","volume":"67","author":"Yang","year":"2019","journal-title":"J.\nAgric. Food Chem."},{"key":"2026093009071408600_cit34","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.aac.2022.11.004","article-title":"Palladium-catalyzed\ncross-couplings\nin the synthesis of agrochemicals","volume":"1","author":"Zhu","year":"2022","journal-title":"Adv. Agrochem."},{"issue":"1","key":"2026093009071408600_cit35","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.tetlet.2009.10.089","article-title":"Electrophilic fluorination:\nthe aminopyridine dilemma","volume":"51","author":"Fields","year":"2010","journal-title":"Tetrahedron Lett."},{"key":"2026093009071408600_cit36","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1002\/(SICI)1526-4998(200005)56:5&lt;377::AID-PS154&gt;3.0.CO;2-M","article-title":"Role of auxinic herbicide-induced\nethylene on hypocotyl elongation and roothypocotyl radial expansion","volume":"56","author":"Wei","year":"2000","journal-title":"Pest Manage. Sci."},{"key":"2026093009071408600_cit37","doi-asserted-by":"publisher","first-page":"3225","DOI":"10.1021\/acs.jafc.2c09082","article-title":"Design, synthesis,\nand metabolism studies of N-1,4-diketophenyltriazinones\nas protoporphyrinogen IX oxidase inhibitors","volume":"71","author":"Liu","year":"2023","journal-title":"J. Agric. Food Chem."},{"issue":"2","key":"2026093009071408600_cit38","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1021\/acs.jafc.4c08544","article-title":"Discovery\nof Triketone\u2013Indazolones\nas Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibiting-Based Herbicides","volume":"73","author":"Chen","year":"2025","journal-title":"J. Agric. Food Chem."},{"issue":"15","key":"2026093009071408600_cit39","doi-asserted-by":"publisher","first-page":"8095","DOI":"10.3390\/ijerph18158095","article-title":"Mutagenicity assessment\nto pesticide adjuvants of toluene, chloroform, and trichloroethylene\nby ames test","volume":"18","author":"Zhang","year":"2021","journal-title":"Int. J. Environ. Res. Public Health"},{"issue":"37","key":"2026093009071408600_cit40","doi-asserted-by":"publisher","first-page":"10489","DOI":"10.1021\/acs.jafc.9b03109","article-title":"Design and Synthesis of novel 4-hydroxyl-3-(2-phenoxyacetyl)-pyran-2-one\nderivatives for use as herbicides and evaluation of their mode of\naction","volume":"67","author":"Lei","year":"2019","journal-title":"J. Agric. Food Chem."}],"container-title":["Journal of Agricultural\nand Food Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jafc.6c01648","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/38\/29898\/68570177\/acs.jafc.6c01648.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/38\/29898\/68570177\/acs.jafc.6c01648.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:20:44Z","timestamp":1790774444000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jafcau\/article\/74\/38\/29898\/5433672\/Pocket-Oriented-Design-of-Benzene-Fused"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":40,"journal-issue":{"issue":"38","published-online":{"date-parts":[[2026,9,21]]},"published-print":{"date-parts":[[2026,9,30]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jafc.6c01648","relation":{},"ISSN":["0021-8561","1520-5118"],"issn-type":[{"value":"0021-8561","type":"print"},{"value":"1520-5118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]}}}