{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:18:18Z","timestamp":1788254298231,"version":"build-2803163510"},"reference-count":45,"publisher":"American Chemical Society (ACS)","issue":"33","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32560668"],"award-info":[{"award-number":["32560668"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018533","name":"Major Scientific and Technological Special Project of Guizhou Province","doi-asserted-by":"publisher","award":["Qiankehechengguo [2024]zhongda007"],"award-info":[{"award-number":["Qiankehechengguo [2024]zhongda007"]}],"id":[{"id":"10.13039\/501100018533","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Scientific and Technological Innovation Platform Research Project of Guizhou Province","doi-asserted-by":"publisher","award":["CXPTXM [2025] 022"],"award-info":[{"award-number":["CXPTXM [2025] 022"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Guizhou Provincial Foundation for Excellent Scholars Program","doi-asserted-by":"publisher","award":["GCC[2023]069"],"award-info":[{"award-number":["GCC[2023]069"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Central Government Guides Local Science and Technology Development Fund Projects","doi-asserted-by":"publisher","award":["Qiankehezhongyindi [2024]007"],"award-info":[{"award-number":["Qiankehezhongyindi [2024]007"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The use of herbicides represents one of the effective weed management strategies. To create high-efficiency, low-risk protoporphyrinogen IX oxidase (PPO)-targeted herbicides, a set of novel N-phenylphthalimides bearing 1,3,4-oxadiazole and acylhydrazide fragments was designed and synthesized. Bioassays revealed that most of the compounds possessed potent herbicidal activity against six common weeds. Compound A9 exerted good inhibitory effects on Nicotiana tabacum PPO (NtPPO) with a Ki of 14.0 nM, outperforming commercial flumioxazin (46.3 nM) and flumiclorac-pentyl (52.0 nM). Molecular docking validated that A9 binds tightly to NtPPO via hydrogen bonds with Arg98 (2.8 \u00c5), \u03c0\u2013\u03c0 stacking with Phe392, and \u03c0\u2013alkyl sandwich interactions with Leu356\/Leu372. Assays with PPO-deficient and PPO-complemented Escherichia coli strains, alongside AtPPO-overexpressing and mutant Arabidopsis, collectively verified A9 functions as a target-specific PPO inhibitor.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c02325","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T13:01:57Z","timestamp":1786626117000},"page":"25923-25934","source":"Crossref","is-referenced-by-count":0,"title":["Novel\n                    <i>N<\/i>\n                    -Phenylphthalimide\nDerivatives as Protoporphyrinogen IX Oxidase-Targeted Inhibitor Herbicides"],"prefix":"10.1021","volume":"74","author":[{"given":"Wang","family":"Geng","sequence":"first","affiliation":[{"name":"Center for R&D of Fine Chemicals of Guizhou University , , ,","place":["Guiyang, P. R. China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Center for R&D of Fine Chemicals of Guizhou University , , ,","place":["Guiyang, P. R. China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for R&D of Fine Chemicals of Guizhou University , , ,","place":["Guiyang, P. R. China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsong","family":"Yang","sequence":"additional","affiliation":[{"name":"Center for R&D of Fine Chemicals of Guizhou University , , ,","place":["Guiyang, P. R. China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Yan","sequence":"additional","affiliation":[{"name":"Liupanshui Normal University , , ,","place":["Liupanshui, P. R. China, 553004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4070-0824","authenticated-orcid":true,"given":"Xiuhai","family":"Gan","sequence":"additional","affiliation":[{"name":"Center for R&D of Fine Chemicals of Guizhou University , , ,","place":["Guiyang, P. R. China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"2026090104480810400_cit1","doi-asserted-by":"publisher","DOI":"10.3389\/fpls.2022.1034649","article-title":"Allelopathy and its application as\na weed management tool: A review","volume":"13","author":"Khamare","year":"2022","journal-title":"Front. Plant\nSci."},{"key":"2026090104480810400_cit2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xplc.2024.100816","article-title":"Weed biology\nand management in the\nmulti-omics era: Progress and perspectives","volume":"5","author":"Chen","year":"2024","journal-title":"Plant Commun."},{"key":"2026090104480810400_cit3","doi-asserted-by":"publisher","first-page":"5791","DOI":"10.1002\/ps.8310","article-title":"Cytochrome P450 CYP81A104\nin Eleusine indica confers resistance to\nmultiherbicide with different modes of action","volume":"80","author":"Yao","year":"2024","journal-title":"Pest Manage. Sci."},{"key":"2026090104480810400_cit4","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1002\/ps.3863","article-title":"Perspectives\non transgenic, herbicide-resistant crops in the United States almost\n20 years after introduction","volume":"71","author":"Duke","year":"2015","journal-title":"Pest Manage. Sci."},{"key":"2026090104480810400_cit5","doi-asserted-by":"publisher","first-page":"3036","DOI":"10.1002\/ps.6457","article-title":"Can new herbicide\ndiscovery allow\nweed management to outpace resistance evolution?","volume":"77","author":"Gaines","year":"2021","journal-title":"Pest Manage. Sci."},{"key":"2026090104480810400_cit6","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/s41893-019-0450-8","article-title":"The costs of human-induced evolution\nin an agricultural system","volume":"3","author":"Varah","year":"2020","journal-title":"Nat. Sustainability"},{"key":"2026090104480810400_cit7","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1042\/BJ20061321","article-title":"Functional\ndefinition of the tobacco\nprotoporphyrinogen IX oxidase substrate-binding site","volume":"402","author":"Heinemann","year":"2007","journal-title":"Biochem. J."},{"key":"2026090104480810400_cit8","doi-asserted-by":"publisher","first-page":"9254","DOI":"10.1021\/acs.jafc.9b02996","article-title":"Design,\nherbicidal activity, and QSAR analysis of cycloalka[d]quinazoline-2,4-dione-benzoxazinones as protoporphyrinogen\nIX oxidase inhibitors","volume":"67","author":"Wang","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"2026090104480810400_cit9","doi-asserted-by":"publisher","first-page":"13672","DOI":"10.1021\/acs.jafc.0c05955","article-title":"Design, synthesis, and\nmolecular mechanism\nstudies of N-phenylisoxazoline-thiadiazolo[3,4-a]pyridazine hybrids as protoporphyrinogen IX oxidase inhibitors","volume":"68","author":"Zhang","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"2026090104480810400_cit10","doi-asserted-by":"publisher","first-page":"14115","DOI":"10.1021\/acs.jafc.1c05665","article-title":"Discovery of a potent\nthieno[2,3-d]pyrimidine-2,4-dione-based protoporphyrinogen\nIX oxidase inhibitor through an in silico structure-guided\noptimization approach","volume":"69","author":"Wang","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"2026090104480810400_cit11","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1002\/ps.2780400404","article-title":"Enantioselectivity\nof protoporphyrinogen oxidase-inhibiting\nherbicides","volume":"40","author":"Nandihalli","year":"1994","journal-title":"Pestic. Sci."},{"key":"2026090104480810400_cit12","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.pestbp.2018.08.010","article-title":"Biochemical and physiological mode\nof action of tiafenacil, a new protoporphyrinogen IX oxidase-inhibiting\nherbicide","volume":"152","author":"Park","year":"2018","journal-title":"Pestic. Biochem. Physiol."},{"key":"2026090104480810400_cit13","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1002\/ps.3728","article-title":"Evolution\nof resistance to phytoene desaturase and protoporphyrinogen oxidase\ninhibitors-state of knowledge","volume":"70","author":"Dayan","year":"2014","journal-title":"Pest Manage.\nSci."},{"key":"2026090104480810400_cit14","doi-asserted-by":"publisher","DOI":"10.1016\/j.pestbp.2020.104684","article-title":"Novel phenoxy-(trifluoromethyl)\npyridine-2-pyrrolidinone-based inhibitors\nof protoporphyrinogen IX oxidase: Design, synthesis, and herbicidal\nactivity","volume":"170","author":"Zhao","year":"2020","journal-title":"Pestic. Biochem. Physiol."},{"key":"2026090104480810400_cit15","doi-asserted-by":"publisher","first-page":"7948","DOI":"10.1016\/j.bmc.2010.09.036","article-title":"Design,\nsyntheses and 3D-QSAR studies of novel N-phenyl pyrrolidin-2-ones\nand N-phenyl-1H-pyrrol-2-ones as\nprotoporphyrinogen IX oxidase inhibitors","volume":"18","author":"Zhang","year":"2010","journal-title":"Bioorg.\nMed. Chem."},{"key":"2026090104480810400_cit16","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.ab.2008.09.023","article-title":"A capillary electrophoresis assay\nfor recombinant Bacillus subtilis protoporphyrinogen\noxidase","volume":"383","author":"Tan","year":"2008","journal-title":"Anal. Biochem."},{"key":"2026090104480810400_cit17","doi-asserted-by":"publisher","first-page":"10850","DOI":"10.1021\/acs.jafc.5c14456","article-title":"Design,\nsynthesis and biological evaluation of N-phenylphthalimide\nprotoporphyrinogen IX oxidase inhibitor herbicides","volume":"74","author":"Geng","year":"2026","journal-title":"J. Agric. Food Chem."},{"key":"2026090104480810400_cit18","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1039\/c2md20199b","article-title":"Diaryl ether\nderivatives\nas anticancer agents\u2013a review","volume":"3","author":"Bedos-Belval","year":"2012","journal-title":"Med. Chem.\nCommun."},{"key":"2026090104480810400_cit19","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1002\/ejoc.201001520","article-title":"Diaryl\nether formation in the synthesis\nof natural products","volume":"2011","author":"Pitsinos","year":"2011","journal-title":"Eur. J. Org. Chem."},{"key":"2026090104480810400_cit20","doi-asserted-by":"publisher","first-page":"17191","DOI":"10.1021\/acs.jafc.4c01389","article-title":"Design,\nsynthesis, and herbicidal activity of novel tetrahydrophthalimide\nderivatives containing oxadiazole\/thiadiazole moieties","volume":"72","author":"Geng","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"2026090104480810400_cit21","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/0048-3575(91)90107-W","article-title":"In vitro mode of action of N-phenylimide photobleaching\nherbicides","volume":"40","author":"Mito","year":"1991","journal-title":"Pestic. Biochem. Physiol."},{"key":"2026090104480810400_cit22","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202409516","article-title":"Ethyl\nlactate ameliorates hepatic steatosis and acute-on-chronic\nliver injury in alcohol-associated liver disease by inducing fibroblast\ngrowth factor 21","author":"Jiang","year":"2024","journal-title":"Adv. Sci."},{"key":"2026090104480810400_cit23","doi-asserted-by":"publisher","first-page":"23097","DOI":"10.1021\/acs.jafc.4c01824","article-title":"Design, synthesis, and herbicidal activities of N-(5-(3,5-methoxyphenyl)-(thiazole-2-yl))phenoxyacetamide\nderivatives","volume":"72","author":"Liu","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"2026090104480810400_cit24","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.bmc.2014.11.016","article-title":"Synthesis\nand biological evaluation of phenoxyacetic\nacid derivatives as novel free fatty acid receptor 1 agonists","volume":"23","author":"Wang","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"2026090104480810400_cit25","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2020.115959","article-title":"Design and synthesis\nof acrylate\nand acrylamide substituted pyrimidinediones as potential PPO herbicides","volume":"31","author":"Lee","year":"2021","journal-title":"Bioorg. Med. Chem."},{"key":"2026090104480810400_cit26","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24234363","article-title":"Design and synthesis\nof N-phenyl phthalimides as potent protoporphyrinogen\noxidase inhibitors","volume":"24","author":"Gao","year":"2019","journal-title":"Molecules"},{"key":"2026090104480810400_cit27","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.pestbp.2017.04.007","article-title":"Tetrahydrophthalimidobenzoates\nas protoporphyrinogen IX oxidase inhibiting herbicides","volume":"139","author":"Chen","year":"2017","journal-title":"Pestic. Biochem. Physiol."},{"key":"2026090104480810400_cit28","doi-asserted-by":"publisher","first-page":"12382","DOI":"10.1021\/acs.jafc.9b04844","article-title":"Discovery\nof novel N-isoxazolinylphenyltriazinones as promising\nprotoporphyrinogen IX oxidase inhibitors","volume":"67","author":"Wang","year":"2019","journal-title":"J.\nAgric. Food Chem."},{"key":"2026090104480810400_cit29","doi-asserted-by":"publisher","first-page":"8746","DOI":"10.1021\/acs.jafc.3c00168","article-title":"Discovery of a subnanomolar inhibitor\nof protoporphyrinogen IX oxidase via fragment-based virtual screening","volume":"71","author":"Zheng","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"2026090104480810400_cit30","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.jsb.2009.11.012","article-title":"Structural\ninsight into unique properties of protoporphyrinogen oxidase from\nBacillus subtilis","volume":"170","author":"Qin","year":"2010","journal-title":"J. Struct. Biol."},{"key":"2026090104480810400_cit31","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1017\/S0043174500073239","article-title":"Protoporphyrinogen\noxidase-inhibiting herbicides","volume":"39","author":"Duke","year":"1991","journal-title":"Weed Sci."},{"key":"2026090104480810400_cit32","doi-asserted-by":"publisher","first-page":"4081","DOI":"10.1021\/acs.jafc.1c00796","article-title":"Discovery of N-phenylaminomethylthioacetylpyrimidine-2,4-diones\nas protoporphyrinogen IX oxidase inhibitors through a reaction intermediate\nderivation approach","volume":"69","author":"Wang","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"2026090104480810400_cit33","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2021.116165","article-title":"Design, synthesis,\nand molecular simulation studies of N-phenyltetrahydroquinazolinones\nas protoporphyrinogen IX oxidase\ninhibitors","volume":"39","author":"Liang","year":"2021","journal-title":"Bioorg. Med. Chem."},{"key":"2026090104480810400_cit34","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1002\/ps.3894","article-title":"Design, synthesis\nand herbicidal activity of novel quinazoline-2,4-diones as 4-hydroxyphenylpyruvate\ndioxygenase inhibitors","volume":"71","author":"Wang","year":"2015","journal-title":"Pest Manage. Sci."},{"key":"2026090104480810400_cit35","doi-asserted-by":"publisher","first-page":"5625","DOI":"10.1021\/acs.jafc.3c07411","article-title":"Design, synthesis, and biological\nactivity of novel phenyltriazolinone PPO inhibitors containing five-membered\nheterocycles","volume":"72","author":"Zhao","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"2026090104480810400_cit36","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1021\/acs.jafc.1c05210","article-title":"Design, synthesis,\nand herbicidal activity of diphenyl\nether derivatives containing a five-membered heterocycle","volume":"70","author":"Zhao","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"2026090104480810400_cit37","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1002\/ps.70331","article-title":"Inhibitory effect of volatiles produced by Bacillus\nsafensis TR-47 on Aspergillus flavus and aflatoxins in the peanuts\nduring storage","volume":"82","author":"Gong","year":"2026","journal-title":"Pest Manage. Sci."},{"key":"2026090104480810400_cit38","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1007\/s11103-019-00925-8","article-title":"Characterization\nof HemY-type protoporphyrinogen IX oxidase genes from cyanobacteria\nand their functioning in transgenic Arabidopsis","volume":"101","author":"Yoon","year":"2019","journal-title":"Plant Mol. Biol."},{"key":"2026090104480810400_cit39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/dnares\/2.1.1","article-title":"Cloning and identification\nof the\nhemG gene encoding protoporphyrinogen oxidase (PPO) of Escherichia coli K-12","volume":"2","author":"Nishimura","year":"1995","journal-title":"DNA\nRes."},{"key":"2026090104480810400_cit40","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1093\/plphys\/kiae062","article-title":"Dual plastid targeting\nof protoporphyrinogen\noxidase 2 in Amaranthaceae promotes herbicide tolerance","volume":"195","author":"Wittmann","year":"2024","journal-title":"Plant Physiol."},{"key":"2026090104480810400_cit41","doi-asserted-by":"publisher","first-page":"10772","DOI":"10.1021\/acs.jafc.3c09157","article-title":"Design,\nsynthesis, and biological evaluation of pyridazinone containing derivatives\nas novel protoporphyrinogen IX oxidase inhibitors","volume":"72","author":"Zhang","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"2026090104480810400_cit42","doi-asserted-by":"publisher","first-page":"27075","DOI":"10.1021\/acs.jafc.4c07227","article-title":"Design,\nsynthesis, and assessment of fungicidal activity of active substructure\n1,2,4-triazole containing coumarin","volume":"72","author":"Lv","year":"2024","journal-title":"J. Agric.\nFood Chem."},{"key":"2026090104480810400_cit43","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1007\/978-1-0716-3441-7_11","article-title":"Accelerating molecular dynamics simulations for drug discovery","volume":"2714","author":"Koirala","year":"2024","journal-title":"Methods Mol. Biol."},{"key":"2026090104480810400_cit44","doi-asserted-by":"publisher","first-page":"8139","DOI":"10.1021\/acs.jpcb.3c04142","article-title":"Free energy landscapes of the tautomeric\ninterconversion\nof pyridoxal 5\u2032-phosphate aldimines at the active site of ornithine\ndecarboxylase in aqueous media","volume":"127","author":"Rastogi","year":"2023","journal-title":"J. Phys. Chem.\nB"},{"key":"2026090104480810400_cit45","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1104\/pp.124.1.59","article-title":"Molecular characterization and subcellular\nlocalization of protoporphyrinogen oxidase in spinach chloroplasts","volume":"124","author":"Che","year":"2000","journal-title":"Plant Physiol."}],"container-title":["Journal of Agricultural\nand Food Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jafc.6c02325","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/33\/25923\/66523270\/acs.jafc.6c02325.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/33\/25923\/66523270\/acs.jafc.6c02325.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T08:48:15Z","timestamp":1788252495000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jafcau\/article\/74\/33\/25923\/5254173\/Novel-N-Phenylphthalimide-Derivatives-as"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,13]]},"references-count":45,"journal-issue":{"issue":"33","published-online":{"date-parts":[[2026,8,13]]},"published-print":{"date-parts":[[2026,8,26]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jafc.6c02325","relation":{},"ISSN":["0021-8561","1520-5118"],"issn-type":[{"value":"0021-8561","type":"print"},{"value":"1520-5118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,13]]}}}