{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:02:14Z","timestamp":1790776934338,"version":"4.1.0"},"reference-count":37,"publisher":"American Chemical Society (ACS)","issue":"38","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100005145","name":"Basic Research Program of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20251515"],"award-info":[{"award-number":["BK20251515"]}],"id":[{"id":"10.13039\/501100005145","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["ZJ26195005"],"award-info":[{"award-number":["ZJ26195005"]}],"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>Plant pathogenic fungi pose a significant threat to global crop productivity and food security. Herein, we report the design and synthesis of 55 coumarin\u2013oxazole, \u2212isoxazole, and \u2212pyrazole hybrids as novel antifungal agents. Most derivatives exhibited notable potency, with C1, C4, and C5 showing strong activity against Rhizoctonia solani (EC50 = 6.4, 5.9, and 8.6 \u03bcg\/mL), while C2 displayed superior activity against Alternaria solani (EC50 = 4.5 \u03bcg\/mL). Structure\u2013activity relationship and density functional theory (DFT) analyses revealed that the pyrazole heterocycle and electron-withdrawing substituents were key determinants of potency. Mechanistic studies on C4 demonstrated that it induces morphological damage, mitochondrial dysfunction (reactive oxygen species (ROS) overproduction, mitochondrial membrane potential (MMP) dissipation), cell membrane disruption (propidium iodide (PI) fluorescence, nucleic acid leakage, malondialdehyde (MDA) elevation, increased conductivity), and interferes with ergosterol-associated pathways. These findings establish coumarin\u2013azole hybrids as promising leads for antifungal development.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c10905","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T08:01:18Z","timestamp":1789718478000},"page":"30090-30101","source":"Crossref","is-referenced-by-count":0,"title":["Novel Coumarin\nDerivatives Containing Oxazole\/Isoxazole\/Pyrazole\nGroups as Antifungal Agents: Design, Synthesis, Quantitative Structure\u2013Activity\nRelationships, and Preliminary Mechanistic Insights"],"prefix":"10.1021","volume":"74","author":[{"given":"Peng","family":"Dai","sequence":"first","affiliation":[{"name":"Anqing Normal University , , ,","place":["Anqing, China, 261433"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Hong","sequence":"additional","affiliation":[{"name":"Anqing Normal University , , ,","place":["Anqing, China, 261433"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Chengdu, China, 610213"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weipeng","family":"Sun","sequence":"additional","affiliation":[{"name":"Anqing Normal University , , ,","place":["Anqing, China, 261433"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keke","family":"Liu","sequence":"additional","affiliation":[{"name":"Hainan University , , ,","place":["Haikou, China, 570228"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyu","family":"Liang","sequence":"additional","affiliation":[{"name":"Anqing Normal University , , ,","place":["Anqing, China, 261433"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2395-7635","authenticated-orcid":true,"given":"Chunyin","family":"Ye","sequence":"additional","affiliation":[{"name":"Anqing Normal University , , ,","place":["Anqing, China, 261433"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Anqing Normal University , , ,","place":["Anqing, China, 261433"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghan","family":"Qin","sequence":"additional","affiliation":[{"name":"Xinghuo Industrial Park, High-tech Industrial Development Zone , Yijiang District, , ,","place":["Wuhu, Anhui, China, 241002"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1994-5306","authenticated-orcid":true,"given":"Weihua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Nanjing Agricultural University , , ,","place":["Nanjing, China, 210095"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"2026093009081906900_cit1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-443-13993-2.00001-3","article-title":"Exponential population growth\nand global food security: challenges and alternatives","volume-title":"Bioremediation of Emerging Contaminants from Soils","author":"Ghosh","year":"2024"},{"key":"2026093009081906900_cit2","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1057\/s41599-025-05315-8","article-title":"Exploring the reality of global food\ninsecurity and policy gaps","volume":"12","author":"Mumah","year":"2025","journal-title":"Humanit. Soc. Sci.\nCommun."},{"key":"2026093009081906900_cit3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jafr.2023.100827","article-title":"Selected emerging\nand reemerging plant pathogens affecting the food basket: A threat\nto food security","volume":"14","author":"Mwangi","year":"2023","journal-title":"J. Agric. Food Res."},{"key":"2026093009081906900_cit4","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1038\/s41559-018-0793-y","article-title":"The global burden of pathogens and pests on major food\ncrops","volume":"3","author":"Savary","year":"2019","journal-title":"Nat. Ecol. Evol."},{"key":"2026093009081906900_cit5","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/B978-0-12-821035-2.00005-X","article-title":"Research and development\nof green\npesticides in China","volume-title":"Recent Highlights\nin the Discovery and Optimization of Crop Protection Products","author":"Shao","year":"2021"},{"key":"2026093009081906900_cit6","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1002\/ps.8563","article-title":"Design and synthesis\nof camphor-thiazole derivatives as potent antifungal agents: structure\u2013activity\nrelationship and preliminary mechanistic study","volume":"81","author":"Dai","year":"2025","journal-title":"Pest Manag. Sci."},{"key":"2026093009081906900_cit7","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1002\/ps.8481","article-title":"Rational design and discovery of\nnovel hydrazide derivatives as potent succinate dehydrogenase inhibitors\ninspired by natural D\/L-camphor","volume":"81","author":"Dai","year":"2025","journal-title":"Pest Manag.\nSci."},{"key":"2026093009081906900_cit8","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.aac.2024.11.007","article-title":"Discovery of novel\nD\/L-camphor derivatives containing oxime ester as fungicide candidates:\nantifungal activity, structure\u2013activity relationship and preliminary\nmechanistic study","volume":"4","author":"Dai","year":"2025","journal-title":"Adv. Agrochem."},{"key":"2026093009081906900_cit9","doi-asserted-by":"publisher","first-page":"11938","DOI":"10.1021\/acs.jafc.4c00200","article-title":"3D-QSAR-directed synthesis\nof halogenated coumarin-3-hydrazide derivatives: unveiling their potential\nas SDHI antifungal agents","volume":"72","author":"Dai","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"2026093009081906900_cit10","doi-asserted-by":"publisher","first-page":"5983","DOI":"10.1021\/acs.jafc.3c06032","article-title":"Design, synthesis,\nantifungal activity, and 3D-QSAR\nof novel oxime ether-containing coumarin derivatives as potential\nfungicides","volume":"72","author":"Dai","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"2026093009081906900_cit11","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2025.144655","article-title":"Discovery of novel\n3-phenylhydrazone coumarin derivatives as potential antifungal agents\nagainst phytopathogenic fungi","volume":"486","author":"Li","year":"2025","journal-title":"Food Chem."},{"key":"2026093009081906900_cit12","doi-asserted-by":"publisher","DOI":"10.2478\/acph-2023-0024","article-title":"Xanthoxyletin\nblocks the RANK\/RANKL\nsignaling pathway to suppress the growth of human pancreatic cancer\ncells","volume":"73","author":"Zhang","year":"2023","journal-title":"Croat. Pharm. Soc."},{"key":"2026093009081906900_cit13","doi-asserted-by":"publisher","first-page":"588","DOI":"10.3390\/biology14060588","article-title":"Osthole: A coumarin with dual roles\nin biology and chemistry","volume":"14","author":"Lv","year":"2025","journal-title":"Biology"},{"key":"2026093009081906900_cit14","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2021.130605","article-title":"Structural elucidation\nof flavonoids from Shatianyu (Citrus grandis L. Osbeck) pulp and screening\nof key antioxidant components","volume":"366","author":"Deng","year":"2022","journal-title":"Food Chem."},{"key":"2026093009081906900_cit15","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.ejmech.2016.03.069","article-title":"Microwave-assisted\nsynthesis and antifungal activity\nof novel coumarin derivatives: pyrano[3,2-c]chromene-2,5-diones","volume":"116","author":"Zhang","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"2026093009081906900_cit16","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.ejmech.2017.06.044","article-title":"New arylpyrazoline-coumarins:\nsynthesis and anti-inflammatory activity","volume":"138","author":"Chen","year":"2017","journal-title":"Eur.\nJ. Med. Chem."},{"key":"2026093009081906900_cit17","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1016\/j.ejmech.2015.07.010","article-title":"Coumarins as anticancer\nagents: a\nreview on synthetic strategies, mechanism of action and SAR studies","volume":"101","author":"Thakur","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"2026093009081906900_cit18","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.ejmech.2016.07.056","article-title":"Therapeutic\npotential\nof coumarins as antiviral agents","volume":"123","author":"Hassan","year":"2016","journal-title":"Eur. J. Med.\nChem."},{"key":"2026093009081906900_cit19","doi-asserted-by":"publisher","first-page":"956","DOI":"10.2174\/0115734064361520250115090651","article-title":"Recent advancements in the synthetic chemistry of oxazole derivatives\nand their significant medicinal applications","volume":"21","author":"Yadav","year":"2025","journal-title":"Med. Chem."},{"key":"2026093009081906900_cit20","doi-asserted-by":"publisher","first-page":"3000","DOI":"10.1021\/jacsau.5c00326","article-title":"Discovery and characterization\nof oxazolismycin, an oxazole-containing natural product with an atypical\nloading mechanism","volume":"5","author":"Pan","year":"2025","journal-title":"JACS Au"},{"key":"2026093009081906900_cit21","doi-asserted-by":"publisher","first-page":"228","DOI":"10.3390\/ph16020228","article-title":"Isoxazole\/isoxazoline skeleton in\nthe structural modification of natural products: a review","volume":"16","author":"Wang","year":"2023","journal-title":"Pharmaceuticals"},{"key":"2026093009081906900_cit22","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2024.116898","article-title":"Isoxazole compounds:\nunveiling the synthetic strategy, in-silico\nSAR and toxicity studies and future perspective as PARP inhibitor\nin cancer therapy","volume":"279","author":"Malik","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"2026093009081906900_cit23","doi-asserted-by":"publisher","DOI":"10.1016\/j.arabjc.2024.105794","article-title":"Natural products\u2013isoxazole\nhybrids: a review of developments in medicinal chemistry","volume":"17","author":"Wang","year":"2024","journal-title":"Arab. J. Chem."},{"key":"2026093009081906900_cit24","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1016\/j.ejmech.2013.08.053","article-title":"Pyrazole-containing\nnatural products: synthetic preview and biological significance","volume":"69","author":"Kumar","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"2026093009081906900_cit25","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/B978-0-12-821035-2.00013-9","article-title":"Discovery of oxazosulfyl: a\nnovel broad-spectrum insecticide","volume-title":"Recent\nHighlights in the Discovery and Optimization of Crop Protection Products","author":"Ito","year":"2021"},{"key":"2026093009081906900_cit26","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1002\/1526-4998(200102)57:2&lt;133::AID-PS276&gt;3.0.CO;2-0","article-title":"Isoxaflutole: the background to its\ndiscovery and the basis of its herbicidal properties","volume":"57","author":"Pallett","year":"2001","journal-title":"Pest Manag. Sci."},{"key":"2026093009081906900_cit27","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1080\/03601234.2018.1473974","article-title":"The control effect\nof fungicide pyraclostrobin against freckle disease\nof banana and its residue dynamics under field conditions","volume":"53","author":"Yang","year":"2018","journal-title":"J. Environ. Sci. Health B"},{"key":"2026093009081906900_cit28","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1007\/s42161-023-01466-2","article-title":"Impact of pyraclostrobin\non the growth of Fusarium pseudograminearum and its\ncontrol efficacy against wheat crown rot","volume":"105","author":"Hou","year":"2023","journal-title":"J.\nPlant Pathol."},{"key":"2026093009081906900_cit29","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3390\/molecules30020394","article-title":"Synthesis and evaluation of biologically\nactive compounds\nfrom heterocycles class","volume":"30","author":"Barbuceanu","year":"2025","journal-title":"Molecules"},{"key":"2026093009081906900_cit30","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1016\/j.aac.2023.09.004","article-title":"Recent\nadvances in the natural products-based lead discovery for new agrochemicals","volume":"2","author":"Zhang","year":"2023","journal-title":"Adv. Agrochem."},{"key":"2026093009081906900_cit31","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1584\/jpestics.D17-075","article-title":"Design, synthesis, antifungal activity, and 3D-QSAR of coumarin derivatives","volume":"43","author":"Wei","year":"2018","journal-title":"J. Pestic. Sci."},{"key":"2026093009081906900_cit32","doi-asserted-by":"publisher","DOI":"10.1016\/j.arabjc.2020.10.027","article-title":"The synthesis of coumarin\nthiazoles containing a trifluoromethyl\ngroup and their antifungal activities","volume":"14","author":"Yang","year":"2021","journal-title":"Arab.\nJ. Chem."},{"key":"2026093009081906900_cit33","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1002\/jhet.3391","article-title":"Design, synthesis, and antifungal\nactivity of 3-(thiophen-2-yl)-1,5-dihydro-2H-pyrrol-2-one derivatives\nbearing a carbonic ester group","volume":"56","author":"Wang","year":"2019","journal-title":"J. Heterocycl.\nChem."},{"key":"2026093009081906900_cit34","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s13065-018-0452-z","article-title":"Design and\nsynthesis of novel 3-(thiophen-2-yl)-1,5-dihydro-2H-pyrrol-2-one\nderivatives bearing a hydrazone moiety as potential fungicides","volume":"12","author":"Wang","year":"2018","journal-title":"Chem. Cent. J."},{"key":"2026093009081906900_cit35","doi-asserted-by":"publisher","first-page":"20071","DOI":"10.1039\/D0NJ04551A","article-title":"Novel pyrrolidine-2,4-dione\nderivatives\ncontaining pharmacophores of both hydrazine and diphenyl ether as\npotential antifungal agents: design, synthesis, biological evaluation,\nand 3D-QSAR study","volume":"44","author":"Hu","year":"2020","journal-title":"New J. Chem."},{"key":"2026093009081906900_cit36","doi-asserted-by":"publisher","first-page":"6231","DOI":"10.1021\/acs.jafc.4c09156","article-title":"Discovery of novel\npyrazole\/thiazole derivatives containing cyano\/thiocyanato groups\nas fungicide candidates","volume":"73","author":"Dai","year":"2025","journal-title":"J. Agric. Food Chem."},{"key":"2026093009081906900_cit37","doi-asserted-by":"publisher","first-page":"21419","DOI":"10.1021\/acs.jafc.4c03505","article-title":"Design, synthesis,\nantifungal evaluation, and three-dimensional quantitative structure\u2013activity\nrelationship of novel 5-sulfonyl-1,3,4-thiadiazole flavonoids","volume":"72","author":"Dai","year":"2024","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.6c10905","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/38\/30090\/68551405\/acs.jafc.6c10905.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/38\/30090\/68551405\/acs.jafc.6c10905.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:49:56Z","timestamp":1790776196000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jafcau\/article\/74\/38\/30090\/5432446\/Novel-Coumarin-Derivatives-Containing-Oxazole"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,18]]},"references-count":37,"journal-issue":{"issue":"38","published-online":{"date-parts":[[2026,9,18]]},"published-print":{"date-parts":[[2026,9,30]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jafc.6c10905","relation":{},"ISSN":["0021-8561","1520-5118"],"issn-type":[{"value":"0021-8561","type":"print"},{"value":"1520-5118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,18]]}}}