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Structural optimization of natural products offers a viable route to novel SDHI skeletons. Herein, a series of coumarin hydrazone derivatives were designed and synthesized by a scaffold splicing strategy. Compound 3p showed 100% antifungal activity against Rhizoctonia solani at 50 \u03bcg\/mL, with an EC50 of 1.16 \u03bcg\/mL. On rice leaves, 3p achieved 98.4% preventive efficacy against R. solani, outperforming Boscalid (69.6%) at the same concentration. Furthermore, it caused hyphal distortion and mitochondrial damage, similar to boscalid. Enzymatic assays confirmed 3p as an SDHI with an IC50 of 8.69 \u03bcM, and molecular docking indicated stable binding within the SDH active site. ATP analysis revealed intracellular levels were reduced to 72% in 3p-treated mycelia compared to controls. Therefore, compound 3p is a promising leader for developing novel SDH inhibitors.<\/jats:p>","DOI":"10.1021\/acs.jafc.5c14526","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T04:17:59Z","timestamp":1784261879000},"page":"22497-22506","source":"Crossref","is-referenced-by-count":1,"title":["Coumarin Hydrazone\nDerivatives as Potent Succinate\nDehydrogenase Inhibitors and Effective Antifungal Agents against\n                    <i>Rhizoctonia solani<\/i>"],"prefix":"10.1021","volume":"74","author":[{"given":"Wang","family":"Chen","sequence":"first","affiliation":[{"name":"Nanjing Agricultural University , , ,","place":["Nanjing, PR China, 210095"]},{"name":"Ministry of Education , , ,","place":["Nanjing, PR China, 210095"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixiang","family":"Fu","sequence":"additional","affiliation":[{"name":"Nanjing Agricultural University , , ,","place":["Nanjing, PR China, 210095"]},{"name":"Ministry 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Food Chem."},{"key":"2026072910065561200_cit31","doi-asserted-by":"publisher","first-page":"2935","DOI":"10.1021\/acs.jafc.3c04595","article-title":"Design and Synthesis\nof Novel Diphenyl Ether\nCarboxamide Derivatives To Control the Phytopathogenic Fungus","volume":"72","author":"He","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"2026072910065561200_cit32","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1021\/acs.jafc.6b05134","article-title":"Structure-Based\nDiscovery of Potential Fungicides as\nSuccinate Ubiquinone Oxidoreductase Inhibitors","volume":"65","author":"Xiong","year":"2017","journal-title":"J. Agric. 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Med.\nChem."},{"issue":"67","key":"2026072910065561200_cit35","doi-asserted-by":"publisher","first-page":"13892","DOI":"10.1021\/acs.jafc.9b05942","article-title":"Novel1,3,4-Oxadiazole-2-carbohydrazides\nas Prospective Agricultural Antifungal Agents Potentially Targeting\nSuccinate Dehydrogenase","volume":"67","author":"Wu","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"2026072910065561200_cit36","doi-asserted-by":"publisher","first-page":"110727","DOI":"10.1016\/j.ijfoodmicro.2024.110727","article-title":"The potential of antifungal peptides derived from Lactiplantibacillus\nplantarum WYH for biocontrol of Aspergillus flavus contamination","volume":"418","author":"Ou","year":"2024","journal-title":"Int. J. 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Sci."},{"key":"2026072910065561200_cit40","doi-asserted-by":"publisher","first-page":"2982","DOI":"10.1073\/pnas.1800195115","article-title":"Crystal\nstructure of bacterial succinate: quinone oxidoreductase flavoprotein\nSdhA in complex with its assembly factor SdhE","volume":"115","author":"Maher","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026072910065561200_cit41","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1007\/s13238-011-1079-1","article-title":"Thiabendazole inhibits ubiquinone\nreduction activity of mitochondrial\nrespiratory complex II via a water molecule mediated binding feature","volume":"2","author":"Zhou","year":"2011","journal-title":"Protein Cell"},{"key":"2026072910065561200_cit42","doi-asserted-by":"publisher","first-page":"14001","DOI":"10.1021\/acs.jafc.0c05646","article-title":"Discovery of Pyrazine-Carboxamide-Diphenyl-Ethers as\nNovel Succinate Dehydrogenase Inhibitors via Fragment Recombination","volume":"68","author":"Li","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"2026072910065561200_cit43","doi-asserted-by":"publisher","first-page":"10130","DOI":"10.1021\/acs.jafc.5c00009","article-title":"Design, Synthesis,\nand Bioactivity Evaluation of Novel Indene Amino Acid Derivatives\nas Succinate Dehydrogenase Inhibitors","volume":"73","author":"Zhang","year":"2025","journal-title":"J. Agric.\nFood 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.5c14526","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/29\/22497\/65986760\/acs.jafc.5c14526.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/29\/22497\/65986760\/acs.jafc.5c14526.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T14:12:31Z","timestamp":1785334351000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jafcau\/article\/74\/29\/22497\/5212627\/Coumarin-Hydrazone-Derivatives-as-Potent-Succinate"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":43,"journal-issue":{"issue":"29","published-online":{"date-parts":[[2026,7,17]]},"published-print":{"date-parts":[[2026,7,29]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jafc.5c14526","relation":{},"ISSN":["0021-8561","1520-5118"],"issn-type":[{"value":"0021-8561","type":"print"},{"value":"1520-5118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]}}}