{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:16:17Z","timestamp":1788455777847,"version":"build-2803163510"},"reference-count":32,"publisher":"American Chemical Society (ACS)","issue":"34","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100009084","name":"Ningxia University","doi-asserted-by":"publisher","award":["NXY202621"],"award-info":[{"award-number":["NXY202621"]}],"id":[{"id":"10.13039\/100009084","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32402423"],"award-info":[{"award-number":["32402423"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004772","name":"Natural Science Foundation of Ningxia Province","doi-asserted-by":"publisher","award":["2024AAC03138"],"award-info":[{"award-number":["2024AAC03138"]}],"id":[{"id":"10.13039\/501100004772","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Sterol 14\u03b1-demethylase (CYP51) and squalene epoxidase (SE) are rate-limiting enzymes in ergosterol biosynthesis, and their inhibition markedly retards fungal growth. A series of novel (1,2,4-triazol-1-yl)propan-2-ol derivatives were designed based on reported CYP51\/SE inhibitor scaffolds. Bioassays demonstrated that compound 6o exhibited broad-spectrum antifungal activity, with EC50 values of 0.25, 0.38, and 0.49 mg\/L against Valsa mali, Rhizoctonia solani, and Curvularia lunata, respectively. At 100 mg\/L, compound 6o achieved 84.6% in vivo control efficacy against V. mali, comparable to difenoconazole (88.1%). Further studies revealed that compound 6o blocked ergosterol synthesis, damaged cell membrane integrity, elevated membrane permeability, and triggered intracellular ROS accumulation in V. mali. Enzyme activity tests, molecular docking, and qRT-PCR analyses suggested that compound 6o acts as a dual inhibitor of CYP51 and SE. Moreover, compound 6o exhibited good biosafety toward apple and rice seedlings. Collectively, compound 6o represents a promising lead for novel demethylation inhibitor fungicides for crop protection.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c05380","type":"journal-article","created":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T12:42:41Z","timestamp":1788093761000},"page":"27286-27297","source":"Crossref","is-referenced-by-count":0,"title":["Discovery, Optimization, and Biological Evaluation\nof Novel (1,2,4-Triazol-1-yl)propan-2-ol Derivatives as Potent Demethylation\nInhibitors"],"prefix":"10.1021","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0574-8602","authenticated-orcid":true,"given":"Jian-Wei","family":"Xue","sequence":"first","affiliation":[{"name":"Ningxia University , , , ,","place":["Yinchuan, Ningxia, China, 750021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Luo","sequence":"additional","affiliation":[{"name":"Ningxia University , , , ,","place":["Yinchuan, Ningxia, China, 750021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun-Bai","family":"Chen","sequence":"additional","affiliation":[{"name":"Ningxia University , , , ,","place":["Yinchuan, Ningxia, China, 750021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Ningxia University , , , ,","place":["Yinchuan, Ningxia, China, 750021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Jie","family":"Yu","sequence":"additional","affiliation":[{"name":"Ningxia University , , , ,","place":["Yinchuan, Ningxia, China, 750021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8072-4938","authenticated-orcid":true,"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Ningxia University , , , ,","place":["Yinchuan, Ningxia, China, 750021"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"issue":"31","key":"2026090311501533300_cit1","doi-asserted-by":"publisher","first-page":"17608","DOI":"10.1021\/acs.jafc.4c02685","article-title":"Discovery, Optimization, and Biological Evaluation\nof Novel Pyrazol-5-yl-phenoxybenzamide Derivatives as Potent Succinate\nDehydrogenase Inhibitors","volume":"72","author":"Xu","year":"2024","journal-title":"J. Agric. Food Chem."},{"issue":"10","key":"2026090311501533300_cit2","doi-asserted-by":"publisher","first-page":"1844","DOI":"10.1002\/ps.4216","article-title":"Efficacy of\nSDHI fungicides, including benzovindiflupyr, against Colletotrichum\nspecies","volume":"72","author":"Ishii","year":"2016","journal-title":"Pest Manage. Sci."},{"key":"2026090311501533300_cit3","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.ejmech.2016.04.060","article-title":"Design, synthesis and antifungal\nactivity of novel furancarboxamide derivatives","volume":"120","author":"Wen","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"2026090311501533300_cit4","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.pestbp.2019.02.017","article-title":"Design,\nsynthesis, and antifungal activity of carboxamide derivatives possessing\n1,2,3-triazole as potential succinate dehydrogenase inhibitors","volume":"156","author":"Yan","year":"2019","journal-title":"Pestic. Biochem. 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Agric. Food Chem."},{"issue":"5","key":"2026090311501533300_cit29","doi-asserted-by":"publisher","first-page":"2830","DOI":"10.1021\/acs.jafc.4c09461","article-title":"Discovery of New Benzohydrazide\nDerivatives Containing 4-Aminoquinazoline as Effective Agricultural\nFungicides, the Related Mechanistic Study, and Safety Assessment","volume":"73","author":"Liu","year":"2025","journal-title":"J. Agric. Food Chem."},{"issue":"44","key":"2026090311501533300_cit30","doi-asserted-by":"publisher","first-page":"28081","DOI":"10.1021\/acs.jafc.5c08379","article-title":"Design\nand Discovery of Pyrazolo[1,5-a]pyrimidinyl\nOxazoline as a Promising Antifungal Model","volume":"73","author":"Fu","year":"2025","journal-title":"J.\nAgric. Food Chem."},{"issue":"4","key":"2026090311501533300_cit31","doi-asserted-by":"publisher","first-page":"2856","DOI":"10.1002\/ps.70353","article-title":"Design, synthesis\nand bioactivity\nstudies of flavonol bio-containing \u03b2-amino\nalcohols","volume":"82","author":"Qiu","year":"2026","journal-title":"Pest Manage. Sci."},{"issue":"9","key":"2026090311501533300_cit32","doi-asserted-by":"publisher","first-page":"4066","DOI":"10.1021\/acs.jmedchem.5b00104","article-title":"pkCSM:\nPredicting small-molecule\npharmacokinetic and toxicity properties using graph-based signatures","volume":"58","author":"Pires","year":"2015","journal-title":"J. Med. 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