{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T03:16:00Z","timestamp":1788318960305,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["scijournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pest Management Science"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Succinate dehydrogenase inhibitors (SDHIs) represent one of the most important fungicide subclasses for the chemical control of plant diseases. The identification of novel SDHIs with innovative scaffolds through virtual screening is crucial for pathogenic fungi management and food security.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>A novel carbothioate hit compound was identified through a hierarchical virtual screening protocol with novel <jats:italic>\u03b2<\/jats:italic>\u2010ketonitrile fungicidal compound as query structure. The structural optimization resulted optimal compound <jats:bold>A12<\/jats:bold> showed good <jats:italic>in vitro<\/jats:italic> broad\u2010spectrum fungicidal activities against <jats:italic>Rhizoctonia solani, Sclerotiorum sclerotiorum, Botrytis cinerea and Fusarium graminearum<\/jats:italic>, with EC<jats:sub>50<\/jats:sub> values of 4.38, 10.76, 7.69, and 10.28\u2009\u03bcg\/mL, respectively. <jats:bold>A12<\/jats:bold> also exhibited promising <jats:italic>in vivo<\/jats:italic> protective efficacy against rice sheath blight. Scanning electron microscopy (SEM) observation and SDH enzymatic assays revealed that <jats:bold>A12<\/jats:bold> served as a potent SDH inhibitor, with an IC<jats:sub>50<\/jats:sub> value of 4.53\u2009\u03bcM. Computational binding mode research demonstrated that <jats:bold>A12<\/jats:bold> formed H\u2010bonds, cation\u2010\u03c0 and T\u2010\u03c0 interaction with SDH.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>The identified optimal carbothioate compound <jats:bold>A12<\/jats:bold> served as a potent lead compound for further structural optimization as potential agricultural SDHI fungicides. \u00a9 2025 Society of Chemical Industry.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ps.8795","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T23:55:10Z","timestamp":1743206110000},"page":"4373-4381","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Hit to lead optimization of carbothioate derivatives as novel succinate dehydrogenase inhibitors using a multistep virtual screening 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