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The extensive use of chemical pesticides has led to growing environmental safety risks and pesticide resistance of various plant pathogens. Therefore, it is an urgent task to explore novel eco\u2010friendly fungicidal agents with high efficacy to combat fungal infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>In this study, we rationally designed a series of novel thymol derivatives by incorporation of the sulfonamide moiety and evaluated their biological activities against plant pathogenic fungi. The bioassay results underscored the remarkable <jats:italic>in vitro<\/jats:italic> antifungal activity of compounds <jats:bold>5m<\/jats:bold> and <jats:bold>5t<\/jats:bold> against <jats:italic>Phytophthora capsici<\/jats:italic> (<jats:italic>P. capsici<\/jats:italic>), with EC<jats:sub>50<\/jats:sub> values of 8.420 and 8.414\u2009<jats:italic>\u03bc<\/jats:italic>g\/mL, respectively. Their efficacies were superior to that of widely used commercial fungicides azoxystrobin (AZO, 20.649\u2009<jats:italic>\u03bc<\/jats:italic>g\/mL) and cabendazim (CAB, 251.625\u2009<jats:italic>\u03bc<\/jats:italic>g\/mL). Furthermore, compound <jats:bold>5v<\/jats:bold> exhibited excellent <jats:italic>in vitro<\/jats:italic> antifungal activity against <jats:italic>Sclerotinia sclerotiorum<\/jats:italic> (<jats:italic>S. sclerotiorum<\/jats:italic>), with an EC<jats:sub>50<\/jats:sub> value of 12.829\u2009<jats:italic>\u03bc<\/jats:italic>g\/mL, significantly outperforming AZO (63.629\u2009<jats:italic>\u03bc<\/jats:italic>g\/mL). <jats:italic>In vivo<\/jats:italic> bioassays demonstrated the impactful activity of compound <jats:bold>5v<\/jats:bold> against <jats:italic>S. sclerotiorum<\/jats:italic>, achieving over 98% curative and protective efficacies at the concentration of 200\u2009<jats:italic>\u03bc<\/jats:italic>g\/mL. Further mechanistic investigations unveiled that compound <jats:bold>5v<\/jats:bold> induced mycelial shrinkage and collapse in <jats:italic>S. sclerotiorum<\/jats:italic>, resulting in organelle damage and the accumulation of antioxidant enzyme activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>The significant antifungal efficacy of the prepared thymol derivatives shall encourage further exploration of compound <jats:bold>5v<\/jats:bold> as a promising candidate to develop novel fungicides for crop protection. \u00a9 2024 Society of Chemical Industry.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ps.8203","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T02:44:46Z","timestamp":1717123486000},"page":"4906-4914","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Discovery of novel piperidine\u2010containing thymol derivatives as potent antifungal agents 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Guizhou University  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Pesticide; Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education Center for R&amp;D of Fine Chemicals of Guizhou University  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhichao","family":"Jin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Pesticide; Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education Center for R&amp;D of Fine Chemicals of Guizhou University  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxing","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Pesticide; Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education Center for 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