Antifungal Activity and Potential Mechanisms of New <scp>l</scp> -Menthol Derivatives against <i>Sclerotinia sclerotiorum</i> Causing Postharvest Sclerotinia Rot

A total of 45 l-menthol derivatives with thiosemicarbazide, semicarbazide, or thiazole structures were designed and synthesized, and the <i>in vitro</i> inhibitory activities were evaluated against seven plant pathogens. Some title compounds exhibited remarkable antifungal activities. Specifically, compound <b>4n</b> demonstrated a significant antifungal effect against <i>Sclerotinia sclerotiorum</i> with an EC₅₀ value of 1.03 mg/L, outperforming thifluzamide (1.32 mg/L). Furthermore, at a concentration of 200 mg/L, <b>4n</b> displayed excellent protective (97.5%) and curative (95.7%) effects on <i>S. sclerotiorum</i>-infected carrots. In the phytotoxicity experiment, <b>4n</b> exhibited no effect on the normal germination of carrot and mung bean seeds. Fluorescence imaging revealed a significant accumulation of reactive oxygen species (ROS) in mycelia treated with <b>4n</b>. Additionally, <b>4n</b> exhibited substantial inhibitory effects on the sclerotium formation and germination of <i>S. sclerotiorum</i>. A further mechanism study revealed that <b>4n</b> could dose-dependently increase the cell membrane permeability and significantly inhibit the defense/respiration-related enzymes of <i>S. sclerotiorum</i>. The transcriptome analysis suggested that <b>4n</b> could notably affect the gene expression related to the oxidation-reduction process and oxidoreductase activity. The enzyme inhibition assay and molecular docking studies implied that <b>4n</b> could be a potential succinate dehydrogenase (SDH) inhibitor. These findings indicated that this class of l-menthol thiosemicarbazide derivatives holds promise as potential fungicides for the prevention and treatment of postharvest sclerotinia rot.