Antifungal Activity and Potential Mechanisms of New l -Menthol Derivatives against Sclerotinia sclerotiorum Causing Postharvest Sclerotinia Rot

A total of 45 l-menthol derivatives with thiosemicarbazide, semicarbazide, or thiazole structures were designed and synthesized, and the in vitro inhibitory activities were evaluated against seven plant pathogens. Some title compounds exhibited remarkable antifungal activities. Specifically, compound 4n demonstrated a significant antifungal effect against Sclerotinia sclerotiorum with an EC50 value of 1.03 mg/L, outperforming thifluzamide (1.32 mg/L). Furthermore, at a concentration of 200 mg/L, 4n displayed excellent protective (97.5%) and curative (95.7%) effects on S. sclerotiorum-infected carrots. In the phytotoxicity experiment, 4n 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 4n. Additionally, 4n exhibited substantial inhibitory effects on the sclerotium formation and germination of S. sclerotiorum. A further mechanism study revealed that 4n could dose-dependently increase the cell membrane permeability and significantly inhibit the defense/respiration-related enzymes of S. sclerotiorum. The transcriptome analysis suggested that 4n 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 4n 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.