Discovery of Thiram-Inspired Thiocarbamate Derivatives as Novel Laccase Inhibitors against Sclerotium rolfsii

Abstract Peanut stem rot, caused by the soil-borne pathogen Sclerotium rolfsii, poses a significant threat to global peanut production and results in substantial yield losses. A series of thiocarbamate derivatives were synthesized and evaluated against ten phytopathogenic fungi. Over 50% showed broad-spectrum fungicidal activity at 40 mg/L. Notably, compound b6 exhibited superior activity against S. rolfsii (EC50 = 0.75 mg/L), surpassing Thiram (EC50 = 0.91 mg/L). In vivo assays confirmed robust protective and curative efficacies on peanut seedlings. b6 also demonstrated potent laccase inhibition (IC50 = 0.064 mmol/L), significantly outperforming l-cysteine (IC50 = 0.551 mmol/L) and PMDD-5Y (IC50 = 0.326 mmol/L). Mechanistic studies revealed that b6 disrupts fungal cell membrane integrity and induces intracellular ROS accumulation. Overall, b6 represents a promising antifungal lead compound for designing novel laccase inhibitor-based fungicides.