Thiosulfonates Based on Prothioconazole for Enhancing Antifungal Activity and Mitigating Phytotoxicity in Plant Pathogen Management

Prothioconazole (Prot) has been widely used for over two decades in controlling cereal diseases. However, the continuous emergence of resistance in plant pathogens has necessitated the development of novel fungicides. Thiosulfonate compounds have great application prospects due to their unique structural features and multisite activity. Herein, 25 novel Prot-based thiosulfonates were synthesized, and related antifungal activities were evaluated. Among them, 17 arylthiosulfonates exhibited better antifungal efficacy against Fusarium graminearum (EC50 = 0.07-0.22 mg/L) than Prot (EC50 = 0.41 mg/L). Interestingly, the most efficient compound, Tosyl-Prot (I-08) could be hydrolyzed to Prot in the environment and exhibited superior safety toward germination of wheat seed (86.67%) compared to Prot (0%). The antifungal mechanism of compound I-08 was demonstrated by disrupting the membrane integrity, inhibiting biomass accumulation, and suppressing multiple metabolic pathways. Therefore, Prot-based thiosulfonates would offer innovative strategies for the development of next-generation agricultural fungicides with multimodal actions and enhanced environmental compatibility.