Design, Synthesis, and Antifungal Activity of Natural Furan Carboxylic Acid Derivatives as Potential Succinate Dehydrogenase Inhibitors.

In this study, a series of furan amide derivatives were designed and synthesized from natural furan carboxylic acids as starting materials, with the aim of developing potential succinate dehydrogenase (SDH) inhibitors. The antifungal activities of the target compounds against four species of plant-pathogenic fungi were evaluated using in vitro bioassays. Structure-activity relationship (SAR) analysis revealed that the introduction of a trifluoromethyl group imparted superior antifungal activity to the compounds. Notably, compound 3m exhibited the most potent inhibitory effect against Rhizoctonia solani, with an EC50 value of 0.418 µg/mL, which was significantly better than that of the control agent Fenfuram. Meanwhile, compound 6b also demonstrated strong inhibitory activity against Fusarium oxysporum, with an EC50 value of 10.723 µg/mL, likewise markedly outperforming Fenfuram. Further in vivo antifungal experiments confirmed that compounds 3m and 6b achieved satisfactory control efficacy against R. solani and F. oxysporum, respectively. These results indicate promising application prospects for compounds 3m and 6b. Mechanistic investigations involving microscopic observation, SDH enzyme activity assays, and molecular docking provided further insight into the potential mode of action of 3m and 6b. The results indicate that compounds 3m and 6b represent structurally optimized lead candidates for the development of novel, natural product-derived fungicides.