Design, Synthesis, and Multifaceted Antifungal Mechanism of Novel Indole Amide Derivatives for Sustainable Crop...

Seventy-eight novel indole amide derivatives based on N-indoleacetic acid and indole-3-propionic acid were designed and synthesized as potential antifungal agents for sustainable crop protection. Among them, F18 exhibited potent antifungal activity against Rhizoctonia solani, Sclerotinia sclerotiorum, and Pestalotiopsis piricola, with EC₅₀ values of 3.63, 12.38, and 2.43 μg/mL, respectively, whereas F20 showed excellent activity against R. solani (EC₅₀ = 1.60 μg/mL). In vivo, F18 and F20 provided protective efficacies of 88.2 and 89.1%, respectively, against rice sheath blight at 200 μg/mL, exceeding that of the commercial fungicide tebuconazole (75.6%). Mechanistic studies showed that F18 disrupted fungal cell morphology, induced reactive oxygen species accumulation, and impaired mitochondrial function. Molecular docking suggested that F18 could bind within the putative ubiquinone-binding pocket of the succinate dehydrogenase complex, supporting SDH-associated mitochondrial dysfunction. These results identify F18 and F20 as promising lead compounds for sustainable fungicide development.