Discovery of Novel Carbohydrazide-Containing Formononetin Derivatives as Potential Broad-Spectrum Antifungal Agents.

A series of formononetin derivatives containing carbohydrate structures were designed and synthesized, and the in vitro antifungal activities of these compounds were evaluated. Among them, X4 displayed the most potent antifungal activity against Rhizoctonia solani (Rs), with an EC50 value of 0.58 μg/mL, outperforming azoxystrobin (Az, EC50 = 6.87 μg/mL), fluopyram (Fl, EC50 = 47.74 μg/mL), and boscalid (BC, EC50 = 1.02 μg/mL). In vivo antifungal assays conducted on rice leaves and kiwifruit demonstrated that X4 displayed satisfactory protective and curative effects. Meanwhile, X4 exhibited excellent inhibitory activity against both sclerotium formation and germination of Rs. As verified by scanning electron microscopy (SEM), fluorescence microscopy (FM), and MDA assays, X4 inhibited fungal growth by disrupting the integrity of the mycelial cell membrane and inducing lipid peroxidation. Molecular docking experiments combined with SDH activity assays indicated that X4 engages in favorable interactions with SDH.