Discovery of α-Methylene-γ-Butyrolactone Derivatives with Hydrazide Moieties as Novel Fungicidal Agents.

To discover novel fungicides with unique structures, a series of α-methylene-γ-butyrolactone derivatives were designed and synthesized by incorporating a flexible amide or hydrazide chain through active substructure splicing and linker modification strategies. Bioassay assessments demonstrated that certain hydrazide-containing compounds have potent fungicidal efficacy. Notably, compound exhibited broad-spectrum antifungal activity, with EC values as low as 0.179, 0.301, 0.647, 0.549, and 0.789 mg/L against , , , and , respectively. experiments confirmed the effective fungicidal activity of compound , showing an inhibitory rate of 69.7% against on apple twigs at 200 mg/L. Additionally, at a concentration of 100 mg/L, compound demonstrated significant protective and curative effects against on rice plants. Research on the mechanism of action revealed that compound could disrupt hyphal morphology, induce reactive oxygen species (ROS) accumulation, affect mitochondrial membrane potential (MMP), and interfere with respiratory metabolism by binding to complex II. Molecular docking analysis showed significant interactions of compound with TRP 173, TYR 58, and ARG 43 in the succinate dehydrogenase (SDH) binding site, resembling the binding mode of . These findings suggest that compound holds potential as an SDH inhibitor for agricultural disease control.