Amide derivatives as potential SDH inhibitors: Design, synthesis, antifungal activity, and preliminary mechanism

Plant pathogenic fungi cause plant diseases that affect global food security, and the use of chemical fungicides remains the primary strategy for controlling fungal diseases. A series of amide derivatives containing 3-chloro-5-trifluoromethyl pyridine and piperidine structures was designed and synthesized, and their antifungal activity was systematically evaluated. Among them, compound M3 exhibited excellent fungicidal efficacy against Rhizoctonia solani (R. s) (EC₅₀ = 3.24 mg/L), with a curative effect of 69.98% at 200 mg/L in rice plants. Compound M3 inhibited the mycelial dry weight and sclerotial formation of R. s, as well as disrupted the mycelial morphology and ultrastructure, increasing cell membrane permeability, leakage of cell contents, and accumulation of reactive oxygen species (ROS), ultimately leading to fungal death, thus suppressing its growth and reproduction. Compound M3 significantly inhibited succinate dehydrogenase (SDH) activity (IC₅₀ = 28.40 μM), and molecular docking results also indicated a stable binding mode between compound M3 and SDH.