Synthesis of 4-(Diethylamino)salicylaldehyde Derivatives and Research on Their Antifungal Mechanism against Rhizoctonia solani

To enhance the antifungal activity of 4-(diethylamino)salicylaldehyde (DSA), 20 salicylaldehyde Schiff base compounds (L1–L20), including nine novel derivatives, were synthesized and characterized by MS, 1 H NMR, and 13 C NMR. In vitro assays identified compound L5 as the most active agent, with an EC 50 of 10.797 μg/mL (2-fold higher than DSA), and pot experiments confirmed its efficacy against cotton damping-off disease. Mechanistic investigations via electron microscopy, transcriptomics, physiological assays and molecular docking suggest that L5 may target fatty acid synthase (FAS) to interfere with fungal lipid biosynthesis, disrupt energy homeostasis, and induce oxidative stress, which triggers synergistic membrane impairment and oxidative damage and ultimately causes hyphal death. With a novel target and a distinctive single-target, multieffect mode of action, L5 is a promising candidate for new fungicide development.