Synthesis and Antifungal Activities of Schiff Base Derivatives Containing a Coumarin Moiety

Naturally derived compounds often exhibit promising bioactivity. Coumarin is an important secondary metabolite widely found in various plants and fruits. In this work, a total of 30 novel Schiff base derivatives incorporating a coumarin moiety were synthesized and characterized using ¹H NMR, ¹³C NMR, and HR-MS spectroscopies. The in vitro fungicidal activity of these compounds against four phytopathogenic fungi (Alternaria solani (A. solani), Fusarium oxysporum (F. oxysporum), Botrytis cinerea (B. cinerea), and Alternaria alternata (A. alternata)) was systematically evaluated. Notably, compounds 3g, 3h, and 3m demonstrated remarkable antifungal activity in vitro, achieving inhibition rates exceeding 90% against both B. cinerea and F. oxysporum at a concentration of 100 μg/mL after 72 h of treatment. Compound 3m, in particular, exhibited exceptionally low EC₅₀ values against B. cinerea (1.62 μg/mL) and F. oxysporum (2.50 μg/mL), dramatically outperforming the positive control (boscalid) (10.75 and 118.81 μg/mL, respectively) and highlighting the potential as a promising antifungal agent. The in vivo efficacy of compound 3m against B. cinerea was also investigated, showing robust activity in suppressing fungal growth on the pear fruits. At 400 μg/mL, it achieved a curative efficacy of 94.3% after 7 days. SEM and TEM analyses of hyphae revealed that the antifungal agent disrupted cellular integrity, causing the leakage of intracellular contents and abnormal mitochondrial morphology. Moreover, compound 3m exhibited high inhibitory activity of succinate dehydrogenase (SDH) with an IC₅₀ value of 0.46 μg/mL, suggesting its role as an inhibitor of SDH. Molecular docking supported that compound 3m had a strong affinity with SDH via hydrogen bonds, thereby exerting its inhibitory effect. These findings offer valuable insights and lay a foundation for the development of novel fungicides to combat plant diseases.