Synthesis and antifungal activity of coumarin derivatives containing hydrazone moiety

Plant disease control mainly relies on pesticides. In this study, a series of coumarin derivatives containing hydrazone moiety were designed and synthesized. The synthesized compounds were characterized and used to evaluate the antifungal activity against four pathogens, Botrytis cinerea, Alternaria solani, Fusarium oxysporum, and Alternaria alternata. The results showed that the inhibition rate of some compounds at 100 µg/mL in 96 hours reached around 70% against A. alternata, higher than that of positive control. The corresponding EC50 values were found at around 30 µg/mL. Finally, the compound 3b was screened out with the lowest EC50 value (19.49 μg/mL). The analysis of SEM and TEM confirmed that the compound 3b can obviously damage the morphological structure of hyphae, resulting in the depletion of the cells by the destruction of membranous structure and leakage of cytoplasmic contents. RNA sequencing showed that compounds 3b mainly affected the pentose phosphate pathway, which in turn caused damage to the cell membrane wall structure and function. Molecular docking showed that compounds 3b fitted the binding pocket of yeast transketolase and interacted with lysine at the hydrazone structure. Our results suggested that the introduction of hydrazone was an effective strategy for the design of novel bioactive compounds