Discovery of novel 3-phenylhydrazone coumarin derivatives as potential antifungal agents against phytopathogenic fungi

Abstract

Plant fungal diseases, such as rice sheath blight caused by Rhizoctonia solani, significantly impact crop yield and quality. To discover novel fungicides, 39 novel 3-phenylhydrazone coumarin compounds were synthesized using natural product modeling and active substructure merging strategies. Their bioactivity was tested against six plant pathogens, including Botrytis cinerea, Alternaria solani, Fusarium graminearum, Rhizoctonia solani, Colletotrichum orbiculare, and Alternaria alternata. The majority of compounds exhibited significant activity against B. cinerea and R. solani. Among them, B1 (4-chloro-3-phenylhydrazone-coumarin derivative) displayed outstanding antifungal efficacy, particularly against C. orbiculare (EC₅₀ value = 0.98 μg/mL) and R. solani (EC₅₀ value = 1.20 μg/mL), comparable to the control fungicide boscalid. Structural optimization revealed that introducing a fluorine group in the phenylhydrazone moiety improved activity. Preliminary mechanistic studies suggest that B1 disrupts cell membranes and mitochondrial function, indicating its potential as a novel fungicide candidate.

Keywords: Antifungal activity; Coumarin; Phenylhydrazone; Phytopathogenic fungi.