To identify fungicide lead compounds with novel scaffolds and high efficacy, 33 novel bacillamide–acylhydrazone derivatives were successfully designed and synthesized by using a molecular hybridization strategy. The bioassay results showed that most of the target compounds exhibited promising inhibitory activity against B. cinerea. Among them, compound BAD-15 displayed the most potent antifungal activity with an EC50 value of 6.725 μg/mL. Furthermore, preliminary SAR analysis revealed that the R group in hydrazine fragments exerts a significant influence on antifungal potency. Studying the molecular mechanism by morphological observation and transcriptome analyses revealed that BAD-15 may inhibit the activity of copper ion transmembrane transporters, leading to disrupted copper ion homeostasis and subsequent suppression of fungal growth. The present work indicates that bacillamide–acylhydrazone has potential as a novel scaffold for the development of fungicides, and compound BAD-15 may serve as a potential lead compound for the further development of novel fungicides.
Feng et al. (Thu,) studied this question.