Discovery of Bacillamide–Acylhydrazone Hybrids as Novel Fungicide Lead Compounds

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 <i>B. cinerea</i>. Among them, compound <b>BAD-15</b> 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 <b>BAD-15</b> 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 <b>BAD-15</b> may serve as a potential lead compound for the further development of novel fungicides.