A novel bridged Dicarboximide derivative: A highly effective antifungal agent for managing plant pathogens.

Increasing resistance to dicarboximide fungicides (DCFs) and their associated environmental risks necessitate the development of novel and eco-friendly antifungal agents. In this study, a series of novel DCF derivatives (C1-C34) were designed and synthesized by introducing an oxygen bridge and halogen substituents into an oxabicyclo[2.2.1]alkane scaffold, and their activities were compared with those of carbon-bridged analogs. Compound C34 displayed outstanding broad-spectrum antifungal efficacy, particularly against Botrytis cinerea, with an EC50 value of 0.18 mg/L, exceeding that of the commercial fungicide dimethachlon (EC50 = 0.37 mg/L). In vivo assays using tomato fruits further verified the protective and curative effects of C34. Mechanistic investigations using scanning and transmission electron microscopy (SEM/TEM) revealed that C34 causes severe hyphal damage, including plasma membrane detachment and organelle degradation. Transcriptomic analysis combined with molecular docking suggested that the antifungal activity of C34 may involve interference with metabolic pathways and inhibition of histidine kinase, with stable binding to key amino acid residues. Notably, acute zebrafish toxicity assays demonstrated that C34 exhibits a markedly improved safety profile (LC50 > 40 mg/L) compared with dimethachlon. Overall, these results identify C34 as a promising low-toxicity lead compound for sustainable crop protection.