Novel N ′-Phenyl Benzyl Carbazate Derivatives with Potent Multiple Antifungal Activity: Design, Structure–Activity Relationship, and Action Mode

The development of new fungicides has been a requirement for agricultural production, food safety, and the advancement of pesticides. In this study, 30 N′-phenyl benzyl carbazates were designed through the fusion of multiple antifungal pharmacophores to find promising fungicide candidates. Twenty-six compounds exhibited average EC50 values of 0.316–4.617 μg/mL against six phytopathogenic fungi, superior to carbendazim and boscalid against half or more of the fungi. Half of the compounds displayed average EC50 values of <1.0 μg/mL against all the fungi. N′-4-chlorophenyl derivative (2f) revealed 96.3% control efficacy against A. solani on tomato fruits at 200 μg/mL on the seventh day, with low toxicity to plant and mammalian cells. The action mode demonstrated that 2f disrupted cell ultrastructure, altered intracellular ROS level, MMP, mycelial morphology, and cell membrane integrity, and inhibited SDH activity. Consequently, the present compounds have great potential for developing novel agricultural fungicides.