Synthesis and Antifungal Activity of Norbornene Carboxamide/sulfonamide Derivatives as Potential Fungicides Targeting Laccase

Abstract

To explore more potential fungicides with new scaffolds, thirty‐seven norbornene carboxamide/sulfonamide derivatives were designed, synthesized, and assayed for inhibitory activity against six plant pathogenic fungi and oomycetes. The preliminary antifungal assay suggested that the title derivatives showed moderate to good antifungal activity against six plant pathogens. Especially, compound 6e presented excellent in vitro antifungal activity against Sclerotinia sclerotiorum (EC50 = 0.71 mg/L), which was substantially stronger than pydiflumetofen. In vivo antifungal assay indicated 6e displayed prominent protective and curative effects on rape leaves infected by S. sclerotiorum. The preliminary mechanism research displayed that 6e could damage the surface morphology and inhibit the sclerotia formation of S. sclerotiorum. In addition, the in vitro enzyme inhibition bioassay indicated that 6e displayed pronounced laccase inhibition activity (IC50 = 0.63 μM), much stronger than positive control cysteine. Molecular docking elucidated the binding modes between 6e and laccase. The bioassay results and mechanism investigation demonstrated that this class of norbornene carboxamide/sulfonamide derivatives could be promising laccase inhibitors for novel fungicide development.