Synthesis, Fungicidal Activity, and Action Mode of Functionalized Siderophores

Abstract

Iron homeostasis influences fungal pathogenicity and is a promising target for crop protection. In this study, catechol moieties were incorporated into G2-class fungicidal scaffolds to prepare a series of siderophores. At 50 μg/mL, the compounds PP-3 and PPDM-2 achieved mean inhibition rates (MIRs) of 64.0% and 67.2%, respectively, against 11 plant pathogens, comparable to tridemorph (64.6%). However, the two compounds exhibited distinct activity spectra. PP-3 and PPDM-2 showed strong activity against two oomycete pathogens (Pythium aphanidermatum and Phytophthora capsici) and Fusarium graminearum, suggesting potential for crop disease management. Preliminary assays indicated disruption of Fe3+/Fe2+ homeostasis and rapid ion leakage through nonspecific membrane lipid perturbation; inhibition of ergosterol biosynthesis may additionally contribute to activity against fungi. These findings support the development of agricultural fungicides incorporating functional iron-chelating moieties.