Novel furazanoazepines derivatives as SDH inhibitors: Design, synthesis and their fungicidal activities

Plant pathogenic fungi are the damage causes of agriculture and food losses, and novel fungicides is an urgent need for dealing with the increasing resistance. Herein, 37 furazanoazepines derivatives were efficiently synthesized and their Antifungal activities against four phytopathogenic fungi were investigated to obtain many effective compounds. Notably, compound 4h was found to exhibited excellent in vitro and in vivo activity against Alternaria alternata, which was obviously better than the positive control osthole. The scanning electron microscopy (SEM) study revealed that compound 4h could cause significant morphological damage of hyphae. Molecular docking indicated that compound 4h could interact with Succinate Dehydrogenase (SDH) by forming hydrogen bond with the Leu305 residue at the active site. Enzymatic activity assays proved that the compound 4h could inhibit SDH with the IC₅₀ value of 3.59 μg/mL, which was better than that of commercial SDHI boscalid (IC₅₀ value = 4.16 μg/mL). The structure-activity relationships of the compounds were studied by 3D-QSAR analysis to provide guidance for the further modification. It was concluded that furazanoazepines were promising for the further study to explore the potential agricultural fungicides.

3D-QASR; Antifungal activity; Furazanoazepines derivatives; Molecular docking.