Fungicidal Activity of Carboxamides Containing Spiropiperidinyl-α-methylene-γ-butyrolactones Targeting Oxysterol...

Oxysterol binding protein (OSBP) is a new target for oomycide development. To find more fungicidal active compounds targeting OSBP, a series of carboxamides containing spiropiperidinyl-α-methylene-γ-butyrolactone and heterocyclic carboxylic acids were rationally designed and synthesized by using a computer-aided pesticide design method. The in vitro fungicidal bioassay found that compound 5o showed broad-spectrum activity with EC₅₀ values falling between 0.50 and 20.85 μg/mL against Phytophthora capsici and Fusarium verticillioides, respectively, which was more potent than 7c and natural lead xanthatin. Compound 5o also showed 44% in vivo efficacy against Pseudoperonospora cubensis, even at a concentration of 0.5 μg/mL. Fluorescence quenching and microscale thermophoresis determination suggested that compound 5o bound to Osh4p and showed stronger interactions than oxathiapiprolin. RNA sequencing analysis discovered that the ergosterol (ERG) gene cluster and ribosome biogenesis in eukaryotes were downregulated. Compound 5o was discovered as a good fungicidal candidate targeting OSBP deserving further studies.