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

• DOI: 10.1021/acs.jafc.5c00121
• Publication Date: 2025-04-02T03:23:31Z
• Authors: Haolin Yuan; Rongzhang Wu; Yangxiaochun Hu; Jin Zhang; Yue Zhang; Zhihong Wang; Jianfei Huo; Liangfu Tang; Bin Zhao; Zhijin Fan
• Keywords: Oxysterol; Methylene

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