Design, synthesis and fungicidal evaluation of novel pyraclostrobin analogues

Abstract

A series of novel pyraclostrobin derivatives were designed and prepared as antifungal agents. Their antifungal activities were tested in vitro with five important phytopathogenic fungi, namely, Batrylis cinerea, Phytophthora capsici, Fusarium sulphureum, Gloeosporium pestis and Sclerotinia sclerotiorum using the mycelium growth inhibition method. Among these compounds, 5s displayed IC₅₀ value of 0.57 μg/mL against Batrylis cinerea and 5k-II displayed IC₅₀ value of 0.43 μg/mL against Sclerotinia sclerotiorum, which were close to that of the positive control pyraclostrobin (0.18 μg/mL and 0.15 μg/mL). Other compounds 5f, 5k-II, 5j, 5m and 5s also exhibited strong antifungal activity. Further enzymatic assay demonstrated compound 5s inhibited porcine bc₁ complex with IC₅₀ value of 0.95 μM. The statistical results from an integrated computational pipeline demonstrated the predicted total binding free energy for compound 5s is the highest. Consequently, compound 5s with the biphenyl-4-methoxyl side chain could serve as a new motif as inhibitors of bc₁ complex and deserve to be further investigated.

Keywords: Antifungal activity; Cytochrome bc(1) complex inhibitor; Molecular docking; Phytopathogenic fungi; Pyraclostrobin analogues.