Design, Synthesis, Antifungal Activity and Molecular Docking Studies of Novel Chiral Isoxazoline-Benzofuran-Sulfonamide Derivatives

Succinate dehydrogenase (SDH) is one of the most important molecular targets for the development of novel fungicides. With the emerging problem of resistance in plant fungal pathogens, novel compounds with high fungicidal activity are needed to be developed, but the study of chiral pesticides for the inhibition of highly destructive plant pathogens has been rarely reported in recent years. Therefore, a series of novel chiral isoxazoline-benzofuran sulfonamide derivatives were designed to investigate potential novel antifungal molecules. The chiral target compound 3a was cultured as a single crystal and confirmed using X-ray diffraction. All the target compounds were tested for antifungal activity, compounds 3c, 3i, 3s, and 3r were found to have significant antifungal effects against S. sclerotiorum with an EC50 value 0.42 mg/L, 0.33 mg/L, 0.37 mg/L, 0.40 mg/L, respectively, which was superior to the commercial fungicide fluopyram (EC50 = 0.47 mg/L). The IC50 value of compound 3i against S. sclerotiorum was 0.63 mg/mL, which was further demonstrated by enzyme activity assay. Scanning electron microscopy showed that 3i had a significant inhibitory effect on S. sclerotiorum. Fluorescence quenching analysis assay indicated that compound 3i had a similar effect with the positive control fluopyram. Molecular docking studies exhibited that the title compounds with absolute configuration had better affinity than relative configuration, 3i possessed stronger action than fluopyram, which was in keeping with the in vitro test results. These results would provide a basis and reference for the development of novel chiral fungicides.