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

作者：Yingkun Yan, Ai-ling Bao, Yunfan Wang, Xian-song Xie, Deyuan Wang, Ziquan Deng, Xuesong Wang, Wei Cheng, Weiyi Li, Xiaomei Zhang, Xiaorong Tang · 发表于：Journal of Agricultural and Food Chemistry · 年份：2024 · DOI：10.1021/acs.jafc.3c05730 · 被引用次数：17 · 研究领域：Fungal Plant Pathogen Control、Synthesis and Biological Evaluation、Plant-derived Lignans Synthesis and Bioactivity

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 need 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, and compounds 3c, 3i, 3s, and 3r were found to have significant antifungal effects against S. sclerotiorum with EC 50 values of 0.42 mg/L, 0.33 mg/L, 0.37 mg/L, and 0.40 mg/L, respectively, which were superior to the commercial fungicide fluopyram (EC 50 = 0.47 mg/L). The IC 50 value of compound 3i against the SDH of S. sclerotiorum was 0.63 mg/mL, which was further demonstrated by enzyme activity assays. Scanning electron microscopy showed that 3i had a significant inhibitory effect on S. sclerotiorum . In addition, the fluorescence quenching analysis assay indicated that compound 3i had a similar effect with the positive control fluopyram. Molecular docking exhibited that target compounds with chiral configuration had better affinity than racemic configuration, and 3i possessed stronger...