Abstract：
Corn ear rot and fumonisin caused by Fusarium verticillioides pose a serious threat to food security. To find more highly active fungicidal and antitoxic candidates with structure diversity based on naturally occurring lead xanthatin, a series of novel spiropiperidinyl-α-methylene-γ-butyrolactones were rationally designed and synthesized. The in vitro bioassay results indicated that compound 7c showed broad-spectrum in vitro activity with EC50 values falling from 3.51 to 24.10 μg/mL against Rhizoctonia solani and Alternaria solani, which was more active than the positive controls xanthatin and oxathiapiprolin. In addition, compound 7c also showed good antitoxic efficacy against fumonisin with a 48% inhibition rate even at a concentration of 20 μg/mL. Fluorescence quenching and the molecular docking validated both 7c and oxathiapiprolin targeting at FvoshC. RNA sequencing analysis discovered that FUM gene cluster and protein processing in endoplasmic reticulum were downregulated. Our studies have discovered spiropiperidinyl-α-methylene-γ-butyrolactone as a novel FvoshC target-based scaffold for fungicide lead with antitoxin activity.
摘要：
玉米穗腐病和轮枝镰刀菌引起的伏马菌素对粮食安全构成严重威胁。为了找到更高活性的杀真菌和抗毒候选物，具有基于天然存在的铅黄素的结构多样性，合理设计合成了一系列新型螺哌啶基-α-亚甲基-γ-丁内酯。体外生物测定结果表明，化合物7c具有广谱的体外活性，其EC50值从3.51降至24.10μg/mL，比阳性对照黄原苷和奥齐哌林更活跃。此外,即使在20μg/mL的浓度下，化合物7c也对伏马菌素具有48％的抑制率。荧光猝灭和分子对接验证了7c和氧硫哌林在FvoshC的靶向性。RNA测序分析发现，内质网中的FUM基因簇和蛋白质加工下调。我们的研究发现螺哌啶基-α-亚甲基-γ-丁内酯是一种新型的基于FvoshC靶标的支架，具有抗毒素活性。
