基于两种特权支架的组合设计了新型杀菌剂,硫代乙内酰脲和螺环丁烯酸内酯,广泛存在于天然产品中。合成的化合物通过1HNMR表征,13CNMR,和高分辨率电喷雾电离质谱。体外抗卵菌活性评估表明,大多数化合物对致病卵菌辣椒疫霉生命周期中的不同发育阶段表现出优异的抑制活性。化合物5j可抑制菌丝生长,孢子囊生产,游动孢子释放,和囊孢子萌发显着,EC50值为0.38、0.25、0.11和0.026μg/mL,分别。体内抗真菌/抗卵菌生物测定结果表明,该系列化合物通常对致病性卵菌Pseudoperonosporacubensis表现出出色的控制效果,和化合物5j,5l,7j,7k,7l对试验植物病原菌具有广谱抗真菌活性。代表性化合物5j对辣椒假单胞菌的体内保护和治疗效果优异,它比唑菌酯好.更突出的是,5j显著促进了根系的生物量积累,并通过call体沉积增强了细胞壁。免疫反应相关基因的明显上调表明,活性卵菌抑制剂5j也起着植物诱导子的作用。透射电镜观察和酶活性测试表明,5j的作用机制是与关键蛋白结合,呼吸链上的复合物III,导致能源供应短缺。分子对接结果表明,化合物5j与Qo口袋适当匹配,并且与最常见的突变位点Gly-142没有相互作用,这在Qo杀真菌剂抗性管理中可能具有显著益处。化合物5j在卵菌控制中显示出巨大的优势和潜力,阻力管理,并诱导抗病性。对具有独特结构的5j的进一步研究可能对创建针对植物致病性卵菌的新型卵菌抑制剂具有直接意义。
Novel fungicidal agents were designed based on the combination of two privileged scaffolds,
thiohydantoin and spirocyclic butenolide, which are widely found in natural products. The synthesized compounds were characterized by 1H NMR, 13C NMR, and high-resolution electrospray ionisation mass spectrometry. The in vitro antioomycete activity evaluation showed that most of the compounds exhibited excellent inhibitory activities against different developmental stages in the life cycle of pathogenic oomycete Phytophthora capsici. Compound 5j could inhibit the mycelial growth, sporangium production, zoospore release, and cystospore germination significantly with EC50 values of 0.38, 0.25, 0.11, and 0.026 μg/mL, respectively. The in vivo antifungal/antioomycete bioassay results revealed that the series of compounds generally showed outstanding control efficacies against the pathogenic oomycete Pseudoperonospora cubensis, and compounds 5j, 5l, 7j, 7k, and 7l possessed broad-spectrum antifungal activities against the test phytopathogens. The in vivo protective and curative efficacies against P. capsici of the representative compound 5j were excellent, which were better than those of azoxystrobin. More prominently, 5j significantly promoted the biomass accumulation of the root system and reinforced the cell wall by callose deposition. The pronounced upregulation of immune response-related genes indicated that the active oomycete inhibitor 5j also functioned as a plant elicitor. Transmission electron microscopy observation and the enzyme activity test demonstrated that the mechanism of action of 5j was to bind to the pivotal protein, complex III on the respiratory chain, which resulted in a shortage of energy supply. Molecular docking results exhibited that compound 5j appropriately matched with the Qo pocket and had no interaction with the most commonly mutated site Gly-142, which may be of significant benefit in Qo fungicide resistance management. Compound 5j showed great advantages and potential in oomycete control, resistance management, and induction of disease resistance. A further investigation of 5j with a unique structure might have direct implications for the creation of novel oomycete inhibitors against plant-pathogenic oomycetes.