PDF(Pubmed)
Abstract：
Phytopathogenic fungi cause plant diseases and economic losses in agriculture. To efficiently control plant pathogen infections, a total of 19 spirotryprostatin A derivatives and 26 spirooxindole derivatives were designed, synthesized, and tested for their antifungal activity against ten plant pathogens. Additionally, the intermediates of spirooxindole derivatives were investigated, including proposing a mechanism for diastereoselectivity and performing amplification experiments. The bioassay results demonstrated that spirotryprostatin A derivatives possess good and broad-spectrum antifungal activities. Compound 4d exhibited excellent antifungal activity in vitro, equal to or higher than the positive control ketoconazole, against Helminthosporium maydis, Trichothecium roseum, Botrytis cinerea, Colletotrichum gloeosporioides, Fusarium graminearum, Alternaria brassicae, Alternaria alternate, and Fusarium solan (MICs: 8-32 µg/mL). Compound 4k also displayed remarkable antifungal activity against eight other phytopathogenic fungi, including Fusarium oxysporium f. sp. niveum and Mycosphaerella melonis (MICs: 8-32 µg/mL). The preliminary structure-activity relationships (SARs) were further discussed. Moreover, molecular docking studies revealed that spirotryprostatin A derivatives anchored in the binding site of succinate dehydrogenase (SDH). Therefore, these compounds showed potential as natural compound-based chiral fungicides and hold promise as candidates for further enhancements in terms of structure and properties.
摘要：
植物病原真菌在农业中引起植物病害和经济损失。为了有效控制植物病原体感染，共设计了19个螺前列腺素A衍生物和26个螺羟吲哚衍生物，合成，并测试了它们对十种植物病原体的抗真菌活性。此外,研究了螺羟吲哚衍生物的中间体，包括提出非对映选择性的机制和进行扩增实验。生物测定结果表明，螺前列腺素A衍生物具有良好的广谱抗真菌活性。化合物4d具有良好的体外抗真菌活性,等于或高于阳性对照酮康唑，对抗蠕虫孢子虫，玫瑰三毛,灰葡萄孢菌,炭疽病，禾谷镰刀菌,油菜链格孢菌,交替菌,和镰刀菌（MIC：8-32µg/mL）。化合物4k还显示出对其他八种植物病原真菌的显着抗真菌活性，包括尖孢镰刀菌f.sp.niveum和melonis分枝杆菌（MIC：8-32µg/mL）。进一步讨论了初步的结构-活性关系(SARs)。此外，分子对接研究表明，螺前列腺素A衍生物锚定在琥珀酸脱氢酶（SDH）的结合位点。因此,这些化合物显示出作为基于天然化合物的手性杀真菌剂的潜力，并有望作为进一步增强结构和性质的候选物。
