Wang Fei-Yu, Xu Dan, He Hong-Wei, Lin Guo-Tai, Zhou Huan, Liu Xili, Xu Gong
Key Laboratory of Plant Protection Resources and Pest Management of Ministry of Education, Key Laboratory of Integrated Pest Management on the Loess Plateau of Ministry of Agriculture and Rural Affairs, College of Plant Protection, Northwest A&F University, Yangling 712100 Shaanxi, China.
Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100 Shaanxi, China.
J Agric Food Chem. 2025 Apr 23;73(16):9521-9532. doi: 10.1021/acs.jafc.4c11005. Epub 2025 Apr 10.
To discover novel fungicides with unique structures, a series of α-methylene-γ-butyrolactone derivatives were designed and synthesized by incorporating a flexible amide or hydrazide chain through active substructure splicing and linker modification strategies. Bioassay assessments demonstrated that certain hydrazide-containing compounds have potent fungicidal efficacy. Notably, compound exhibited broad-spectrum antifungal activity, with EC values as low as 0.179, 0.301, 0.647, 0.549, and 0.789 mg/L against , , , and , respectively. experiments confirmed the effective fungicidal activity of compound , showing an inhibitory rate of 69.7% against on apple twigs at 200 mg/L. Additionally, at a concentration of 100 mg/L, compound demonstrated significant protective and curative effects against on rice plants. Research on the mechanism of action revealed that compound could disrupt hyphal morphology, induce reactive oxygen species (ROS) accumulation, affect mitochondrial membrane potential (MMP), and interfere with respiratory metabolism by binding to complex II. Molecular docking analysis showed significant interactions of compound with TRP 173, TYR 58, and ARG 43 in the succinate dehydrogenase (SDH) binding site, resembling the binding mode of . These findings suggest that compound holds potential as an SDH inhibitor for agricultural disease control.
为了发现具有独特结构的新型杀菌剂，通过活性亚结构拼接和连接基修饰策略，引入柔性酰胺或酰肼链，设计并合成了一系列α-亚甲基-γ-丁内酯衍生物。生物活性测定表明，某些含酰肼的化合物具有很强的杀菌效果。值得注意的是，化合物对、、、和分别表现出广谱抗真菌活性，其EC值低至0.179、0.301、0.647、0.549和0.789mg/L。实验证实了化合物的有效杀菌活性，在200mg/L时对苹果枝条上的抑制率为69.7%。此外，在100mg/L的浓度下，化合物对水稻植株上的表现出显著的保护和治疗效果。作用机制研究表明，化合物可破坏菌丝形态，诱导活性氧（ROS）积累，影响线粒体膜电位（MMP），并通过与复合物II结合干扰呼吸代谢。分子对接分析表明，化合物与琥珀酸脱氢酶（SDH）结合位点中的TRP 173、TYR 58和ARG 43有显著相互作用，类似于的结合模式。这些发现表明，化合物作为一种用于农业病害防治的SDH抑制剂具有潜力。
