In order to screen novel fungicide leads, 19 pyrrolidine-2,4-dione derivatives containing the pharmacophores of both hydrazine and diphenyl ether were designed, synthesized, and characterized by FT-IR, ¹H NMR, ¹³C NMR, and HR-MS. The obtained target compounds were evaluated for their antifungal activity against Rhizoctonia solani (Rs), Botrytis cinerea (Bc), and Fusarium graminearum (Fg). The bioassay results indicated that the majority of the target compounds exhibited striking biological activities against the above-mentioned fungi. Strikingly, target compound 4h obviously inhibited the growth of Rs in vitro with an EC₅₀ value of 0.39 μg mL⁻¹, which was better than the commercialized fungicide boscalid (2.21 μg mL⁻¹). Subsequently, 4h was further evaluated for the in vivo anti-Rs effect on rice leaves, affording a control efficiency of 45.33% at 200 μg mL⁻¹. Scanning electron microscopy (SEM) was used for observing the changes in the mycelium morphology. Numerous abnormal branches and swellings were found on the hyphae that were treated with 4h. Based on the bioassay results against Rs, a comparative molecular similarity index analysis model was formulated to further analyze the quantitative structure–activity relationship (QSAR) of the target compounds. The above 3D-QSAR analyses revealed that introducing hydrophobic 4-FPh, 4-ClPh, or 4-BrPh fragments at the R² position could considerably increase the antifungal activity against Rs.

中文翻译：

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含有肼和二苯醚药效基团作为潜在抗真菌剂的新型吡咯烷-2,4-二酮衍生物：设计，合成，生物学评估和3D-QSAR研究

为了筛选新型杀菌剂，设计，合成了19种同时含有肼和二苯醚药效基团的吡咯烷-2,4-二酮衍生物，并通过FT-IR，¹ H NMR，¹³ C NMR和HR-MS进行了表征。。评价所获得的目标化合物对茄属根瘤菌（Rs），灰葡萄孢菌（Bc）和禾谷镰刀菌（Fg）的抗真菌活性。生物测定结果表明，大多数目标化合物对上述真菌表现出惊人的生物学活性。令人惊讶的是，目标化合物4h明显抑制了体外Rs的EC ₅₀值为0.39μgmL ^-1，比商品化杀菌剂Boscalid（2.21μgmL ^-1）更好。随后，进一步评估4h对稻叶的体内抗Rs作用，在200μgmL ^-1下提供45.33％的控制效率。扫描电子显微镜（SEM）用于观察菌丝体形态的变化。用4h处理的菌丝上有许多异常的分支和肿胀。基于针对Rs的生物测定结果，建立了比较分子相似性指数分析模型，以进一步分析目标化合物的定量构效关系（QSAR）。上述3D-QSAR分析表明，在R ²位置引入疏水的4-FPh，4-ClPh或4-BrPh片段可以大大提高对Rs的抗真菌活性。