Laccase is a novel target for fungicides. We previously developed a new fungicide, 4-chlorocinnamaldehyde thiosemicarbazide (PMDD-5Y), as a laccase inhibitor. The introduction of active groups of natural products into the framework of a pesticide molecular structure is an effective method for discovering active lead compounds, and it has applications in the discovery of new pesticides. In this work, PMDD-5Y was selected as a lead compound, and we designed and synthesized a series of novel sulfonyl hydrazide derivatives containing the natural product scaffold 1,2,3,4-tetrahydroquinoline. The new compounds had antifungal activities against several fungi, especially Valsa mali and Sclerotinia sclerotiorum. One compound (4bl) displayed very good in vitro activity against S. sclerotiorum and V. mali, with EC₅₀ values of 3.32 and 2.78 μg/mL, respectively. The results of an enzyme activity assay showed that 4bh had the best inhibitory activity against laccase, with an EC₅₀ value of 14.85 μg/mL. This was more active than the lead compound PMDD-5Y and the positive control cysteine. Using a molecular docking method, we studied the binding mode of the title compounds with laccase. The structural features of these new laccase inhibitors as fungicides will advance research and impact the field of discovering more potent fungicides to control diseases in agriculture.

中文翻译：

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含有 1,2,3,4-四氢喹啉支架并作为漆酶抑制剂的新型杀菌剂的设计、合成和生物活性

漆酶是杀菌剂的新靶标。我们之前开发了一种新的杀菌剂，4-氯肉桂醛氨基硫脲 (PMDD-5Y)，作为漆酶抑制剂。将天然产物的活性基团引入农药分子结构框架中，是发现活性先导化合物的有效方法，在新农药的发现中具有应用价值。本工作以PMDD-5Y为先导化合物，设计合成了一系列含有天然产物支架1,2,3,4-四氢喹啉的新型磺酰肼衍生物。新化合物对几种真菌具有抗真菌活性，尤其是Valsa mali和Sclerotinia sclerotiorum。一种化合物 ( 4bl ) 表现非常好对核盘菌和马里弧菌的体外活性，EC ₅₀值分别为 3.32 和 2.78 μg/mL。酶活性测定结果表明，4bh对漆酶的抑制活性最好，EC ₅₀值为14.85 μg/mL。这比先导化合物 PMDD-5Y 和阳性对照半胱氨酸更活跃。使用分子对接方法，我们研究了标题化合物与漆酶的结合模式。这些新型漆酶抑制剂作为杀菌剂的结构特征将推动研究并影响发现更有效的杀菌剂以控制农业疾病的领域。