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Research Article

抗甲型流感病毒2-脲烟酰胺衍生物的设计、合成及生物活性研究

卷 29, 期 26, 2022

发表于: 17 May, 2022

页: [4610 - 4627] 页: 18

弟呕挨: 10.2174/0929867329666220224114627

价格: $65

摘要

背景:病毒对现有抑制剂的耐药性和神经氨酸酶抑制剂的时效性限制了可用于预防和治疗严重流感感染的抗病毒药物的数量。因此，迫切需要开发预防和治疗流感感染的新药。 目的:设计合成新型2-脲烟酰胺衍生物，并评价其抗鸡病毒性肝炎病毒的活性。此外，我们预测了这些化合物对PA-PB1亚基的抑制能力，并预测了这些化合物与RNA聚合酶蛋白（PDB ID 3CM8）的对接姿态。 方法:采用经典的有机化学方法合成新设计的化合物，并对其抑制RNP和抗甲型流感病毒的能力进行体外测试。此外，将合成的23个分子对产生的药效团Hypo1进行作用，预测RNA聚合酶的活性靶标PA-PB1亚基。使用Discovery Studio 2016中的ADMET模块计算ADMET药代动力学参数。对接结果帮助我们展示了这些化合物与3CM8之间可能的相互作用。 结果:合成的2-脲烟酰胺衍生物具有较强的抗流感抑制作用。目标化合物7b和7c具有明显的抗病毒活性，有望成为新型抗病毒抑制剂先导化合物。此外，根据预测结果和对接结果，化合物7b显示了良好的ADME特性，可能是一种针对PA-PB1亚基的RNA聚合酶抑制剂。 结论:该研究揭示了一系列新的化合物，可能有助于寻找一种有效的药物对抗流感病毒。

关键词: 流感病毒，RNA依赖的RNA聚合酶，2-脲烟酰胺衍生物，抗病毒抑制剂，PA-PB1亚基，RNP活性抑制。

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