Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan, Shandong 250012, PR China.
Bioorg Med Chem Lett. 2013 Jun 15;23(12):3556-60. doi: 10.1016/j.bmcl.2013.04.033. Epub 2013 Apr 22.
Recently, many natural products, especially some plant-derived polyphenols have been found to exert antiviral effects against influenza virus and show inhibitory activities on neuraminidases (NAs). In our research, we took caffeic acid which contained two phenolic hydroxyl groups as the basic fragment to build a small compound library with various structures. The enzyme inhibition result indicated that some compounds exhibited moderate activities against NA and compound 15d was the best with IC50=7.2 μM and 8.5 μM against N2 and N1 NAs, respectively. The 3,4-dihydroxyphenyl group from caffeic acid was important for the activity according to the docking analysis. Besides, compound 15d was found to be a non-competitive inhibitor with Ki=11.5±0.25 μM by the kinetic study and also presented anti-influenza virus activity in chicken embryo fibroblast cells. It seemed promising to discover more potent NA inhibitors from caffeic acid derivatives to cope with influenza virus.
最近，许多天然产物，特别是一些植物来源的多酚类化合物，被发现具有抗流感病毒的作用，并对神经氨酸酶（NAs）表现出抑制活性。在我们的研究中，我们以含有两个酚羟基的咖啡酸为基本片段，构建了一个具有各种结构的小分子化合物库。酶抑制结果表明，一些化合物对 NA 表现出中等活性，化合物 15d 对 N2 和 N1 NA 的 IC50 值分别为 7.2 μM 和 8.5 μM，活性最好。根据对接分析，咖啡酸中的 3,4-二羟基苯基对于活性很重要。此外，通过动力学研究发现化合物 15d 是一种非竞争性抑制剂，Ki 值为 11.5±0.25 μM，在鸡胚成纤维细胞中也表现出抗流感病毒活性。从咖啡酸衍生物中发现更有效的 NA 抑制剂以应对流感病毒似乎很有前景。
