Studies on Synthesis and Structure-Activity Relationship (SAR) of Derivatives of a New Natural Product from Marine Fungi as Inhibitors of Influenza Virus Neuraminidase
Studies on Synthesis and Structure-Activity Relationship (SAR) of Derivatives of a New Natural Product from Marine Fungi as Inhibitors of Influenza Virus Neuraminidase
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新型海洋真菌天然产物流感病毒神经氨酸酶抑制剂的合成及构效关系（SAR）研究
DOI：
10.3390/md9101887
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发表时间：
2011-10-01
期刊：
影响因子：
5.4
通讯作者：
Lin, Yongcheng
中科院分区：
文献类型：
--
作者：
Li, Jing;Zhang, Dingmei;Lin, Yongcheng
基于来自红树林衍生真菌的天然异戊二烯基苯基醚，合成了32个类似物，并评价了其对H1N1流感神经氨酸酶的抑制活性。化合物15（3-（烯丙氧基）-4-羟基苯甲醛）表现出最强的抑制活性，对A/GuangdongSB/01/2009（H1N1）、A/Guangdong/03/2009（H1N1）和A/Guangdong/ 05/2009（H1N1）的IC 50值分别为26.96 μM、27.73 μM和25.13 μM，其强于苯甲酸衍生物（~mM水平）。这是一类新的非氮芳香醚类神经氨酸酶（NA）抑制剂。它们的结构简单，合成路线也不复杂。构效关系分析表明，芳香醛和未取代羟基对NA抑制活性有重要影响。通过分子对接的方法解释了化合物的构效关系，为进一步的结构修饰提供了有价值的信息。
Based on the natural isoprenyl phenyl ether from a mangrove-derived fungus, 32 analogues were synthesized and evaluated for inhibitory activity against influenza H1N1 neuraminidase. Compound 15 (3-(allyloxy)-4-hydroxybenzaldehyde) exhibited the most potent inhibitory activity, with IC50 values of 26.96 μM for A/GuangdongSB/01/2009 (H1N1), 27.73 μM for A/Guangdong/03/2009 (H1N1), and 25.13 μM for A/Guangdong/ 05/2009 (H1N1), respectively, which is stronger than the benzoic acid derivatives (~mM level). These are a new kind of non-nitrogenous aromatic ether Neuraminidase (NA) inhibitors. Their structures are simple and the synthesis routes are not complex. The structure-activity relationship (SAR) analysis revealed that the aryl aldehyde and unsubstituted hydroxyl were important to NA inhibitory activities. Molecular docking studies were carried out to explain the SAR of the compounds, and provided valuable information for further structure modification.