School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China.
Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism, Bureau of Education, Sun Yat-sen University, Guangzhou 510080, China.
Mar Drugs. 2011;9(10):1887-1901. doi: 10.3390/md9101887. Epub 2011 Oct 11.
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 IC(50) 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.
基于来源于红树林真菌的天然异戊烯基苯醚，合成了 32 个类似物，并评价了它们对甲型 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/广东 SB/01/2009（H1N1）、A/广东/03/2009（H1N1）和 A/广东/05/2009（H1N1）的 IC50 值分别为 26.96 μM、27.73 μM 和 25.13 μM，均强于苯甲酸衍生物（~mM 级）。这些是一类新型的非氮芳香醚神经氨酸酶（NA）抑制剂。它们的结构简单，合成路线不复杂。构效关系（SAR）分析表明，芳基醛和未取代的羟基对 NA 抑制活性很重要。进行了分子对接研究以解释化合物的 SAR，并为进一步的结构修饰提供了有价值的信息。
