Studies on Synthesis and Structure-Activity Relationship (SAR) of Derivatives of a New Natural Product from Marine Fungi as Inhibitors of Influenza Virus Neuraminidase

Marine Drugs

Jing Li¹  Dingmei Zhang³  Xun Zhu³  Zhenjian He³  Shu Liu²  Mengfeng Li³  Jiyan Pang¹ 

[1] School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China; E-Mail:;Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou 510080, China; E-Mail:;Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism, Bureau of Education, Sun Yat-sen University, Guangzhou 510080, China; E-Mails:

关键词: aromatic ether;    marine fungus;    neuraminidase inhibitor;   

DOI  :  10.3390/md9101887

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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