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

tetano

Editor, Senior Moderator
Mar Drugs. 2011;9(10):1887-901. Epub 2011 Oct 11.
Studies on Synthesis and Structure-Activity Relationship (SAR) of Derivatives of a New Natural Product from Marine Fungi as Inhibitors of Influenza Virus Neuraminidase.
Li J, Zhang D, Zhu X, He Z, Liu S, Li M, Pang J, Lin Y.
Source

School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China; E-Mail: zsulijing@163.com.
Abstract

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.

PMID:
22073001
[PubMed - in process]

http://www.ncbi.nlm.nih.gov/pubmed/22073001
 
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