title: Studies on synthesis and structure-activity relationship (SAR) of derivatives of a new natural product from marine fungi as inhibitors of influenza virus neuraminidase.
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.
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism, Bureau of Education, Sun Yat-sen University, Guangzhou 510080, China.|Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou 510080, China.|Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou 510080, China.
authors.forename: Dingmei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism, Bureau of Education, Sun Yat-sen University, Guangzhou 510080, China.|Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou 510080, China.|Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou 510080, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism, Bureau of Education, Sun Yat-sen University, Guangzhou 510080, China.|Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou 510080, China.|Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou 510080, China.
authors.forename: Zhenjian
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou 510080, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Liu
authors.affiliation: Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism, Bureau of Education, Sun Yat-sen University, Guangzhou 510080, China.|Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou 510080, China.|Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou 510080, China.
authors.forename: Mengfeng
authors.initials: M
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Jiyan
authors.initials: J
authors.lastname: Pang
authors.affiliation: 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.
authors.forename: Yongcheng
authors.initials: Y
authors.lastname: Lin
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D005658:Fungi / Q000737:chemistry*; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D062105:Molecular Docking Simulation; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D009439:Neuraminidase
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