Incorporation of privileged structures into 3-O-β-chacotriosyl ursolic acid can enhance inhibiting the entry of the H5N1 virus.

Abstract

The glycoprotein hemagglutinin of influenza virus plays a key role in the initial stage of virus infection, making it a potential target for novel influenza viruses entry inhibitors. Two "privileged fragments", 2-(piperidin-1-yl)ethan-1-amine and 2-(1,3-oxazinan-3-yl)ethan-1-amine were integrated into 3-O-β-chacotriosyl ursolic acid producing new derivatives 5 and 6 with improved activity against IAVs in vitro. Mechanistically, compound 6 was effective in inhibiting infection of H1-, H3-, and H5-typed influenza A viruses by interfering with the viral hemagglutinin. Furthermore, the docking studies were in agreement with the antiviral data. These results showed that the title compound 6 as a new lead compound was meriting further optimization and development.

• Authors: Hui Li, Lizhu Chen, Sumei Li, Yixian Liao, Lei Wang, Zhihao Liu, Shuwen Liu, Gaopeng Song
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 29 Issue 18 Pg. 2675-2680 (09 15 2019) ISSN: 1464-3405 [Electronic] England
• PMID: 31371135 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• Amines
• Antiviral Agents
• Hemagglutinin Glycoproteins, Influenza Virus
• Triterpenes
• ursolic acid

Topics

• A549 Cells
• Amines (chemistry, pharmacology)
• Animals
• Antiviral Agents (chemical synthesis, chemistry, pharmacology)
• Dogs
• Dose-Response Relationship, Drug
• Hemagglutinin Glycoproteins, Influenza Virus (metabolism)
• Humans
• Influenza A Virus, H5N1 Subtype (drug effects)
• Madin Darby Canine Kidney Cells
• Microbial Sensitivity Tests
• Molecular Structure
• Structure-Activity Relationship
• Triterpenes (chemistry, pharmacology)
• Virus Internalization (drug effects)