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

Bioorg Med Chem Lett. 2019 Sep 15;29(18):2675-2680. doi: 10.1016/j.bmcl.2019.07.028. Epub 2019 Jul 19.

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.

Keywords: 3-O-β-chacotriosyl ursolic acid; Entry inhibitors; Hemagglutinin; Influenza viruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Amines / chemistry
  • Amines / pharmacology*
  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / 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
  • Triterpenes / pharmacology*
  • Ursolic Acid
  • Virus Internalization / drug effects

Substances

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