Xanthones from Polygala karensium inhibit neuraminidases from influenza A viruses

Bioorg Med Chem Lett. 2012 Jun 1;22(11):3688-92. doi: 10.1016/j.bmcl.2012.04.028. Epub 2012 Apr 12.

Abstract

The emergence of the H1N1 swine flu pandemic has the possibility to develop the occurrence of disaster- or drug-resistant viruses by additional reassortments in novel influenza A virus. In the course of an anti-influenza screening program for natural products, 10 xanthone derivatives (1-10) were isolated by bioassay-guided fractionation from the EtOAc-soluble extract of Polygala karensium. Compounds 1, 3, 5, 7, and 9 with a hydroxy group at C-1 showed strong inhibitory effects on neuraminidases from various influenza viral strains, H1N1, H9N2, novel H1N1 (WT), and oseltamivir-resistant novel H1N1 (H274Y) expressed in 293T cells. In addition, these compounds reduced the cytopathic effect of H1N1 swine influenza virus in MDCK cells. Our results suggest that xanthones from P. karensium may be useful in the prevention and treatment of disease by influenza viruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemistry*
  • Antiviral Agents / isolation & purification
  • Antiviral Agents / pharmacology
  • Cell Line
  • Dogs
  • Drug Resistance, Viral
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology
  • HEK293 Cells
  • Humans
  • Influenza A Virus, H1N1 Subtype / drug effects
  • Influenza A Virus, H1N1 Subtype / enzymology
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza A Virus, H9N2 Subtype / drug effects
  • Influenza A Virus, H9N2 Subtype / enzymology
  • Influenza A virus / drug effects
  • Influenza A virus / enzymology*
  • Kinetics
  • Mutation
  • Neuraminidase / antagonists & inhibitors*
  • Neuraminidase / metabolism
  • Oseltamivir / pharmacology
  • Polygala / chemistry*
  • Structure-Activity Relationship
  • Xanthones / chemistry*
  • Xanthones / isolation & purification
  • Xanthones / pharmacology

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • Xanthones
  • Oseltamivir
  • Neuraminidase