Further discovery of caffeic acid derivatives as novel influenza neuraminidase inhibitors

Bioorg Med Chem. 2013 Dec 15;21(24):7715-23. doi: 10.1016/j.bmc.2013.10.020. Epub 2013 Oct 26.

Abstract

Eight series of compounds, each series containing two to five compounds were prepared by structural modifications of a lead, which was previously discovered as a mild influenza neuraminidase (NA) inhibitor. On the basis of the biological result, a detailed structure-activity relationship (SAR) was derived and discussed. Several caffeic acid derivatives that acted as non-competitive inhibitors were close or superior to the lead and also presented good antiviral activities in cells. Besides, it was interesting to find that modifications of the lead with different strategies could result in selective inhibition against N1 or N2. The preliminary docking analysis indicated that the 150-cavity of the enzymes played an important role in the selective inhibition.

Keywords: Caffeic acid; Influenza; Inhibitor; Neuraminidase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Caffeic Acids / chemical synthesis
  • Caffeic Acids / chemistry
  • Caffeic Acids / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Influenza A Virus, H9N2 Subtype / drug effects*
  • Influenza A Virus, H9N2 Subtype / enzymology*
  • Kinetics
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Neuraminidase / antagonists & inhibitors*
  • Neuraminidase / metabolism
  • Structure-Activity Relationship

Substances

  • Antiviral Agents
  • Caffeic Acids
  • Enzyme Inhibitors
  • Neuraminidase
  • caffeic acid