Synthesis and evaluation of quinoxaline derivatives as potential influenza NS1A protein inhibitors

Bioorg Med Chem Lett. 2011 May 15;21(10):3007-11. doi: 10.1016/j.bmcl.2011.03.042. Epub 2011 Mar 17.

Abstract

A library of quinoxaline derivatives were prepared to target non-structural protein 1 of influenza A (NS1A) as a means to develop anti-influenza drug leads. An in vitro fluorescence polarization assay demonstrated that these compounds disrupted the dsRNA-NS1A interaction to varying extents. Changes of substituent at positions 2, 3 and 6 on the quinoxaline ring led to variance in responses. The most active compounds (35 and 44) had IC(50) values in the range of low micromolar concentration without exhibiting significant dsRNA intercalation. Compound 44 was able to inhibit influenza A/Udorn/72 virus growth.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Activation / drug effects*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Nuclear Proteins / antagonists & inhibitors*
  • Quinoxalines / chemical synthesis*
  • Quinoxalines / chemistry
  • Quinoxalines / pharmacology*
  • RNA-Binding Proteins
  • Structure-Activity Relationship
  • Transcription Factors / antagonists & inhibitors*
  • Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

  • Enzyme Inhibitors
  • IVNS1ABP protein, human
  • Nuclear Proteins
  • Quinoxalines
  • RNA-Binding Proteins
  • Transcription Factors
  • Viral Nonstructural Proteins