Design of N-acetyl-6-sulfo-beta-d-glucosaminide-based inhibitors of influenza virus sialidase

Bioorg Med Chem. 2004 Mar 15;12(6):1367-75. doi: 10.1016/j.bmc.2004.01.013.

Abstract

Biological activity of N-acetyl-6-sulfo-beta-d-glucosaminides (6-sulfo-GlcNAc 1) having a structural homology to N-acetylneuraminic acid (Neu5Ac 2) and 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (Neu5Ac2en 3) was examined in terms of inhibitory activity against influenza virus sialidase (influenza, A/Memphis/1/71 H3N2). pNP 6-Sulfo-GlcNAc 1a was proved to show substantial activity to inhibit the virus sialidase (IC(50)=2.8 mM), though p-nitrophenyl (pNP) GlcNAc without 6-sulfo group and pNP 6-sulfo-GlcNH(3)(+) 1b without 2-NHAc showed little activity (IC(50) >50 mM). The activity was enhanced nearly 100-fold when the pNP group of 1a was converted to p-acetamidophenyl one 5 (IC(50)=30 microM) or replaced with 1-naphthyl 6 (IC(50)=10 microM) or n-propyl one 8 (IC(50)=11 microM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Glucosamine / analogs & derivatives*
  • Glucosamine / chemistry*
  • Influenza A virus / drug effects*
  • Influenza A virus / enzymology
  • Influenza A virus / growth & development
  • Neuraminidase / antagonists & inhibitors*
  • Sialic Acids / chemistry
  • Sialic Acids / pharmacology
  • Structure-Activity Relationship

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • Sialic Acids
  • glucosaminic acid
  • Neuraminidase
  • Glucosamine