2β-3,4-Unsaturated sialic acid derivatives: Synthesis optimization, and biological evaluation as Newcastle disease virus hemagglutinin-neuraminidase inhibitors

Bioorg Med Chem. 2020 Jul 15;28(14):115563. doi: 10.1016/j.bmc.2020.115563. Epub 2020 May 24.

Abstract

The optimization of the synthetic protocol to obtain the 3,4-unsaturated sialic acid derivatives, through the fine-tuning of both the Ferrier glycosylation conditions and the subsequent hydrolysis work-up, is herein reported. The accomplishment of the desired β-anomers and some selected α-ones, in pure form, led us to evaluate their specific inhibitory activity towards NDV-HN and human sialidase NEU3. Importantly, the resulting data allowed the identification, for the first time, of three active 3,4-unsaturated sialic acid analogs, showing IC50 values against NDV-HN in the micromolar range.

Keywords: Ferrier reaction; Hemagglutinin-neuraminidase; Montmorillonite; Newcastle disease virus; Sialidase inhibitor.

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Hemagglutinins / drug effects*
  • Hemagglutinins / metabolism
  • Humans
  • Molecular Structure
  • Neuraminidase / antagonists & inhibitors*
  • Neuraminidase / metabolism
  • Newcastle disease virus / drug effects*
  • Newcastle disease virus / enzymology
  • Sialic Acids / chemical synthesis
  • Sialic Acids / chemistry
  • Sialic Acids / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • Hemagglutinins
  • Sialic Acids
  • Neuraminidase