Synthesis and structural characterisation of selective non-carbohydrate-based inhibitors of bacterial sialidases

Chembiochem. 2012 Nov 5;13(16):2374-83. doi: 10.1002/cbic.201200433. Epub 2012 Oct 15.


The major human pathogen Streptococcus pneumoniae plays a key role in several disease states including septicaemia, meningitis and community-acquired pneumonia. Although vaccines against S. pneumoniae are available as prophylactics, there remains a need to identify and characterise novel chemical entities that can treat the diseases caused by this pathogen. S. pneumoniae expresses three sialidases, enzymes that cleave sialic acid from carbohydrate-based surface molecules. Two of these enzymes, NanA and NanB, have been implicated in the pathogenesis of S. pneumoniae and are considered to be validated drug targets. Here we report our studies on the synthesis and structural characterisation of novel NanB-selective inhibitors that are inspired by the β-amino-sulfonic acid family of buffers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Hymecromone / analogs & derivatives*
  • Hymecromone / chemical synthesis
  • Hymecromone / chemistry
  • Hymecromone / pharmacology
  • Models, Molecular
  • Molecular Structure
  • Neuraminidase / antagonists & inhibitors*
  • Neuraminidase / chemistry
  • Neuraminidase / metabolism
  • Streptococcus pneumoniae / enzymology*
  • Structure-Activity Relationship
  • Sulfonic Acids / chemical synthesis
  • Sulfonic Acids / chemistry
  • Sulfonic Acids / pharmacology*


  • Enzyme Inhibitors
  • Sulfonic Acids
  • Hymecromone
  • 2'-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid
  • Neuraminidase