Design, synthesis, and biological evaluation of human sialidase inhibitors. Part 1: selective inhibitors of lysosomal sialidase (NEU1)

Bioorg Med Chem Lett. 2008 Jan 15;18(2):532-7. doi: 10.1016/j.bmcl.2007.11.084. Epub 2007 Nov 28.

Abstract

We here report the design and synthesis of selective human lysosomal sialidase (NEU1) inhibitors. A series of amide-linked C9 modified DANA (2-deoxy-2,3-dehydro-N-acetylneuraminic acid) analogues were synthesized and their inhibitory activities against all four human sialidases (NEU1-NEU4) were determined. Structure-based approach was used to investigate the basis of selectivity of the compounds with experimentally observed activity. Results from the present study are found to be informative in a qualitative manner for the further design of isoform selective human sialidase inhibitors for therapeutic value.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Hydrogen Bonding
  • Lysosomes / enzymology*
  • Models, Molecular
  • Molecular Structure
  • Neuraminidase / antagonists & inhibitors*

Substances

  • Enzyme Inhibitors
  • Neuraminidase