Multivalency To Inhibit and Discriminate Hexosaminidases

Chemistry. 2017 Jul 6;23(38):9022-9025. doi: 10.1002/chem.201701756. Epub 2017 Jun 20.

Abstract

A set of multivalent polyhydroxylated acetamidoazepanes based on ethylene glycol, glucoside, or cyclodextrin scaffolds was prepared. The compounds were assessed against plant, mammalian, and therapeutically relevant hexosaminidases. Multimerization was shown to improve the inhibitory potency with synergy, and to fine tune the selectivity profile between related hexosaminidases.

Keywords: exo-N-acetyl-β-glucosaminidases; glycoclusters; glycosidases; iminosugars; multivalency.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology
  • Azepines / chemistry*
  • Azepines / pharmacology
  • Cyclodextrins / chemistry
  • Enzyme Inhibitors / metabolism
  • Ethylene Glycol / chemistry
  • Glucosides / chemistry
  • Hexosaminidases / antagonists & inhibitors*
  • Imino Sugars / chemistry*
  • Imino Sugars / pharmacology
  • Plants / metabolism

Substances

  • Anti-Bacterial Agents
  • Azepines
  • Cyclodextrins
  • Enzyme Inhibitors
  • Glucosides
  • Imino Sugars
  • Hexosaminidases
  • Ethylene Glycol