Iminosugars as a new class of cholinesterase inhibitors

Bioorg Med Chem Lett. 2015 Feb 15;25(4):830-3. doi: 10.1016/j.bmcl.2014.12.071. Epub 2014 Dec 30.

Abstract

To further extend the scope of iminosugar biological activity, a systematic structure-activity relationship investigation has been performed by synthesizing and evaluating as cholinesterase inhibitors a library of twenty-three iminoalditols with different substitutions and stereochemistry patterns. These compounds have been evaluated in vitro for the inhibition of cholinesterases (different sources of acetylcholinesterase and butyrylcholinesterase). Some compounds have IC50 values in the micromolar range and display significant inhibition selectivity for butyrylcholinesterase over acetylcholinesterase. These are the first examples of iminosugar-based inhibitors of cholinesterases.

Keywords: Alzheimer disease; Cholinesterases; Iminosugars; Inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / pharmacology
  • Imino Sugars / chemistry*
  • Imino Sugars / pharmacology*
  • Structure-Activity Relationship

Substances

  • Cholinesterase Inhibitors
  • Imino Sugars