2. Academic Validation
  3. Iminosugars as a new class of cholinesterase inhibitors

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.
Camille Decroocq 1,  Fabien Stauffert 1,  Olivier Pamlard 2,  Farah Oulaïdi 3,  Estelle Gallienne 3,  Olivier R Martin 3,  Catherine Guillou 4,  Philippe Compain 5
Affiliations

Affiliations

  • 1 Laboratoire de Synthèse Organique et Molécules Bioactives, Université de Strasbourg/CNRS (UMR 7509), Ecole Européenne de Chimie, Polymères et Matériaux, 25 rue Becquerel, 67087 Strasbourg, France.
  • 2 ICSN-CNRS (Bat. 27)-LabEx LERMIT, 1, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.
  • 3 ICOA, UMR 7311, Université d'Orléans et CNRS, rue de Chartres, BP 6759, 45067 Orléans, France.
  • 4 ICSN-CNRS (Bat. 27)-LabEx LERMIT, 1, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France. Electronic address: [email protected].
  • 5 Laboratoire de Synthèse Organique et Molécules Bioactives, Université de Strasbourg/CNRS (UMR 7509), Ecole Européenne de Chimie, Polymères et Matériaux, 25 rue Becquerel, 67087 Strasbourg, France; Institut Universitaire de France, 103 Bd Saint-Michel, 75005 Paris, France. Electronic address: [email protected].
PMID: 25597004 DOI: 10.1016/j.bmcl.2014.12.071
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.

Figures
Products