In silico to in vitro screening of hydroxypyridinones as acetylcholinesterase inhibitors

Bioorg Med Chem Lett. 2016 Mar 15;26(6):1624-1628. doi: 10.1016/j.bmcl.2016.01.080. Epub 2016 Feb 1.

Abstract

We have previously shown the improved acetylcholinesterase inhibitory activity of a model hydroxypyridinone compound transforming the hydroxyl group on the main ring into an N,N-dimethylcarbamate group; in the course of that study we developed a computational model to screen compounds for enzymatic activity. Herein we report development of second generation libraries. Candidates that adhere to drug-like criteria from a virtual library of compounds were tested using computational docking studies. Synthesis and characterization of chosen test compounds and their acetylcholinesterase inhibitory activity are presented.

Keywords: Acetylcholinesterase; Dimethylcarbamate; Hydroxypyridinone; Inhibitor; Virtual library screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • In Vitro Techniques
  • Molecular Docking Simulation*
  • Molecular Structure
  • Pyridones / chemical synthesis
  • Pyridones / chemistry*
  • Pyridones / pharmacology*
  • Structure-Activity Relationship

Substances

  • Cholinesterase Inhibitors
  • Pyridones
  • Acetylcholinesterase