Identification of novel monoamine oxidase selective inhibitors employing a hierarchical ligand-based virtual screening strategy

Future Med Chem. 2019 Apr;11(8):801-816. doi: 10.4155/fmc-2018-0596.

Abstract

Aim: Due to the pivotal role in the oxidative deamination of monoamine neurotransmitters, two distinct monoamine oxidase (MAO) subtypes, MAO-A and MAO-B, present a significant pharmacological interest. Here, we reported a hierarchical and time-efficient ligand-based virtual screening strategy to identify potent selective and reversible MAO inhibitors. Result: A total of 130 compounds were assessed in dose-response biochemical assay against MAOs. Among them, 70 compounds were active with inhibition higher than 70%, involving 25 compounds with IC50 values less than 1 μM. Conclusion: Our research demonstrated the validity of Biologically Relevant Spectrum (BRS-3D) in predicting subtype-selective ligands and afforded a novel highly efficient way to develop selective inhibitors in the early stage of drug discovery.

Keywords: BRS-3D; monoamine oxidase selective inhibitors; virtual screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Design
  • Drug Discovery*
  • Humans
  • Inhibitory Concentration 50
  • Ligands
  • Molecular Docking Simulation
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors / chemistry*
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Ligands
  • Monoamine Oxidase Inhibitors
  • Monoamine Oxidase