Exploration of new scaffolds as potential MAO-A inhibitors using pharmacophore and 3D-QSAR based in silico screening

Bioorg Med Chem Lett. 2011 Apr 15;21(8):2419-24. doi: 10.1016/j.bmcl.2011.02.072. Epub 2011 Feb 19.

Abstract

Monoamine oxidase-A (MAO-A) inhibitors are of particular importance in the treatment of depressive disorders. Herein described is pharmacophore generation and atom-based 3D-QSAR analysis of previously reported pyrrole based MAO-A inhibitors in order to get insight into their structural requirements responsible for high affinity. The best pharmacophore model generated consisted of four features DHHR: a hydrogen bond donor (D), two hydrophobic groups (H) and an aromatic ring (R). Based on model generated, a statistically valid 3D-QSAR with good predictability was developed. Derived pharmacophore was used as a query to search Zinc 'clean drug-like' database. Hits retrieved were passed progressively through filters like fitness score, predicted activity and docking scores. The survived hits present new scaffolds with a potential for MAO-A inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Catalytic Domain
  • Computer Simulation
  • Databases, Factual
  • Monoamine Oxidase / chemistry*
  • Monoamine Oxidase / metabolism
  • Monoamine Oxidase Inhibitors / chemical synthesis
  • Monoamine Oxidase Inhibitors / chemistry*
  • Monoamine Oxidase Inhibitors / pharmacology
  • Quantitative Structure-Activity Relationship

Substances

  • Monoamine Oxidase Inhibitors
  • Monoamine Oxidase