Molecular dynamics, flexible docking, virtual screening, ADMET predictions, and molecular interaction field studies to design novel potential MAO-B inhibitors

J Biomol Struct Dyn. 2008 Feb;25(4):347-55. doi: 10.1080/07391102.2008.10507183.

Abstract

Monoamine oxidase is a flavoenzyme bound to the mitochondrial outer membranes of the cells, which is responsible for the oxidative deamination of neurotransmitter and dietary amines. It has two distinct isozymic forms, designated MAO-A and MAO-B, each displaying different substrate and inhibitor specificities. They are the well-known targets for antidepressant, Parkinson's disease, and neuroprotective drugs. Elucidation of the x-ray crystallographic structure of MAO-B has opened the way for the molecular modeling studies. In this work we have used molecular modeling, density functional theory with correlation, virtual screening, flexible docking, molecular dynamics, ADMET predictions, and molecular interaction field studies in order to design new molecules with potential higher selectivity and enzymatic inhibitory activity over MAO-B.

MeSH terms

  • Computer Simulation*
  • Drug Design*
  • Drug Interactions
  • Humans
  • Indans / chemistry
  • Indans / pharmacology
  • Isoenzymes / chemistry
  • Isoenzymes / metabolism
  • Models, Molecular*
  • Monoamine Oxidase / chemistry*
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors / chemical synthesis*
  • Monoamine Oxidase Inhibitors / pharmacology
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology
  • Picolinic Acids / chemistry
  • Picolinic Acids / pharmacology
  • Thermodynamics*

Substances

  • Indans
  • Isoenzymes
  • Monoamine Oxidase Inhibitors
  • Neuroprotective Agents
  • Picolinic Acids
  • rasagiline
  • lazabemide
  • Monoamine Oxidase