Pharmacophore Modeling, 3D-QSAR and Molecular Docking of Furanochalcones as Inhibitors of Monoamine Oxidase-B

Cent Nerv Syst Agents Med Chem. 2016;16(2):105-11. doi: 10.2174/1871524915666150319122540.

Abstract

Monoamine oxidase B inhibitors are of particular importance in the treatment of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Herein described is pharmacophore generation and atom-based 3D-QSAR analysis of previously reported furan based MAO-B inhibitors in order to get insight into their structural requirements responsible for high affinity. The best pharmacophore model generated with the five-point hypotheses of ADHRR: hydrogen bond acceptor (A), hydrogen bond donor (D), hydrophobic (H) and two aromatic rings (R1 & R2). On the basis of generated model, a statistically valid 3D-QSAR with good predictability was developed. Molecular docking of lead compound showed binding energy of -8.66 kcal/mol with a predicted inhibition constant of 0.448 μM towards MAO-B.

MeSH terms

  • Chalcones / chemistry*
  • Chalcones / metabolism
  • Furans / chemistry*
  • Furans / metabolism
  • Humans
  • Models, Molecular
  • Molecular Docking Simulation / methods*
  • Monoamine Oxidase / chemistry*
  • Monoamine Oxidase / metabolism
  • Monoamine Oxidase Inhibitors / chemistry*
  • Monoamine Oxidase Inhibitors / metabolism
  • Quantitative Structure-Activity Relationship*

Substances

  • Chalcones
  • Furans
  • Monoamine Oxidase Inhibitors
  • Monoamine Oxidase