Design, synthesis and biological evaluation of novel benzocoumarin derivatives as potent inhibitors of MAO-B activity

Bioorg Med Chem Lett. 2024 Nov 15:113:129984. doi: 10.1016/j.bmcl.2024.129984. Epub 2024 Oct 9.

Abstract

The continued research of novel reversible inhibitors targeting monoamine oxidase (MAO) B remains crucial for effectively symptomatic treatment of Parkinson's disease. In this study we synthesized and evaluated a new series of 3-aryl benzo[g] and benzo[h] coumarin derivatives as MAO-B inhibitors. Compound A6 has been found to display the most potent inhibitory activity and selectivity against the MAO-B isoform (IC50 = 13 nM and SI = >7693.31 respectively). Inhibition mode of A6 on MAO-B was predicted as mixed reversible inhibition with a Ki value of 3.274 nM. Furthermore, in order to elaborate structure-activity relationships, the binding mode of A6 was investigated by molecular docking simulations.

Keywords: Benzo[g]coumarin; Benzo[h]coumarin; Molecular docking; Monoamine oxidase; Parkinson’s Disease.

MeSH terms

  • Coumarins* / chemical synthesis
  • Coumarins* / chemistry
  • Coumarins* / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Humans
  • Molecular Docking Simulation*
  • Molecular Structure
  • Monoamine Oxidase Inhibitors* / chemical synthesis
  • Monoamine Oxidase Inhibitors* / chemistry
  • Monoamine Oxidase Inhibitors* / pharmacology
  • Monoamine Oxidase* / metabolism
  • Structure-Activity Relationship

Substances

  • Monoamine Oxidase Inhibitors
  • Monoamine Oxidase
  • Coumarins