Novel 2,5-disubstituted-1,3,4-oxadiazole derivatives as MAO-B inhibitors: Synthesis, biological evaluation and molecular modeling studies

Bioorg Chem. 2021 Jul:112:104917. doi: 10.1016/j.bioorg.2021.104917. Epub 2021 Apr 16.

Abstract

Thirty novel 2,5-disubstituted-1,3,4-oxadiazole derivatives bearing urea moiety were designed and synthesized. IR, 1H-NMR, 13C-NMR and mass spectroscopic methods and elemental analysis were used to confirm the structures of the compounds. Their monoamine oxidase inhibitory activity was determined against the MAO-A and MAO-B isoforms. None of the compounds showed the potent MAO-A inhibitory activity, while the MAO-B inhibition was significantly found in the range of 62 to 98%. Among them, the compounds H8, H9 and H12 bearing chloro substituent at the fourth position of phenylurea were found to show potent monoamine oxidase B inhibitory activity with IC50 values 0.039-0.066 µM. To define and evaluate the interaction mechanism between compound H8 and monoamine oxidase B, molecular docking studies have been made.

Keywords: 1,3,4-oxadiazole; MAO inhibitors; Molecular docking; Urea derivatives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors / chemical synthesis
  • Monoamine Oxidase Inhibitors / chemistry
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Oxadiazoles / chemical synthesis
  • Oxadiazoles / chemistry
  • Oxadiazoles / pharmacology*
  • Structure-Activity Relationship

Substances

  • Monoamine Oxidase Inhibitors
  • Oxadiazoles
  • 1,3,4-oxadiazole
  • Monoamine Oxidase