Design, synthesis, monoamine oxidase inhibition and docking studies of new dithiocarbamate derivatives bearing benzylamine moiety

Bioorg Chem. 2018 Feb;76:177-187. doi: 10.1016/j.bioorg.2017.11.012. Epub 2017 Nov 20.

Abstract

A new series of thirteen 2-[(4-fluorophenyl)(4-nitrobenzyl)amino]-2-oxoethyl-1-substituted-carbodithioate derivatives (4a-4m) were synthesized and tested for their human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitory potential by an in vitro fluorometric method. Most of the compounds have found to be selective towards MAO-B than MAO-A. Compound 4j that carrying 4-nitrophenyl piperazine moiety, was detected as the most active agent amongst all compounds with the IC50 value of 0.097 ± 0.003 µM for MAO-B while that of selegiline was 0.040 ± 0.002 µM. The enzyme kinetic study reported that compound 4j is a reversible and non-competitive inhibitor. Interaction modes between the hMAO-B and compound 4j were determined by docking studies. The study also revealed that compound 4j has the highest binding scores. Besides, compound 4j has not cytotoxicity at its effective concentration against hMAO-B.

Keywords: Amplex red; Arylalkyl amine moiety; Human monoamine oxidase; Molecular docking.

MeSH terms

  • Animals
  • Benzylamines / chemical synthesis
  • Benzylamines / chemistry*
  • Benzylamines / toxicity
  • Drug Design*
  • Enzyme Assays
  • Humans
  • Kinetics
  • Mice
  • Molecular Docking Simulation
  • Monoamine Oxidase / chemistry
  • Monoamine Oxidase Inhibitors / chemical synthesis
  • Monoamine Oxidase Inhibitors / chemistry*
  • Monoamine Oxidase Inhibitors / toxicity
  • NIH 3T3 Cells
  • Thiocarbamates / chemical synthesis
  • Thiocarbamates / chemistry*
  • Thiocarbamates / toxicity

Substances

  • Benzylamines
  • Monoamine Oxidase Inhibitors
  • Thiocarbamates
  • Monoamine Oxidase