Synthesis and Biological Evaluation of New Thiosemicarbazone Derivative Schiff Bases as Monoamine Oxidase Inhibitory Agents

Molecules. 2017 Dec 28;23(1):60. doi: 10.3390/molecules23010060.

Abstract

Twenty-six novel thiosemicarbazone derivative B1-B26 were synthesized via condensation reactions between the corresponding thiosemicarbazides and aldehydes. The chemical characterization of the compounds was carried out by infrared (IR), mass (MS), proton and carbon nuclear magnetic resonance (¹H- and 13C-NMR) spectroscopic analyses. The compounds were investigated for their monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) inhibitory activity and most of them were more potent against MAO-A enzyme when compared with MAO-B enzyme. N-Cyclohexyl-2-[4-[(4-chlorophenyl)thio]benzylidene]hydrazine-1-carbothioamide (B24) was the most active compound against MAO-A. The enzyme kinetics study revealed that compound B24 has a reversible and competitive mode of binding. Interaction modes between compound B24 and MAO-A were clarified by docking studies. In addition, the favourable absorption, distribution, metabolism, and excretion (ADME) properties and non-toxic nature of compound B24 make this compound a promising MAO-A inhibitor.

Keywords: ADME; MAO-A; MAO-B; MTT; docking; enzyme kinetic study; thiosemicarbazone.

MeSH terms

  • 3T3 Cells
  • Animals
  • Binding Sites
  • Blood-Brain Barrier / metabolism
  • Cell Survival
  • Mice
  • Molecular Docking Simulation
  • Molecular Structure
  • Monoamine Oxidase / metabolism
  • Monoamine Oxidase Inhibitors / chemical synthesis*
  • Monoamine Oxidase Inhibitors / chemistry
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Protein Binding
  • Schiff Bases / chemical synthesis*
  • Schiff Bases / pharmacology*
  • Structure-Activity Relationship
  • Thiosemicarbazones / chemical synthesis*
  • Thiosemicarbazones / chemistry
  • Thiosemicarbazones / pharmacology*

Substances

  • Monoamine Oxidase Inhibitors
  • Schiff Bases
  • Thiosemicarbazones
  • Monoamine Oxidase