1-N-substituted thiocarbamoyl-3-phenyl-5-thienyl-2-pyrazolines: synthesis and evaluation as MAO inhibitors

Arch Pharm (Weinheim). 2003 Aug;336(8):362-71. doi: 10.1002/ardp.200300732.

Abstract

Twelve new 1-N-substituted thiocarbomoyl-3-phenyl-5-thienyl-2-pyrazoline derivatives were synthesized and evaluated their for antidepressant, anxiogenic and mammalian monoamine oxidase (MAO)-A and Binhibitory activities by in vivo and in vitro tests. MAO was isolated and purified from the mitochondrial pellet of bovine liver homogenates and human platelets. All of the new compounds inhibited the total MAO activity of liver homogenates and the inhibition was found to be time-dependent. Four compounds (3 i-3 l) inhibited MAO-B selectively and irreversibly in a classical non-competitive manner with IC(50) values in the range of 22.00-91.50 microM. The rest of the compounds appeared to be non-selective reversible inhibitors. It was suggested that the p-methoxy group on the phenyl ring in the compounds increased the inhibitory effect and selectivity toward MAO-B. The reversible and unselective inhibition of MAO by the remaining compounds was suggested to be related to their properties of acting ability to act as both as substrate and inhibitor at the same time. However, none of the novel compounds showed antidepressant activity as expected suggesting formation of inactive metabolites. We conclude that the compounds appeared as which functioned as selective MAO-B inhibitors might have promising features as therapeutic properties in the treatment of Parkinson disease. In vivo studies are needed to verify this hypothesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Platelets / enzymology
  • Cattle
  • Female
  • Humans
  • In Vitro Techniques
  • Indicators and Reagents
  • Liver / enzymology
  • Magnetic Resonance Spectroscopy
  • Male
  • Mice
  • Monoamine Oxidase Inhibitors / chemical synthesis*
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / pharmacology*
  • Substrate Specificity
  • Thiocarbamates / chemical synthesis*
  • Thiocarbamates / pharmacology*

Substances

  • Indicators and Reagents
  • Monoamine Oxidase Inhibitors
  • Pyrazoles
  • Thiocarbamates