Synthesis, structural elucidation and bioevaluation of 4-amino-1,2,4-triazole-3-thione's Schiff base derivatives

Arch Pharm Res. 2016 Feb;39(2):161-171. doi: 10.1007/s12272-015-0688-2. Epub 2015 Nov 25.

Abstract

In this study, a series of ten triazole Schiff base derivatives 6a-j were synthesized through microwave assisted imine formation by reacting substituted amino triazole 5 with different substituted aldehydes. All the synthesized compounds were evaluated for their inhibitory activity against mushroom tyrosinase. Two of the compounds 6a and 6b among the series 6a-j were found to be highly potent tyrosinase inhibitors with IC50 values of 10.09 ± 1.03 and 6.23 ± 0.85 µM, respectively, which were even higher than that of the reference inhibitor kojic acid (IC50 = 16.6 ± 2.8 µM). Compounds 6e and 6f with IC50 values of 20.27 ± 2.78 and 26.02 ± 4.14 µM, respectively, were comparable to the reference inhibitor, and the remaining compounds had a moderate inhibitory activity against mushroom tyrosinase. The most potent compounds (6a, 6b) were used in the kinetic and optical analyses. The inhibition kinetics analyzed with Lineweaver-Burk plots revealed that both compounds 6a and 6b were non-competitive inhibitors of tyrosinase with inhibition constant values of 0.023 and 0.022 mM, respectively.

Keywords: Inhibitors; Kinetic analysis; Non-competitive; Tyrosinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agaricales / enzymology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Kinetics
  • Models, Chemical
  • Molecular Structure
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Monophenol Monooxygenase / metabolism
  • Schiff Bases
  • Structure-Activity Relationship
  • Thiones / chemical synthesis*
  • Thiones / pharmacology*
  • Triazoles / chemical synthesis*
  • Triazoles / pharmacology*

Substances

  • Enzyme Inhibitors
  • Schiff Bases
  • Thiones
  • Triazoles
  • Monophenol Monooxygenase
  • 4-amino-1,2,4-triazole