Molecular docking studies and biological evaluation of 1,3,4-thiadiazole derivatives bearing Schiff base moieties as tyrosinase inhibitors

Bioorg Chem. 2016 Dec:69:29-36. doi: 10.1016/j.bioorg.2016.09.007. Epub 2016 Sep 20.

Abstract

1,3,4-Thiadiazole derivatives bearing Schiff base moieties were designed, synthesized, and their tyrosinase inhibitory activities were evaluated. Some compounds displayed potent tyrosinase inhibitory activities, especially, 4-(((5-mercapto-1,3,4-thiadiazol-2-yl)-imino)methyl)-2-methoxy-phenol (14) exhibited superior inhibitory effect to the other compounds with an IC50 value of 0.036μM. The structure-activity relationships (SARs) were preliminarily discussed and docking studies showed compound 14 had strong binding affinity to mushroom tyrosinase. Hydroxy might be the active groups. The inhibition kinetics study revealed that compounds (13 and 14) inhibited tyrosinase by acting as uncompetitive inhibitors. The LD50 value of the compound 14 was 5000mg/kg.

Keywords: 1,3,4-Thiadiazole derivatives; Docking studies; Inhibition kinetics; Tyrosinase inhibitory activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Docking Simulation*
  • Molecular Structure
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Monophenol Monooxygenase / metabolism
  • Schiff Bases / chemical synthesis
  • Schiff Bases / chemistry
  • Schiff Bases / pharmacology
  • Structure-Activity Relationship
  • Thiadiazoles / chemical synthesis
  • Thiadiazoles / chemistry
  • Thiadiazoles / pharmacology*

Substances

  • Enzyme Inhibitors
  • Schiff Bases
  • Thiadiazoles
  • 1,3,4-thiadiazole
  • Monophenol Monooxygenase