Synthesis, thymidine phosphorylase inhibition and molecular modeling studies of 1,3,4-oxadiazole-2-thione derivatives

Bioorg Chem. 2015 Jun:60:37-41. doi: 10.1016/j.bioorg.2015.04.003. Epub 2015 Apr 20.

Abstract

Thymidine phosphorylase (TP) inhibitors have attracted great attention due to their ability to suppress the tumors formation. In our ongoing research, a series of 1,3,4-oxadiazole-2-thione (1-12) has been synthesized under simple reaction conditions in good to excellent yields (86-98%) and their TP inhibition potential has also been evaluated. The majority of synthesized compounds showed moderate thymidine phosphorylase inhibitory activity with IC50 values ranging from 38.24±1.28 to 258.43±0.43μM, and 7-deazaxanthine (7DX) was used as a reference compound (IC50 38.68±4.42). The TP activity was very much dependent on the C-5 substituents; among this series the compound 6 bearing 4-hydroxyphenyl group was found to be the most active with IC50 38.24±1.28μM. Molecular docking studies revealed their binding mode.

Keywords: Anti-cancer; Molecular modeling; Oxadiazole-2-thione; Thymidine phosphorylase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Escherichia coli / drug effects
  • Escherichia coli / enzymology
  • Humans
  • Inhibitory Concentration 50
  • Molecular Docking Simulation
  • Oxadiazoles / chemical synthesis
  • Oxadiazoles / chemistry*
  • Oxadiazoles / pharmacology*
  • Thiones / chemical synthesis
  • Thiones / chemistry
  • Thiones / pharmacology
  • Thymidine Phosphorylase / antagonists & inhibitors*
  • Thymidine Phosphorylase / metabolism

Substances

  • Enzyme Inhibitors
  • Oxadiazoles
  • Thiones
  • 1,3,4-oxadiazole
  • Thymidine Phosphorylase