Synthesis and biological evaluation of novel oxadiazole derivatives: a new class of thymidine phosphorylase inhibitors as potential anti-tumor agents

Bioorg Med Chem. 2014 Feb 1;22(3):1008-15. doi: 10.1016/j.bmc.2013.12.043. Epub 2013 Dec 30.


Based on the fact that the thymidine phosphorylase inhibitors are considered potential anti-tumor agents, a range of novel oxadiazole derivatives 3a-3u was designed and synthesized by a simple and facile synthetic route. The biological assay revealed that majority of compounds displayed modest inhibitory activity against thymidine phosphorylase at low micromolar concentrations (IC50 173.23±3.04 to 14.40±2.45μM). In the current study the most active compounds were 3h and 3q with IC50 values 14.40±2.45 and 17.60±1.07μM, respectively. Molecular docking studies were performed on the most active compounds (3h, 3k, 3o-3q) to show their binding mode.

Keywords: 1,3,4-Oxadiazole-2-thione; Angiogenesis; Anti-cancer activity; Mannich bases; Thymidine phosphorylase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Chemistry Techniques, Synthetic
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Hydrogen Bonding
  • Inhibitory Concentration 50
  • Molecular Docking Simulation
  • Molecular Structure
  • Oxadiazoles / chemical synthesis
  • Oxadiazoles / chemistry*
  • Oxadiazoles / pharmacology*
  • Structure-Activity Relationship
  • Thymidine Phosphorylase / antagonists & inhibitors*


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Oxadiazoles
  • Thymidine Phosphorylase