Synthesis, biological evaluation, and molecular docking studies of 2-chloropyridine derivatives possessing 1,3,4-oxadiazole moiety as potential antitumor agents

Bioorg Med Chem. 2010 Nov 15;18(22):7836-41. doi: 10.1016/j.bmc.2010.09.051. Epub 2010 Sep 25.

Abstract

A series of new 2-chloropyridine derivatives possessing 1,3,4-oxadiazole moiety were synthesized. Antiproliferative assay results indicated that compounds 6o and 6u exhibited the most potent activity against gastric cancer cell SGC-7901, which was more potent than the positive control. Especially, compound 6o exhibited significant telomerase inhibitory activity (IC(50)=2.3±0.07μM), which was comparable to the positive control ethidium bromide. Docking simulation was performed to position compound 6o into the active site of telomerase (3DU6) to determine the probable binding model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use
  • Binding Sites
  • Catalytic Domain
  • Cell Line, Tumor
  • Computer Simulation
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Molecular Conformation
  • Oxadiazoles / chemical synthesis
  • Oxadiazoles / chemistry*
  • Oxadiazoles / therapeutic use
  • Protein Structure, Tertiary
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry*
  • Pyridines / therapeutic use
  • Stomach Neoplasms / drug therapy
  • Telomerase / antagonists & inhibitors
  • Telomerase / metabolism

Substances

  • 2-chloro-5-(((5-(2-hydroxy-4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)thio)methyl)pyridine
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Oxadiazoles
  • Pyridines
  • 2-chloropyridine
  • Telomerase