Pharmacophore-based discovery of triaryl-substituted imidazole as new telomeric G-quadruplex ligand

Bioorg Med Chem Lett. 2011 Feb 1;21(3):1004-9. doi: 10.1016/j.bmcl.2010.12.019. Epub 2010 Dec 10.

Abstract

Discovery of potent and selective ligands for telomeric G-quadruplex DNA is a challenging work. Through a combination approach of pharmacophore model construction, model validation, database virtual screening, chemical synthesis and interaction evaluation, we discovered and confirmed triaryl-substituted imidazole TSIZ01 to be a new telomeric G-quadruplex ligand with potent binding and stabilizing activity to G-quadruplex DNA, as well as a 8.7-fold selectivity towards telomeric G-quadruplex DNA over duplex DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computational Biology
  • Drug Evaluation, Preclinical
  • Fluorescence Resonance Energy Transfer
  • G-Quadruplexes*
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry*
  • Imidazoles / pharmacology
  • Ligands
  • Models, Chemical
  • Models, Molecular
  • Software
  • Telomerase / antagonists & inhibitors
  • Telomerase / metabolism
  • Transition Temperature

Substances

  • Imidazoles
  • Ligands
  • TSIZ01 compound
  • imidazole
  • Telomerase