Platinum(II) phenanthroimidazoles for targeting telomeric G-quadruplexes

ChemMedChem. 2012 Jan 2;7(1):85-94. doi: 10.1002/cmdc.201100453. Epub 2011 Nov 3.


A rationally designed progression of phenanthroimidazole platinum(II) complexes were examined for their ability to target telomere-derived intramolecular G-quadruplex DNA. Through the use of circular dichroism, fluorescence displacement assays, and molecular modeling we show that these complexes template and stabilize G-quadruplexes from sequences based on the human telomeric repeat (TTAGGG)(n). The greatest stabilization was observed for the p-chlorophenyl derivative 6((G4)DC(50) =0.31 μM). We also show that the G-quadruplex binding complexes are able to inhibit telomerase activity through a modified telomerase repeat amplification protocol (TRAP-LIG assay). Preliminary cell studies show that complex 6 is preferentially cytotoxic toward cancer over normal cell lines, indicating its potential use in cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Base Sequence
  • Cell Line
  • Cell Line, Tumor
  • Circular Dichroism
  • DNA / chemistry
  • DNA / metabolism
  • G-Quadruplexes / drug effects*
  • Humans
  • Models, Molecular
  • Neoplasms / drug therapy
  • Organoplatinum Compounds / chemistry*
  • Organoplatinum Compounds / pharmacology*
  • Phenanthrenes / chemistry*
  • Phenanthrenes / pharmacology*
  • Telomere / drug effects*


  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Phenanthrenes
  • DNA