Stabilization of G-quadruplex DNA and inhibition of telomerase activity studies of ruthenium(II) complexes

J Inorg Biochem. 2014 Jan:130:122-9. doi: 10.1016/j.jinorgbio.2013.10.006. Epub 2013 Oct 12.

Abstract

Two ruthenium(II) complexes [Ru(IP)2(PIP)](ClO4)2·2H2O (1) and [Ru(PIP)2(IP)](ClO4)2·2H2O (2) (IP=imidazole [4, 5-f] [1,10] phenanthroline, PIP=2-phenylimidazo-[4, 5-f][1,10] phenanthroline) have been synthesized and characterized. The quadruplex binding of the compounds was evaluated by emission spectrum, CD spectroscopy, Visual detection assay and FRET (fluorescence resonance energy transfer)-melting assay. The results show that both complexes can induce the stabilization of quadruplex DNA, while complex 1 is a better G-quadruplex binder than complex 2. Furthermore, polymerase chain reaction-stop assay, electrophoretic mobility shift assay, telomerase repeat amplification protocol and MTT (3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay demonstrate that complex 1 not only can stabilize dimer forms of the G-quadruplex at low concentrations but also exhibit better inhibitory activity for telomerase and cancer cells.

Keywords: Anticancer activity; G-quadruplex DNA; Ruthenium(II) complexes; Telomerase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Circular Dichroism
  • Dose-Response Relationship, Drug
  • Electrophoretic Mobility Shift Assay
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Fluorescence Resonance Energy Transfer
  • G-Quadruplexes*
  • HeLa Cells / drug effects
  • Humans
  • Molecular Structure
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry*
  • Organometallic Compounds / pharmacology*
  • Ruthenium / chemistry*
  • Telomerase / antagonists & inhibitors*

Substances

  • Enzyme Inhibitors
  • Organometallic Compounds
  • Ruthenium
  • Telomerase