Looking for efficient G-quadruplex ligands: evidence for selective stabilizing properties and telomere damage by drug-like molecules

ChemMedChem. 2015 Apr;10(4):640-9. doi: 10.1002/cmdc.201402552. Epub 2015 Feb 18.

Abstract

There is currently significant interest in the development of G-quadruplex-interactive compounds, given the relationship between the ability to stabilize these non-canonical DNA structures and anticancer activity. In this study, a set of biophysical assays was applied to evaluate the binding of six drug-like ligands to DNA G-quadruplexes with different folding topologies. Interestingly, two of the investigated ligands showed selective G-quadruplex-stabilizing properties and biological activity. These compounds may represent useful leads for the development of more potent and selective ligands.

Keywords: DNA recognition; DNA structures; G-quadruplexes; anticancer agents; biological activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Base Sequence
  • Cell Line
  • DNA / chemistry
  • Drug Design*
  • G-Quadruplexes / drug effects*
  • Humans
  • Ligands
  • Molecular Docking Simulation
  • Nucleic Acid Denaturation / drug effects
  • Telomere / chemistry
  • Telomere / drug effects*

Substances

  • Antineoplastic Agents
  • Ligands
  • DNA