Unraveling the relationship between structure and stabilization of triarylpyridines as G-quadruplex binding ligands

Org Biomol Chem. 2011 Sep 7;9(17):6154-62. doi: 10.1039/c1ob05560g. Epub 2011 Jul 13.

Abstract

A series of novel 2,4,6-triarylpyridines have been synthesized and their interactions with intramolecular G-quadruplexes have been measured by Förster Resonance Energy Transfer (FRET) melting and Fluorescent Intercalator Displacement (FID) assays. A few of these compounds exhibit stabilization of G4-DNA that is comparable to other benchmark G4-DNA ligands with fair to excellent G4-DNA vs. duplex selectivity and significant cytotoxicity towards HeLa cells. The nature of the 4-aryl substituents along with side chain length governs the G4-DNA stabilization ability of the compounds. In addition, we demonstrate that there is a strong correlation between the ability of the compounds to stabilize the same G4-DNA sequence in K(+) and Na(+) conditions and a strong correlation between the ability of the compounds to stabilize different G4-DNA sequences in K(+) or Na(+) buffer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Binding Sites
  • Cell Survival / drug effects
  • DNA / chemistry
  • DNA / metabolism*
  • Fluorescence Resonance Energy Transfer
  • G-Quadruplexes*
  • HeLa Cells
  • Humans
  • Ligands
  • Neoplasms / drug therapy
  • Pyridines / chemistry*
  • Pyridines / pharmacology*

Substances

  • Antineoplastic Agents
  • Ligands
  • Pyridines
  • DNA