A series of novel 2,4,6-triarylpyridines have been synthesized and their interactions with intramolecular G-quadruplexes have been measured by Forster 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.
Smith, N., Labrunie, G., Corry, B., Tran, P. L. T., Norret, M., Djavaheri-Mergny, M., ... Mergny, J. L. (2011). Unraveling the relationship between structure and stabilization of triarylpyridines as G-quadruplex binding ligands. Organic & Biomolecular Chemistry, 9, 6154-6162. https://doi.org/10.1039/c1ob05560g