title: Unraveling the relationship between structure and stabilization of triarylpyridines as G-quadruplex binding ligands.
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.
authors.affiliation: Centre for Strategic Nano-Fabrication, School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, Crawley, WA-6009, Australia.
authors.forename: N M
authors.initials: NM
authors.lastname: Smith
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Labrunie
authors.forename: Ben
authors.initials: B
authors.lastname: Corry
authors.forename: Phong Lan Thao
authors.initials: PL
authors.lastname: Tran
authors.forename: Marck
authors.initials: M
authors.lastname: Norret
authors.forename: Mojgan
authors.initials: M
authors.lastname: Djavaheri-Mergny
authors.forename: Colin L
authors.initials: CL
authors.lastname: Raston
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mergny
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000188:drug therapy; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D011725:Pyridines; D004247:DNA