title: Identification of novel telomeric G-quadruplex-targeting chemical scaffolds through screening of three NCI libraries.
abstract: Thirteen compounds with diverse chemical structures have been identified as selective telomeric G-quadruplex-binding ligands through screening the NCI Diversity Set II, the NCI Natural Products Set II and the NCI Mechanistic Diversity Set libraries containing a total of 2307 members against a human telomeric G-quadruplex using a FRET-based DNA melting assay. These compounds show significant selectivity towards a telomeric G-quadruplex compared to duplex DNA, fall within a molecular weight range of 327-533, and are generally consistent with the Lipinski Rule of Five for drug-likeness. Thus they provide new chemical scaffolds for the development of novel classes of G-quadruplex-targeting agents.
authors.affiliation: The School of Pharmacy, University of London, London, United Kingdom.
authors.forename: Khondaker M
authors.initials: KM
authors.lastname: Rahman
authors.forename: Karolina
authors.initials: K
authors.lastname: Tizkova
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Reszka
authors.forename: Stephen
authors.initials: S
authors.lastname: Neidle
authors.forename: David E
authors.initials: DE
authors.lastname: Thurston
mesh_terms: D054856:G-Quadruplexes; D006801:Humans; D015394:Molecular Structure; D054547:National Cancer Institute (U.S.); D054852:Small Molecule Libraries / Q000737:chemistry*; D014481:United States
chemical_list: D054852:Small Molecule Libraries