Screening of Scaffolds for the Design of G-Quadruplex Ligands

In the last decade, progress has been made in G-quadruplex (G4) ligands development, but for most compounds, ligand binding mode is speculative or based on low resolution methods, with its discovery structure-based approaches. Herein, we report synthesis of small (MW < 400 Da) heterocycle containing different aromatic scaffolds, such as phenyl, quinoline, naphthalene, phenanthroline and acridine moieties, order to explore their stabilization effect towards DNA G4s, those found c-MYC, KRAS21 VEGF promoters, 21G human telomeric motif pre-MIR150. The fluorescence resonance energy transfer (FRET) melting assay indicates that moiety active scaffold, followed by phenanthroline. scaffolds are promising terms drug-like properties and, general, IC50 values respective compounds lower a cancer cell line, when compared normal line. derivative C5NH2 favorable cytotoxic profile selectivity.