Triazolyl Dibenzo[]phenazines Stabilize Telomeric G-quadruplex and Inhibit Telomerase.

We herein report the synthesis and biophysical evaluation of triazolyl dibenzo[]phenazine derivatives as a novel class of G-quadruplex ligands. The aromatic core facilitates π-π interaction and the flexible, protonatable side chains interact with the phosphate backbone of DNA electrostatic interactions. Förster resonance energy transfer (FRET) melting assay and isothermal titration calorimetry (ITC) studies suggest that these ligands show binding preference for the G-quadruplex over G-quadruplexes found in the promoter region of various oncogenes and duplex DNA. The telomeric repeat amplification protocol (Q-TRAP) assay reveals that these ligands reduce telomerase activity in cancer cells.