Platinum(II) complexes with dipyridophenazine ligands as human telomerase inhibitors and luminescent probes for G-quadruplex DNA

Abstract

A series of platinum(ll) complexes containing dipyridophenazine (dppz) and C-deprotonated 2-phenylpyridine (N^CH) ligands were prepared and assayed for G-quadruplex DNA binding activities. [Pt"(dppz-COOH)(N^C)]CF 3S03 (1; dppz-COOH = 11-carboxydipyrido[3,2-a:2,3-c] phenazine) binds G-quadruplex DNA through an external end-stacking mode with a binding affinity of ̃107 dm3 mol-1. G-quadruplex DNA binding is accompanied by up to a 293-fold increase in the intensity of photoluminescence at λmax = 512 nm. Using a biotinylated-primer extension telomerase assay, 1 was shown to be an effective inhibitor of human telomerase in vitro, with a telIC50 value of 760 nM. © 2009 American Chemical Society.