Platinum(II) Complexes with Dipyridophenazine Ligands as Human Telomerase Inhibitors and Luminescent Probes for G-Quadruplex DNA

A series of platinum(II) complexes containing dipyridophenazine (dppz) and C-deprotonated 2-phenylpyridine ((NCH)-C-boolean AND) ligands were prepared and assayed for G-quadruplex DNA binding activities. [Pt-II(dppz-COOH)((NC)-C-boolean AND)]CF3SO3 (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 similar to 10(7) dm(3) mol(-1). G-quadruplex DNA binding is accompanied by up to a 293-fold increase in the intensity of photoluminescence at lambda(max) = 512 nm. Using a biotinylated-primer extension telomerase assay, 1 was shown to be an effective inhibitor of human telomerase in vitro, with a (IC50)-I-tel value of 760 nM.