Novel platinum complexes as efficient G-quadruplex DNA binders and telomerase inhibitors

Three 4-(1H-imidazo[4,54]-1,10-phenanthrolin-2-yephenol derivatives-based platinum (II) complexes have been synthesized, and their G-quadruplex DNAs-binding interactions, telomerase inhibition, antiproliferative activity, and cell cycle arrest were studied. Three complexes show the preference for stabilizing h-telo, c-kit2, and c-myc G-quadruplexes in the presence of 10-fold excess of duplex DNA and the higher binding affinities to G-quadruplexes than to duplex. The complexes 1 and 3 present a high stabilization potential (Delta T-m) for h-telo G-quadruplex and thus give a significant inhibition of telomerase activity at 2 mu M concentration, whereas the complex 2 displays higher antiproliferative activity against HeLa and HepG2 cancer cells by MIT assay with IC50 values of about 10(-5) M. The complexes 2 and 3 arrest both cells in the G(0)/G(1) phase of cell cycle, whereas the complex 1 arrests the cell cycle in the S phase for HeLa cells and the G(0)/G(1) phase for HepG2 cells. (C) 2013 Elsevier B.V. All rights reserved.