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

Three 4-(1H-imidazo[4,5-f]-1,10-phenanthrolin-2-yl)phenol 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 (ΔTm) for h-telo G-quadruplex and thus give a significant inhibition of telomerase activity at 2 μM concentration, whereas the complex 2 displays higher antiproliferative activity against HeLa and HepG2 cancer cells by MTT assay with IC50 values of about 10−5 M. The complexes 2 and 3 arrest both cells in the G0/G1 phase of cell cycle, whereas the complex 1 arrests the cell cycle in the S phase for HeLa cells and the G0/G1 phase for HepG2 cells.

► Complexes can bind selectively to G-quadruplex over duplex.
► Complexes can stabilize the structures of G-quadruplex DNAs.
► Complexes inhibit significantly the telomerase activity at 2 μM concentration.