Stabilization of G-quadruplex DNA and antitumor activity by different structures of nickel (II) complexes

Abstract

Abstract In the present investigation, four nickel (II) complexes [Ni(bpy)3]2 + NB, [Ni(phen)3]2 + NP, [Ni(bpy)2(p-ipip)]2 + NBH and [Ni(phen)2(p-ipip)]2 + NPH were synthesized and characterized by electrospray ionization-mass spectrometry, where phen is 1,10-phenanthroline, bpy is 2,2′-bipyridine and p-ipip is 2-(4-indole)-imidazo[4,5f][1,10] phenanthroline. The interactions of human telomeric G-quadruplex DNA with these designed complexes were evaluated by CD spectroscopy, fluorescence resonance energy transfer (FRET) melting assay and FRET competitive binding experiment. The experimental evidence indicated that all complexes could strongly bind to and effectively stabilize the telomeric G-quadruplex DNA. Complex NPH was a better G-quadruplex binder than other complexes. Furthermore, polymerase chain reaction (PCR)-stop assay, gel mobility shift assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay demonstrated that complex NPH not only can stabilize dimers forms of the G-quadruplex at low concentrations but also high inhibitory selectivity against cancer cells. The results suggest that complex NPH may be a potential telomerase inhibitor for cancer chemotherapy.