Stabilization of G-quadruplex DNA and inhibition of telomerase activity studies of ruthenium(II) complexes

摘要

Two ruthenium(II) complexes [Ru(IP)_2(PIP)](ClO_4)_2·2H_2O (1) and [Ru(PIP)_2(IP)](ClO_4)_2·2H_2O (2) (IP = imidazole [4, 5-f] [1,10] phenanthroline, PIP = 2-phenylimidazo-[4, 5-f][1,10] phenanthroline) have been synthesized and characterized. The quadruplex binding of the compounds was evaluated by emission spectrum, CD spectroscopy, Visual detection assay and FRET (fluorescence resonance energy transfer)-melting assay. The results show that both complexes can induce the stabilization of quadruplex DNA, while complex 1 is a better G-quadruplex binder than complex 2. Furthermore, polymerase chain reaction-stop assay, electrophoretic mobility shift assay, telomerase repeat amplification protocol and MTT (3-[4,5-Dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide) assay demonstrate that complex 1 not only can stabilize dimer forms of the G-quadruplex at low concentrations but also exhibit better inhibitory activity for telomerase and cancer cells.