Anticancer activity of novel ruthenium complex with 1,10-phenanthrolineselenazole as potent telomeric G-quadruplex inhibitor

A novel Ru(II)-selenium complex [Ru(phen)(2)L](ClO4)(2) (Phen = 1,10-phenanthroline, L = 1,10-phenanthrolineselenazole) has been synthesized and structurally characterized by elemental analysis, ESI-MS and H-1 NMR spectra, and the interaction between human telomeric G-quadruplex DNA (HTG21) and the new compound has been studied by emission spectra, visual detection assay, circular dichroism (CD) spectroscopy and fluorescence resonance energy transfer (FRET) melting assay. The results show that the complex has interaction with human telomeric G-quadruplex DNA which is visually detected, meanwhile it induces the guanine-rich single-strand oligomer d[G(3)(T(2)AG(3))(3)] to form antiparallel G-quadruplex and has a moderate ability to stabilize G-quadruplex structures (Delta T-m = 11.2 degrees C). Furthermore, polymerase chain reaction-stop assay, telomerase repeat amplification protocol, and MU assay demonstrate that the Ru-complex can exhibit well inhibitory activity for telomerase and cancer cells. The results suggest that Ru-complex may be a potential telomerase inhibitor for cancer chemotherapy. (C) 2012 Elsevier B.V. All rights reserved.