Three platinum (II) complexes of 2-(methoxy-phenyl)-imidazo-[4,5-f]-[1,10] phenanthroline: cell apoptosis induction by sub-G1 phase cell cycle arrest and G-quadruplex binding properties

Three platinum(II) complexes, including 2-(2-methoxy-phenyl) imidazo [4,5-f]-[1,10] phenanthroline, 2-(3-methoxy-phenyl) imidazo [4,5-f]-[1,10] phenanthroline and 2-(4-methoxy-phenyl) imidazo 14,541-[1,10] phenanthroline, were synthesised and structurally characterised. In complexes 1-3, the platinum centre adopts a four-coordinate square planar geometry. In the MU assay, these complexes exhibited considerable cytotoxicities against the SPC-A-2, MGC80-3, BEL-7404 and HeLa human tumour cell lines, with IC50 values in the range of 4.7 +/- 0.8 to 23.3 +/- 0.4 mu M, and lower cytotoxicities towards the HL-7702 human normal liver cell line. By flow cytometry analyses, the HeLa cells treated with complexes 1-3 for 72 h exhibited DNA damage at the sub-G1 phase with a dose-dependent effect resulting in the blockage of cell cycle at sub-G1 phase, which might contribute to the cell apoptosis observed in HeLa cells. From the results of the CD, UV-vis and FID spectral analyses, complexes 1-3 showed good binding affinity with human telomeric G-quadruplex DNA. It suggested the potential inhibition on the telomerase activity, which should be a key antitumour mechanism for complexes 1-3. Furthermore, complex 1 with 2-substituted MOIP ligand, which may have lower steric hindrance for DNA intercalation, showed higher G-quadruplex DNA binding affinity than complexes 2 and 3. This was supported by the results from cell growth inhibition and cell apoptosis induction. (C) 2014 Elsevier B.V. All rights reserved.