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 4,5-f]-1,10] phenanthroline, were synthesised and structurally characterised. In complexes 1–3, the platinum centre adopts a four-coordinate square planar geometry. In the MTT 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 μM, 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.