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 of MOIP show growth inhibitions on 4 tumour cell lines.
• The complexes block cell cycle at sub-G1 phase and induce apoptosis in HeLa cells.
• The complexes induce and stabilize the formation of human telomeric G-quadruplex DNA.
• The 2-methoxy ligand with lower steric hindrance has better DNA binding affinity.

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.

Three platinum(II) complexes 1–3 bearing with 2-(methoxy-phenyl)imidazo[4,5-f]-[1,10] phenanthroline ligands showed higher cytotoxicities against SPC-A-2, MGC80-3, BEL-7404 and HeLa human tumour cell lines with IC50 values in the range of 4.7–23.3 μM than the HL-7702 normal liver cell line. They significantly induced cell apoptosis and blocked the cell cycle at sub-G1 phase in HeLa cells, in which the 2-methoxy substituted ligand showed the better cell apoptosis induction. Complexes 1–3 also suggested potent inhibitions on telomerase activity due to their higher binding affinities with human telomeric G-quadruplex DNA than with double helix DNA.Figure optionsDownload as PowerPoint slide