A series of DNA targeted Cu (II) complexes containing 1,8-naphthalimide ligands: Synthesis, characterization and in vitro anticancer activity.

Copper(II) complexes are very promising candidates for platinum-based anticancer agents. Herein, three Cu (II) complexes (1 – 3) containing 1,8-naphthalimide ligands were synthesized and characterized by FT-IR, elemental analysis, ESI-MS and single crystal X-ray diffraction (complex 3). In addition, a control compound (complex 4) without 1,8-naphthalimide ligand was synthesized and characterized. The in vitro anticancer activity of the synthesized complexes against five cancer cell lines and one normal cell line was evaluated by MTS assay. The results displayed the antitumor activity of complexes 1 – 3 was controlled by the aliphatic chain length of ligands, their cytotoxicity was in the order 3 > 2 > 1 , giving the IC 50 values ranging from 2.874 ± 0.155 μM to 31.47 ± 0.29 μM against five cancer cell lines. Complex 4 showed less activity in comparison with complex 1 – 3. Notably, complexes 1 – 3 displayed much higher selectivity (SI = 2.65 to 10.16) compared to complex 4 (SI = 1.0), indicated that the introduction of 1,8-naphthalimide group not only increased the activity of this series of compounds but also enhanced their specific selectivity to cancer cells. Compound 3 induced apoptosis in cancer cells and blocked the S-phase and G2/M of cancer cells. The interaction with DNA of complexes 3 and 4 was studied by UV/Vis spectroscopic titrations, competitive DNA-binding experiment, viscometry and CD spectra. The results showed that complex 3 interacted with DNA in an intercalating mode, but the interaction mode of compound 4 with DNA was electrostatic interaction. A series of DNA targeted Cu (II) complexes containing 1,8-naphthalimide ligands displayed a potent and selective anticancer activity. [Display omitted] • A series of DNA targeted Cu (II) complexes containing 1,8-naphthalimide ligands displayed a potent anticancer activity. • The introduction of 1,8-naphthalimide improved both the anticancer activity and selectivity of the series of copper (II) complexes. • The aliphatic chain length of ligands regulated the anticancer activity of this series of compounds. [ABSTRACT FROM AUTHOR]