Synthesis, cytotoxicity and DNA binding of novel Ni(II), Co(II) and Zn(II) complexes bearing pyrimidinyl hydrazone ligand

Abstract

To develop efficient new antitumor agents, Ni(II), Co(II) and Zn(II) complexes 1–3 derived from 2-((2-pyrimidin-2-yl)hydrazono)methyl)quinoline (HL) were prepared and structurally characterized using IR, elemental analysis, UV-Vis, fluorescence spectrometry and single crystal X-ray diffraction analysis. The in vitro cytotoxicity of complexes 1–3 against MCF-7, BGC-823, A549, BEL-7402 tumor cell lines and human normal cell line HL-7702 was evaluated using MTT assay. Complexes 1-3 display higher cytotoxic activity than cisplatin as well as HL against BGC-823 tumor cell line, with IC50 values ranging from 5.57 µM to 11.20 µM, and less toxicity toward the normal cell line HL-7702. In particular, complex 3 exhibits the most prominent antiproliferative activity. Complex 3 was found to induce apoptosis of BGC-823 cells greatly in a dose-dependent manner, which was suggested by Annexin V-FITC/PI and AO/EB dual-staining assays. The DNA binding studies, which were performed using UV-Vis, fluorescence and CD spectral analyzes, revealed that complex 3 interacts with CT-DNA mainly via a partial intercalative binding mode. The molecular docking of the interaction of complex 3 with DNA is in accordance with the experimental data.