Copper(ii) complexes with 4-acyl pyrazolone derivatives and diimine coligands: synthesis, structural characterization, DNA binding and antitumor activity

Abstract

Three mixed-ligand Cu(II) complexes [Cu(L)(bpy)] (1), [Cu(L)(phen)] (2) and [Cu(L)(dpq)]·CHCl₃ (3) have been synthesized and fully characterized, where H₂L = N-(1-phenyl-3-methyl-4-(4-fluorobenzoyl)-5-pyrazolone)-2-salicylidene hydrazide, bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline and dpq = dipyrido[3,2-d:2′,3′-f]quinoxaline. Single crystal X-ray diffraction analysis revealed that complexes 1–3 have mononuclear structure and the Cu(II) ions are located in a five-coordinated distorted square pyramidal geometry. The interaction of the compounds with herring sperm DNA has been studied by absorption titration, ethidium bromide displacement experiments and electrochemical studies. All the compounds could interact intercalatively with DNA, and complex 3 shows the highest DNA binding ability, followed by 2, 1 and H₂L. Complexes 1–3 exhibit excellent cytotoxicity against cervical cancer HeLa cells and human esophageal cancer Eca-109 cells. Complex 3 displays the best activity for both cancer cell lines, and the IC₅₀ values are 4.37 ± 0.08 μM and 3.68 ± 0.14 μM for HeLa and Eca-109 cells, respectively, which are about 13 times lower than that of the commercial antitumor drug cisplatin. Moreover, complex 3 dose-dependently induces Eca-109 cell apoptosis characterized by nuclear morphological changes and increased Annexin V⁺ cells, suggesting that complex 3 inhibited the proliferation of Eca-109 cells by induction of apoptosis. In conclusion, the mixed-ligand complex 3 might be a potential antitumor drug.