Two water-soluble copper(II) complexes: Synthesis, characterization, DNA cleavage, protein binding activities and in vitro anticancer activity studies
摘要:
Two water-soluble ternary copper(II) complexes of [Cu(L)CI](ClO4) (1) and [Cu(L)Br-2] (2) (L = (2-((quinolin-8-ylimino)methyl)pyridine)) were prepared and characterized by various physico-chemical techniques. Both 1 and 2 were structurally characterized by X-ray crystallography. The crystal structures show the presence of a distorted square-pyramidal CuN3Cl2 (1) or CuN3Br2 (2) geometry in which Schiff-base L acts as a neutral tridentate ligand. Both complexes present intermolecular pi-pi stacking interactions between quinoline and pyridine rings. The interaction of two complexes with CT-DNA (calf thymus-DNA) and BSA (bovine serum albumin) was studied by means of various spectroscopy methods, which revealed that 1 and 2 could interact with CT-DNA through intercalation mode, and could quench the intrinsic fluorescence of BSA in a static quenching process. Furthermore, the competition experiment using Hoechst 33258 indicated that two complexes may bind to CT-DNA by a minor groove. DNA cleavage experiments indicate that the complexes exhibit efficient DNA cleavage activities without any external agents, and hydroxyl radical (HO) and singlet oxygen (O-1(2)) may serve as the major cleavage active species. Notably, the in vitro cytotoxicity of the complexes on three human tumor cells lines (HeLa, MCF-7, and A549) demonstrates that two compounds have broad-spectrum antitumor activity with quite low IC50 ranges of 0.43-1.85 mu M. Based on the cell cycle experiments, 1 and 2 could delay or inhibit cell cycle progression through the S phase. (C) 2014 Elsevier Inc. All rights reserved.