DNA binding, DNA cleavage and cytotoxicity studies of a new water soluble copper(II) complex: The effect of ligand shape on the mode of binding

The interaction of native calf thymus DNA (CT-DNA) with [Cu(ph2phen)(phen-dione)Cl]Cl was studied at physiological pH by spectrophotometric, spectrofluorometric, circular dichroism, and viscometric techniques.Considerable hypochromicity and red shift are observed in the UV absorption band of the Cu complex. Binding constants (Kb) of DNA with the complex were calculated at different temperatures. Thermodynamic parameters, enthalpy and entropy changes were calculated according to Van’t Hoff equation, which indicated that reaction is predominantly enthalpically driven. All these results indicate that Cu(II) complex interacts with CT-DNA via intercalative mode. Also, this new complex induced cleavage in pUC18 plasmid DNA as indicated in gel electrophoresis and showed excellent antitumor activity against K562 (human chronic myeloid leukemia) and human T lymphocyte carcinoma-Jurkat cell lines.

Binding interaction of water soluble copper(II) complex [Cu(ph2phen)(phen-dione)Cl]Cl, with calf thymus DNA (CT-DNA) has been investigated by instrumental method, also, DNA cleavage and cytotoxicity effect have been studied. The binding mode was determined to be intercalation.Figure optionsDownload as PowerPoint slideHighlights
► This study is a good suggestion to design improved drugs that target the cellular DNA.
► It was studied the relationship between DNA-binding affinities and ligand shape.
► The calculation of thermodynamic parameters indicated that reaction is enthalpically driven.
► This new complex showed, cleavage in plasmid DNA and excellent antitumor activity.