Ternary Dinuclear Copper(II) Complexes of a Reduced Schiff Base Ligand with Diimine Coligands: DNA Binding, Cytotoxic Cell Apoptosis, and Apoptotic Mechanism

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Abstract

A serial of mixed-ligand Cu(II) complexes of the type [Cu(phens)(H2PDILeu)]H2O (1-4) containing phens as 2,2′-bipyridyl (bpy, 1), 1,10-phenanthroline (phen, 2), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq, 3), and dipyrido[3,2-a:2′,3′-c]phenazine (dppz, 4) have been isolated and characterized. The interaction of the complexes with calf-thymus DNA has been explored by physical methods to propose modes of DNA binding of the complexes, which indicate that 4 interacts with DNA more strongly than all of the other complexes through intercalation interaction. Furthermore, cell apoptosis was detected by AnnexinV/PI flow cytometry and TUNEL assay and by Western blotting to detect the protein expression of p53, Bax, and Bcl-2. All the three copper complexes can effectively induce apoptosis of the three human tumor cells, which was accompanied with upregulation of the expression of p53 and Bax, while Bcl-2 decreased.

A serial of mixed ligand Cu(II) complexes have been isolated and characterized. The interaction of the complexes with calf thymus DNA has been explored by using physical methods to propose modes of DNA binding of the complexes, which indicate that 4 interacts with DNA more strongly than all of the other complexes through intercalation interaction.

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