Mixed ligand complexes of Cu(II)/Zn(II) ions containing (m-)/(p-) carboxylato phenyl azo pentane 2,4-dione and 2,2′-bipyridine/1,10 phenanthroline: Synthesis, characterization, DNA binding, nuclease and topoisomerase I inhibitory activity

•Four type of Cu(II)/Zn(II) complexes are prepared and characterized.•The binding of complexes with CT DNA is monitored using UV–vis spectral titrations.•Complexes displace intercalator (ethidium bromide) bound to DNA.•The complexes 3 and 4 inhibit topoisomerase I activity.

Metal complexes of type [Cu(L1H)2(bpy)] (1), [Zn(L1H)2(bpy)] (2), [Cu(L2H)2(bpy)] (3) and [Cu(L2H)2(Phen)] (4) (L1H2 = 3-[N′-(1-acetyl-2-oxo-propylidene)-hydrazino]-benzoic acid, L2H2 = 4-[N′-(1-acetyl-2-oxo-propylidene)-hydrazino]-benzoic acid, bpy = 2,2′-bipyridine, Phen = 1,10 phenanthroline) are synthesized and characterized using spectroscopic techniques (FT-IR, 1H NMR, 13C NMR, electronic absorption and emission) and elemental analysis data. The assembly of the complexes involving intramolecular H-bonding is displayed using corresponding crystal structure. Binding of the complexes separately with Calf Thymus DNA is monitored using UV–vis spectral titrations. The displacement of ethidium bromide (EB) bound to DNA by the complexes, in phosphate buffer solution (pH ∼ 7.2) is monitored using fluorescence spectral titrations. Nuclease activity of the complexes follow the order 4 > 3 > 1 > 2. The gel electrophoretic mobility assay measurement in presence of minor groove binder 4′,6-diamidino-2-phenylindole (DAPI), suggests that complexes preferably bind with the minor groove of DNA. Topoisomerase I inhibitory activity of the complexes 3 and 4 inhibit topoisomerase I activity with IC50 values of 112 and 87 μM respectively.

Graphical abstractAzodiketone appended with m- and p-substituted phenyl carboxylates are complexed with Cu(II)/Zn(II) ions protected with bpy/Phen rings and characterized. Their nuclease and topoisomerase I inhibitory activity are measured using spectral titrations and gel electrophoretic mobility assay.Figure optionsDownload full-size imageDownload as PowerPoint slide