DNA binding, cleavage and anticancer activity of a Zn(II)-Cu(II) hetero-dinuclear carbohydrazone complex containing the secondary ligand 1,10-phenanthroline

Abstract

A hetero di-nuclear complex [Zn(o-phen)LCu(OAc)] (1) (H3L = o-HOC6H4CH = NNH)2C = O, o-phen = 1,10-phenanthroline) exhibited intercalative DNA binding (Kb = 1.03 × 105 M−1) as revealed from UV–Vis spectral analysis as well as viscosity study and further supported by molecular docking study of 1 with DNA. The apparentbinding constant (Kapp = 21.78 × 105 M−1) obtained from ethidium bromide (EB) displacement assay using fluorescence spectral study further confirmed the efficient binding ability of the complex to DNA. The complex displayed both oxidative as well as hydrolytic DNA cleavage activity. Quantitative hydrolytic cleavage results suggested significant nuclease activity against PUC19 plasmid DNA. Oxidative DNA cleavage experiments done with ROS (reactive oxygen species) scavengers showed the involvement of •OH in the cleavage mechanism. Anticancer activity of 1 was tested by evaluating the cytotoxicity of the complex towards cervical cancer HeLa, cisplatin resistant breast cancer MDA-MB-231 and epidermoid carcinoma A431 cells. IC50 values (11.08 ± 1.1 µM for HeLa, 2.75 ± 0.16 µM for MDA-MB-231 and 1.38 ± 0.07 µM for A431 cells) revealed significant cell death in all three cell lines. Nuclear staining using AO/PI and Hoechst 33,342 suggested cell death occurred due to apoptosis in these cancer cells. 1 induced high level of ROS in HeLa cells. It also caused G2/M phase arrest in HeLa cells as revealed from cell cycle analysis.