Cadmium(II) complexes of a hydrazone ligand: Synthesis, characterization, DNA binding, cyto- and genotoxicity studies

Abstract

A new cadmium(II) complex, {[Cd(L)(NO2)(CH3CH2OH)]·H2O}n (1), based on HL Schiff base ligand (HL = 2-pyridinecarbaldehyde isonicotinoyl hydrazone) was synthesized and characterized by single crystal X-ray diffraction method. DNA binding interactions of the free HL ligand, complex 1 and another cadmium complex with the same Schiff base ligand, [Cd(L)(CH3COO)(OH2)]n (2), were investigated using UV–Vis absorption, viscosity and fluorescence studies. These compounds could bind with the calf thymus-DNA via intercalation. The binding strength of these compounds to DNA was in the order of 2 > 1 > HL with respect to their calculated Kb values (150.0, 143.0 and 87.5 kM−1, respectively). The calculated thermodynamic parameters showed that the binding process of all these compounds to DNA is spontaneous (ΔG° <0) and endothermic (ΔH° >0) associated with increasing entropy (ΔS° >0). Investigation of the cytotoxic activities of the two complexes against the human lung cancer cell line (A549) using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay showed that their activity is almost in the region of cisplatin but much more than that of free HL ligand (IC50 = 138.27 ± 1.20, 46.31 ± 0.40, 32.01 ± 0.33 and 37.71 ± 0.20 μM for HL, 1, 2 and cisplatin, respectively). The genotoxicity studies of the complexes including DNA fragmentation and DAPI [4′,6-diamidino-2-phenylindole] staining assays at IC50 (half maximal inhibitory) concentrations confirmed the induction of apoptosis and nuclear dysfunction by the complexes. Cell apoptosis induced by the complexes was detected through Annexin V/PI (propidium iodide) dual staining with flow cytometric analysis and the results indicated that the complex 2 has higher apoptotic activity than 1.