Synthesis, X-ray crystal structure, DNA/protein binding, DNA cleavage and cytotoxicity studies of N(4) substituted thiosemicarbazone based copper(II)/nickel(II) complexes

•Novel Cu(II) and Ni(II) complexes have been prepared and confirmed by XRD studies.•Cu(II) and Ni(II) complexes interacted with DNA/BSA and cleaved DNA without any external agents.•Cytotoxicity study of the complexes found significant activity against A549 and L929.

N-ethyl-2-(phenyl(pyridin-2-yl)methylene)hydrazinecarbothioamide (HBpyeTsc) was obtained from 4-ethyl-3-thiosemicarbazide and 2-benzoylpyridine. The complexes (CuBpyeTscCl) and Ni[BpyeTsc]2Cl2 were synthesized from HBpyeTsc and [CuCl2·2H2O]/[NiCl2·6H2O]. The synthesized ligand and complexes were characterized by analytical and various spectroscopic techniques. The molecular structure of the ligand and complexes was determined by single crystal X-ray diffraction method. The single crystal X-ray diffraction revealed that CuBpyeTscCl and Ni[BpyeTsc]2Cl2 exhibited square planar and distorted octahedral geometry respectively. All of the synthesized compounds HBpyeTsc, CuBpyeTscCl and Ni[BpyeTsc]2Cl2 were studied for their interaction with calf thymus DNA (CT DNA) and bovine serum albumin (BSA). A DNA cleavage study showed that the complexes cleaved DNA without any external agent. The alterations in the secondary structure of the protein by the ligand and complexes were confirmed by synchronous fluorescence spectroscopic studies. Spectral evidences also showed good binding property of the complexes with the protein. An in vitro cytotoxicity study of the complexes found significant activity against lung cancer cell lines (A549) and less toxicity toward the normal cell lines (L929). The best results for the copper(II) and nickel(II) complexes are the IC50 values of 56.07 and 80.10 μM respectively.

Graphical abstractCopper(II) and nickel(II) complexes containing thiosemicarbozone ligand have been synthesized and evaluated for its biological applications like DNA/protein binding, DNA cleavage and cytotoxicity studies.Figure optionsDownload full-size imageDownload as PowerPoint slide