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Synthesis of Ni(II) complexes bearing indole-based thiosemicarbazone ligands for interaction with biomolecules and some biological applications

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Abstract

A series of new Ni(II) complexes containing indole-based thiosemicarbazone ligands was synthesized and characterized by elemental analyses, and UV–visible, FT-IR, 1H & 13C NMR and mass spectroscopic techniques. The Ni(II) complexes (1–4) bear the general formula [Ni{C10H9N2NHCSNH(R)}2] where R = hydrogen (1), 4-methyl (2), 4-phenyl (3) and 4-cyclohexyl (4). Molecular structure of ligands (L3 and L4) and complexes (2, 3 and 4) was confirmed by single crystal X-ray crystallography. Four coordinated Ni(II) complexes showed square planar geometry. The interaction of the Ni(II) complexes with calf thymus DNA (CT-DNA) has been evaluated by absorption spectroscopic and ethidium bromide (EB) competitive binding studies, which revealed the intercalative interaction of the complexes with CT-DNA. Gel electrophoresis experiments showed the cleavage of DNA by the complexes without any external agent. Further, the interaction of the complexes with bovine serum albumin (BSA) was investigated using UV–visible, fluorescence and synchronous fluorescence spectroscopic methods, which showed that the complexes could bind strongly with BSA. Molecular docking was employed to understand the binding of the Ni(II) complexes with the molecular target B-DNA, human DNA topoisomerase I and BSA. All the Ni(II) complexes possess high antioxidant activity against 2-2-diphenyl-1-picrylhydrazyl (DPPH) radical and antihaemolytic activity. In addition, in vitro cytotoxicity of the Ni(II) complexes against lung cancer (A549), human breast cancer (MCF7) and mouse embryonic fibroblasts (L929) cell lines was investigated. Complex 4 has high cytotoxicity. The mode of cell death effected by complex 4 has been explored using Hoechst 33258 staining.

Graphical abstract

Nickel(II) complexes of thiosemicarbazone ligands were synthesized and their DNA/protein binding, DNA cleavage and cytotoxicity abilities were studied.

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Acknowledgements

JH thanks the University Grants Commission for the fellowship (F1-17.1/2012-13/RGNF-2012-13-ST-AND-18716).

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Authors and Affiliations

  1. Department of Chemistry, National Institute of Technology, Tiruchirappalli, 620015, India

    Jebiti Haribabu, Kumaramangalam Jeyalakshmi & Ramasamy Karvembu

  2. Organic Chemistry Division, CSIR-Central Leather Research Institute, Chennai, 600020, India

    Yuvaraj Arun & Paramasivan Thirumalai Perumal

  3. Department of Chemistry, Texas A&M University, College Station, TX, 77842, USA

    Nattamai S. P. Bhuvanesh

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  1. Jebiti Haribabu
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  2. Kumaramangalam Jeyalakshmi
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Correspondence to Ramasamy Karvembu.

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775_2016_1424_MOESM1_ESM.pdf

Crystallographic data for the structures reported in this paper have been deposited with the Cambridge Crystallographic Data Centre (CCDC) as supplementary publication numbers (CCDC 1451697, CCDC 1451698, CCDC 1451699, CCDC 1451700 and CCDC 1451701 for L3, L4, 2, 3 and 4, respectively). Copies of the data can be obtained free of charge from the CCDC (http://www.ccdc.cam.ac.uk) (PDF 2668 kb)

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Haribabu, J., Jeyalakshmi, K., Arun, Y. et al. Synthesis of Ni(II) complexes bearing indole-based thiosemicarbazone ligands for interaction with biomolecules and some biological applications. J Biol Inorg Chem 22, 461–480 (2017). https://doi.org/10.1007/s00775-016-1424-1

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