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Structural analysis and biological functionalities of iron(III)– and manganese(III)–thiosemicarbazone complexes: in vitro anti-proliferative activity on human cancer cells, DNA binding and cleavage studies

  • Büşra Kaya
  • Zehra Kübra Yılmaz
  • Onur Şahin
  • Belma Aslim
  • Ümmügülsüm Tükenmez
  • Bahri ÜlküsevenEmail author
Original Paper
  • 263 Downloads

Abstract

One iron(III) and two manganese(III) complexes based on thiosemicarbazone were synthesized and characterized using analytical and spectroscopic data. The crystallographic analysis showed the square pyramid structures of the complexes. Electronic spectra analysis was performed to determine the nature of the interaction between the complexes and calf thymus DNA (CT-DNA). DNA cleavage activities of the complexes were examined by gel electrophoresis (pBR322 DNA). The cytotoxicity of the complexes was determined against human cervical carcinoma (HeLa) and human colorectal adenocarcinoma (HT-29) cell lines by MTT assay. The results indicated that complex Fe1 is bound to CT-DNA via the intercalation mode, while complexes Mn1 and Mn2 are bound to CT-DNA via groove binding and/or electrostatic interactions rather than the intercalation mode. In addition, they showed good binding activity, which followed the order of Fe1 > Mn2 > Mn1. Complexes were found to promote the cleavage of DNA from supercoiled form (SC, Form I) to nicked circular form (NC, Form II) without concurrent formation of Form III, revealing the single-strand DNA cleavage. No significant cleavage was found in the presence of Mn1 and Mn2; however, it was observed at 2000 and 3000 µM concentrations of Fe1. The ability of Fe1 to cleave DNA was greater than that of other complexes and these results are in conformity with their DNA-binding affinities. Cytotoxicity determination tests revealed that the complex Fe1 on HeLa and HT-29 cells exhibited a higher anti-proliferative effect than Mn1 and Mn2 (Fe1 > Mn2 > Mn1). These studies suggested that the complex Fe1 could be a good candidate as a chemotherapeutic drug targeting DNA.

Graphical abstract

Keywords

Thiosemicarbazone Iron Manganese DNA binding DNA cleavage Anti-proliferation 

Notes

Acknowledgements

This work was supported by the Scientific Research Projects Coordination Unit of Istanbul University-Cerrahpasa. The authors acknowledge Scientific and Technological Research Application and Research Center, Sinop University, Turkey, for the use of the Bruker D8-QUEST diffractometer.

Supplementary material

775_2019_1653_MOESM1_ESM.pdf (181 kb)
Crystallographic data for the structural analysis have been deposited with the Cambridge Crystallographic Data Centre, CCDC No. 1877123 for Fe1 and 1877124 for Mn1. Copies of this information may be obtained free of charge from the Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: +44-1223-336033; e-mail: deposit@ccdc.cam.ac.uk or www: http://www.ccdc.cam.ac.uk) (PDF 180 kb)

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Copyright information

© Society for Biological Inorganic Chemistry (SBIC) 2019

Authors and Affiliations

  • Büşra Kaya
    • 1
  • Zehra Kübra Yılmaz
    • 2
  • Onur Şahin
    • 3
  • Belma Aslim
    • 2
  • Ümmügülsüm Tükenmez
    • 4
  • Bahri Ülküseven
    • 1
    Email author
  1. 1.Department of Chemistry, Engineering FacultyIstanbul University-CerrahpasaIstanbulTurkey
  2. 2.Faculty of Science, Department of BiologyGazi UniversityAnkaraTurkey
  3. 3.Scientific and Technological Research Application and Research CenterSinop UniversitySinopTurkey
  4. 4.Vocational High School of Health ServicesMardin Artuklu UniversityMardinTurkey

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