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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

Authors
  • Kaya, Büşra1
  • Yılmaz, Zehra Kübra2
  • Şahin, Onur3
  • Aslim, Belma2
  • Tükenmez, Ümmügülsüm4
  • Ülküseven, Bahri1
  • 1 Istanbul University-Cerrahpasa, Department of Chemistry, Engineering Faculty, Avcilar, Istanbul, 34320, Turkey , Istanbul (Turkey)
  • 2 Gazi University, Faculty of Science, Department of Biology, Ankara, Turkey , Ankara (Turkey)
  • 3 Sinop University, Scientific and Technological Research Application and Research Center, Sinop, 57000, Turkey , Sinop (Turkey)
  • 4 Mardin Artuklu University, Vocational High School of Health Services, Mardin, Turkey , Mardin (Turkey)
Type
Published Article
Journal
JBIC Journal of Biological Inorganic Chemistry
Publisher
Springer-Verlag
Publication Date
Mar 20, 2019
Volume
24
Issue
3
Pages
365–376
Identifiers
DOI: 10.1007/s00775-019-01653-6
Source
Springer Nature
Keywords
License
Yellow

Abstract

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

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