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

KAYA B., Yilmaz Z. K., ŞAHİN O., ASLIM B., Tukenmez U., ÜLKÜSEVEN B.

JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY, cilt.24, sa.3, ss.365-376, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 24 Sayı: 3
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1007/s00775-019-01653-6
  • Dergi Adı: JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.365-376
  • Anahtar Kelimeler: Thiosemicarbazone, Iron, Manganese, DNA binding, DNA cleavage, Anti-proliferation, LIGAND COPPER(II) COMPLEXES, PBR322 PLASMID CLEAVAGE, METAL-COMPLEXES, NICKEL(II) COMPLEXES, MOLECULAR DOCKING, ZN(II) COMPLEXES, CYCLE ARREST, CYTOTOXICITY, CRYSTAL, THIOSEMICARBAZONES
  • Gazi Üniversitesi Adresli: Evet

Özet

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 mu M 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.