DNA binding, cleavage and cytotoxicity of a novel dimetallic Fe(III) triaza-cyclononane complex

Thaylan Pinheiro Araujo, Valentina Gandin, Paul Kavanagh, Jeremy Phillip Braude, Luca Nodari, Diego Montagner*, Andrea Erxleben

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

A novel bimetallic Fe(III) complex with the bis(triaza-cyclononane) ligand 2,6-bis(1,4,7-triazacyclonon-1-ylmethyl)-4-methylphenol (bcmp) is reported. [Fe2{bcmp(-H)}(μ-OH)Cl2]Cl2 (2) contains two octahedral Fe(III) centers bound to the two triaza-cyclononane rings of bcmp. The coordination sphere is completed by one chlorine, one bridging phenolate oxygen and one bridging hydroxide group. The complex has been characterized by elemental analysis, Mössbauer spectroscopy, UV–Vis spectroscopy, pH potentiometric titration, ESI mass spectrometry and cyclic voltammetry. The complex hydrolyzes the DNA model bis(2,4-dinitrophenyl) phosphate (BDNPP) with a maximum activity a pH 7. Michaelis–Menten behavior is observed with kcat = 3.56 × 10−4 s−1 and Km = 0.56 mM (pH 7.0, 40 °C). The interaction of 2 with CT DNA was studied by electronic absorption spectroscopy and gel electrophoresis. Notably, the complex relaxes supercoiled pUC19 DNA into the nicked form at low micromolar concentration (10 μM) in the presence of an external reducing agent (ascorbic acid). Finally, the in vitro antiproliferative activity of 2 was assessed on a panel of human cancer cell lines and results revealed that the complex exhibited a significant cytotoxic effects in particular versus colon LoVo cancer cells, wih IC50 value 2.5 times lower than that shown by the reference metallodrug cisplatin (3.54 versus 8.53 μM).

Original languageEnglish
Pages (from-to)170-175
Number of pages6
JournalInorganica Chimica Acta
Volume452
Early online date03 Mar 2016
DOIs
Publication statusPublished - 01 Oct 2016

Keywords

  • Cytotoxicity
  • DNA binding
  • DNA cleavage
  • Iron(III)

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry
  • Materials Chemistry

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