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


    Pinheiro Araujo, Thaylan and Gandin, Valentina and Kavanagh, Paul and Braude, Jeremy Philip and Nodari, Luca and Montagner, Diego and Erxleben, Andrea (2016) DNA binding, cleavage and cytotoxicity of a novel dimetallic Fe(III) triaza-cyclononane complex. Inorganica Chimica Acta, 142. pp. 170-175. ISSN 0020-1693

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    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).

    Item Type: Article
    Keywords: Iron(III); DNA cleavage; DNA binding; Cytotoxicity;
    Academic Unit: Faculty of Science and Engineering > Chemistry
    Item ID: 12584
    Identification Number: https://doi.org/10.1016/j.ica.2016.02.044
    Depositing User: Diego Montagner
    Date Deposited: 23 Mar 2020 12:06
    Journal or Publication Title: Inorganica Chimica Acta
    Publisher: Elsevier
    Refereed: Yes
    URI:

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