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    Phosphate Diester Cleavage, DNA Interaction and Cytotoxic Activity of a Bimetallic Bis(1,4,7-triazacyclononane) Zinc Complex


    Montagner, Diego and Gandin, Valentina and Marzano, Cristina and Erxleben, Andrea (2014) Phosphate Diester Cleavage, DNA Interaction and Cytotoxic Activity of a Bimetallic Bis(1,4,7-triazacyclononane) Zinc Complex. European Journal of Inorganic Chemistry, 2014 (25). pp. 4084-4092. ISSN 1434-1948

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    Abstract

    The dinuclear zinc complex [Zn2{bcmp(-H)}(μ-Cl)](ClO4)2· H2O {bcmp = 2,6-bis(1,4,7-triazacyclonon-1-ylmethyl)-4- methylphenol} has been synthesized and structurally characterized. The DNA binding affinity was assessed by ethidium bromide fluorescence quenching experiments. The complex relaxes supercoiled pUC19 DNA into the nicked form at low micromolar concentration. Mechanistic studies were carried out using the DNA and RNA models bis(2,4-dinitrophenyl) phosphate (BDNPP) and 2-hydroxypropyl p-nitrophenyl phosphate (HPNP). A detailed kinetic analysis suggested that the bridging OH group of the solution species [Zn2{bcmp(-H)}(μ-OH)]2+ acts as the nucleophile in the hydrolysis of BDNPP, while in the case of HPNP, the bridging OH group acts as a general base and seems to shift to a terminal position upon substrate coordination. Finally, the cytotoxicity profile of the dinuclear zinc(II) complex was assessed. The complex showed promising in vitro antitumour activity against pancreatic and lung cancers cell lines.

    Item Type: Article
    Keywords: Drug design; Antitumor agents; Cytotoxicity; Zinc; DNA; DNA cleavage;
    Academic Unit: Faculty of Science and Engineering > Chemistry
    Item ID: 7816
    Identification Number: https://doi.org/10.1002/ejic.201402319
    Depositing User: Diego Montagner
    Date Deposited: 26 Jan 2017 16:47
    Journal or Publication Title: European Journal of Inorganic Chemistry
    Publisher: Wiley
    Refereed: Yes
    Funders: European Commission, Science Foundation Ireland (SFI)
    URI:

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