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    In vitro anti-tumour effect of 1,10-phenanthroline-5,6-dione (phendione), [Cu(phendione)3](ClO4)2·4H2O and [Ag(phendione)2]ClO4 using human epithelial cell lines.

    Deegan, Carol and Coyle, Barry and McCann, Malachy and Devereux, Michael and Egan, Denise A. (2006) In vitro anti-tumour effect of 1,10-phenanthroline-5,6-dione (phendione), [Cu(phendione)3](ClO4)2·4H2O and [Ag(phendione)2]ClO4 using human epithelial cell lines. Chemico-Biological Interactions, 164 (1-2). pp. 115-125.

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    The anti-cancer chemotherapeutic potential of 1,10-phenanthroline-5,6-dione (phendione), [Cu(phendione)3](ClO4)2·4H2O and [Ag(phendione)2]ClO4 were determined using four human cells lines, i.e. two neoplastic (A-498 and Hep-G2) and two non-neoplastic (CHANG and HK-2). All of the phendione derivatives induced a concentration-dependant decrease in the viability of the four cell lines, with [Cu(phendione)3](ClO4)2·4H2O displaying greatest activity. In comparative studies, IC50 values obtained with the two neoplastic cell lines showed a cytotoxic response which was between 3 and 35 times greater than that observed for the metal-based anti-cancer agent, cisplatin. Furthermore, metal–phendione complexes, rather than simple solvated metal ions, were responsible for the observed cytotoxicity. Despite the high level of potency associated with these compounds they did not display an apparent cyto-selective profile, as they reduced the viability of both neoplastic and non-neoplastic cells. However, selected mechanistic studies showed that phendione and its metal complexes inhibited DNA synthesis which did not appear to be mediated through intercalation. Ames testing highlighted that all three compounds and their phase I metabolites were non-mutagenic, unlike cisplatin. Taken together, these results suggest that phendione and its Cu(II) and Ag(I) complexes may be capable of acting as highly effective anti-cancer therapies, which with careful administration could provide very potent and effective alternatives to cisplatin.

    Item Type: Article
    Keywords: 1,10-Phenanthroline-5,6-dione; Transitional metal complexes; DNA inhibition; Anti-cancer potential;
    Academic Unit: Faculty of Science and Engineering > Chemistry
    Item ID: 9716
    Depositing User: Dr. Malachy McCann
    Date Deposited: 26 Jul 2018 13:31
    Journal or Publication Title: Chemico-Biological Interactions
    Publisher: Elsevier
    Refereed: Yes
      Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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