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    Novel trans-platinum complexes of the histone deacetylase inhibitor valproic acid; synthesis, in vitro cytotoxicity and mutagenicity


    Griffith, Darren M. and Duff, Brian and Suponitsky, Kyrill Y. and Kavanagh, Kevin and Morgan, Maria P. and Egan, Denise and Marmion, Celine J. (2011) Novel trans-platinum complexes of the histone deacetylase inhibitor valproic acid; synthesis, in vitro cytotoxicity and mutagenicity. Journal of Inorganic Biochemistry, 105 (6). pp. 793-799. ISSN 0162-0134

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    Abstract

    The first examples of Pt complexes of the well known anti-epilepsy drug and histone deacetylase inhibitor, valproic acid (VPA), are reported. Reaction of the Pt(II) am(m)ine precursors trans-[PtCl2(NH3)(py)] and trans-[PtCl2(py)2] with silver nitrate and subsequently sodium valproate gave trans-[Pt(VPA−1H)2(NH3)(py)] and trans-[Pt(VPA−1H)2(py)2], respectively. The valproato ligands in both complexes are bound to the Pt(II) centres via the carboxylato functionality and in a monodentate manner. The X-ray crystal structure of trans- [Pt(VPA−1H)2(NH3)(py)] is described. Replacement of the dichlorido ligands in trans-[PtCl2(py)2] and trans- [PtCl2(NH3)(py)] by valproato ligands (VPA−1H) to yield trans-[Pt(VPA−1H)2(py)2] and trans-[Pt(VPA−1H)2 (NH3)(py)] respectively, significantly enhanced cytotoxicity against A2780 (parental) and A2780 cisR (cisplatin resistant) ovarian cancer cells. The mutagenicity of trans-[Pt(VPA−1H)2(NH3)(py)] and trans-[Pt (VPA−1H)2(py)2] was determined using the Ames test and is also reported.

    Item Type: Article
    Additional Information: The definitive version of this article is available at doi:10.1016/j.jinorgbio.2011.03.001
    Keywords: Trans-Pt complexes; Histone deactylase inhibitor; Valproic acid; Cytotoxicity; Mutagenicity;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 4223
    Depositing User: Dr. Kevin Kavanagh
    Date Deposited: 26 Feb 2013 16:06
    Journal or Publication Title: Journal of Inorganic Biochemistry
    Publisher: Elsevier
    Refereed: Yes
    URI:

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