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:	http://www.journals.elsevier.com/journal...
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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