Peer-Reviewed Journal Details
Mandatory Fields
Griffith, DM;Duff, B;Suponitsky, KY;Kavanagh, K;Morgan, MP;Egan, D;Marmion, CJ
2011
June
Journal of Inorganic Biochemistry
Novel trans-platinum complexes of the histone deacetylase inhibitor valproic acid; synthesis, in vitro cytotoxicity and mutagenicity
Published
37 ()
Optional Fields
OVARIAN-CANCER CELLS ANTICANCER DRUGS ANTITUMOR COMPLEXES DONOR SETS CARBOPLATIN HYDROLYSIS CISPLATIN THERAPY AGENT MECHANISM
105
793
799
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)(2)] 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. (C) 2011 Elsevier Inc. All rights reserved.
NEW YORK
0162-0134
10.1016/j.jinorgbio.2011.03.001
Grant Details