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    A novel platinum complex of the histone deacetylase inhibitor belinostat: Rational design, development and in vitro cytotoxicity

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    Date
    2013-03
    Author
    Parker, James P.
    Nimir, Hassan
    Griffith, Darren M.
    Duff, Brian
    Chubb, Anthony J.
    Brennan, Marian P.
    Morgan, Maria P.
    Egan, Denise A.
    Marmion, Celine J.
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    Abstract
    The successful design and synthesis of a novel Pt complex of the histone deacteylase inhibitor belinostat are reported. Molecular modelling assisted in the identification of a suitable malonate derivative of belinostat(mal-p-Bel) for complexation to platinum. Reaction of [Pt(NH3)2(H2O)2](NO3)2 with the disodium salt of mal-p-Bel gave cis-[Pt(NH3)2(mal-p-Bel-2H)] (where -2H indicates that mal-p-Bel is doubly deprotonated) in excellent yield. An in vitro cytotoxicity study revealed that cis-[Pt(NH3)2(mal-p-Bel-2H)] possesses (i) considerable cytotoxicity against reported ovarian cancer cell lines, (ii) enhanced cytotoxicity relative to the previously reported Pt histone deacetylase inhibitor conjugate, cis-[PtII(NH3)2(malSAHA-2H)] and (iii) favourable cyto-selective properties as compared to cisplatin and belinostat.
    DOI/handle
    http://dx.doi.org/10.1016/j.jinorgbio.2013.03.011
    http://hdl.handle.net/10576/3818
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    • Chemistry & Earth Sciences [‎614‎ items ]

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