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

نویسندگان

  • James P Parker
  • Hassan Nimir
  • Darren M Griffith
  • Brian Duff
  • Anthony J Chubb
  • Marian P Brennan
  • Maria P Morgan
  • Denise A Egan
  • Celine J Marmion
چکیده

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-[Pt(II)(NH3)2(malSAHA-2H)] and (iii) favourable cyto-selective properties as compared to cisplatin and belinostat.

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عنوان ژورنال:
  • Journal of inorganic biochemistry

دوره 124  شماره 

صفحات  -

تاریخ انتشار 2013