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

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. (C) 2013 Elsevier Inc. All rights reserved.