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.
CommentsNOTICE: this is the author’s version of a work that was accepted for publication in Journal of Inorganic Biochemistry. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Inorganic Biochemistry. 2013;124:70-7. DOI 10.1016/j.jinorgbio.2013.03.011 http://www.sciencedirect.com/science/article/pii/S016201341300069X
Published CitationParker JP, Nimir H, Griffith DM, Duff B, Chubb AJ, Brennan MP, Morgan MP, Egan DA, Marmion CJ. A novel platinum complex of the histone deacetylase inhibitor belinostat: rational design, development and in vitro cytotoxicity. Journal of Inorganic Biochemistry. 2013;124:70-7.
- School of Pharmacy and Biomolecular Sciences