A novel platinum complex of the histone deacetylase inhibitor belinostat: Rational design, development and in vitro cytotoxicity
Author | Parker, James P. |
Author | Nimir, Hassan |
Author | Griffith, Darren M. |
Author | Duff, Brian |
Author | Chubb, Anthony J. |
Author | Brennan, Marian P. |
Author | Morgan, Maria P. |
Author | Egan, Denise A. |
Author | Marmion, Celine J. |
Available date | 2015-11-15T10:42:59Z |
Publication Date | 2013-03 |
Publication Name | Journal of Inorganic Biochemistry |
Identifier | http://dx.doi.org/10.1016/j.jinorgbio.2013.03.011 |
Citation | Parker, J., Nimir, H., Griffith, D. , et. al. (2013) ,"A novel platinum complex of the histone deacetylase inhibitor belinostat: Rational design, development and in vitro cytotoxicity", 124:70-77 |
ISSN | 0162-0134 |
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. |
Sponsor | Science Foundation Ireland Grant Nos. [08/RFP/CHE1675] and [11/RFP.1/CHS/3095]. Programme for Research in Third Level Institutions (PRTLI), administered by the HEA for funding and the Technological Sector Research, Strand III (2006–2010). |
Language | en |
Publisher | Elsevier Inc. |
Subject | Platinum Histone deacetylases Histone deacetylase inhibitors Belinostat Anti-cancer Cytotoxicity |
Type | Article |
Pagination | 70-77 |
Volume Number | 124 |
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