A novel platinum complex of the histone deacetylase inhibitor belinostat: Rational design, development and in vitro cytotoxicity
عرض / فتح
التاريخ
2013-03المؤلف
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.
...show more authors ...show less authors
البيانات الوصفية
عرض كامل للتسجيلةالملخص
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.
المجموعات
- الكيمياء وعلوم الأرض [557 items ]