A novel anti-cancer bifunctional platinum drug candidate with dual DNA binding and histone deacetylase inhibitory activity

Abstract

MP, Marmion CJ. A novel anti-cancer bifunctional platinum drug candidate with dual DNA binding and histone deacetylase inhibitory activity. Chem Commun (Camb). 2009;44:6735-6737

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

“…2-(4-Amino-benzyl)-malonic acid dimethyl ester [5] and iodoplatin [20] were synthesized as previously reported.…”

“…[1,4] We are interested in combining platinum compounds with histone deacetylase (HDAC) inhibitors (HDACIs) so as to target a broader spectrum of human cancers than clinically used Pt drugs. [5][6][7] Histones are the main protein component of chromatin, around which DNA coils. HDACs are a class of zinc metalloenzymes that deacetylate core histone lysine residues, which results in a condensed chromatin structure and ultimately transcriptional repression.…”

Novel trans-platinum complexes of the histone deacetylase inhibitor valproic acid; synthesis, in vitro cytotoxicity and mutagenicity

“…We are interested in combining platinum compounds with molecularly targeted anti-cancer drugs, particularly histone deacetylase (HDAC) inhibitors (HDACIs) [15,16]. Histones are the main protein component of chromatin, around which DNA coils.…”

“…In doing so we developed a novel anti-cancer bifunctional Pt drug candidate with dual DNA binding and HDAC inhibitory activity, cis-[Pt(NH 3 ) 2 (malSAHA −2H )] (Fig. 3) [15].…”

“…Given our interest in Pt complexes [15,[27][28][29][30] and HDAC inhibitors [15,16,31], and the emergence of the TPA complexes with the N 2 O 2 donor set [8], we sought to develop novel TPA complexes of VPA. We speculated that VPA would enhance the activity of TPA complexes as anti-cancer agents and in doing so target a broader spectrum of human cancers than clinically used Pt drugs.…”