Valuable Insight into the Anticancer Activity of the Platinum-Histone Deacetylase Inhibitor Conjugate, cis-[Pt(NH3)2malSAHA–2H)]

cis-[PtII(NH3)2(malSAHA–2H)], a cisplatin adduct conjugated to a potent histone deacetylase inhibitor (HDACi), suberoylanilide hydroxamic acid (SAHA), was previously developed as a potential anticancer agent. This Pt–HDACi conjugate was demonstrated to have comparable cytotoxicity to cisplatin against A2780 ovarian cancer cells but significantly reduced cytotoxicity against a representative normal cell line, NHDF. Thus, with a view to (i) understanding more deeply the effects that may play an important role in the biological (pharmacological) properties of this new conjugate against cancer cells and (ii) developing the next generation of Pt–HDACi conjugates, the cytotoxicity, DNA binding, cellular accumulation and HDAC inhibitory activity of cis-[PtII(NH3)2(malSAHA–2H)] were investigated and are reported herein. cis-[PtII(NH3)2(malSAHA–2H)] was found to have marginally lower cytotoxicity against a panel of cancer cell lines as compared to cisplatin and SAHA. cis-[PtII(NH3)2(malSAHA–2H)] was also found to ...