Antitumor platinum(IV) derivatives of oxaliplatin with axial valproato ligands
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
25063910
DOI
10.1016/j.jinorgbio.2014.07.004
PII: S0162-0134(14)00194-9
Knihovny.cz E-resources
- Keywords
- Anticancer, Dual targeting, Histone deacetylase, Oxaliplatin, Platinum(IV) prodrugs, Valproic acid,
- MeSH
- Histone Deacetylase Inhibitors chemistry pharmacology MeSH
- Humans MeSH
- Ligands MeSH
- Magnetic Resonance Spectroscopy MeSH
- Cell Line, Tumor MeSH
- Organoplatinum Compounds chemistry pharmacology MeSH
- Oxaliplatin MeSH
- Antineoplastic Agents chemistry pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Histone Deacetylase Inhibitors MeSH
- Ligands MeSH
- Organoplatinum Compounds MeSH
- Oxaliplatin MeSH
- Antineoplastic Agents MeSH
We report new anticancer prodrugs, platinum(IV) derivatives of oxaliplatin conjugated with valproic acid (VPA), a well-known drug having histone deacetylase inhibitory activity. Like most platinum(IV) derivatives, the cytotoxicity of the conjugates was lower in cell culture than that of oxaliplatin, but greater than those of its Pt(IV) derivative containing biologically inactive axial ligands in several cancer cell lines. Notably, these conjugates display activity in both cisplatin sensitive- and resistant tumor cells capable of both markedly enhanced accumulation in tumor cells and acting in a dual threat manner, concurrently targeting histone deacetylase and genomic DNA. These results demonstrate the dual targeting strategy to be a valuable route to pursue in the design of platinum agents which may be more effective in cancer types that are typically resistant to therapy by conventional cisplatin. Moreover, platinum(IV) derivatives containing VPA axial ligands seem to be promising dual-targeting candidates for additional preclinical studies.
References provided by Crossref.org
Epigenetic and antitumor effects of platinum(IV)-octanoato conjugates
