Antitumor platinum(IV) derivatives of oxaliplatin with axial valproato ligands
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
25063910
DOI
10.1016/j.jinorgbio.2014.07.004
PII: S0162-0134(14)00194-9
Knihovny.cz E-zdroje
- Klíčová slova
- Anticancer, Dual targeting, Histone deacetylase, Oxaliplatin, Platinum(IV) prodrugs, Valproic acid,
- MeSH
- inhibitory histondeacetylas chemie farmakologie MeSH
- lidé MeSH
- ligandy MeSH
- magnetická rezonanční spektroskopie MeSH
- nádorové buněčné linie MeSH
- organoplatinové sloučeniny chemie farmakologie MeSH
- oxaliplatin MeSH
- protinádorové látky chemie farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- inhibitory histondeacetylas MeSH
- ligandy MeSH
- organoplatinové sloučeniny MeSH
- oxaliplatin MeSH
- protinádorové látky 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.
Citace poskytuje Crossref.org
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