Antitumor platinum(IV) derivatives of oxaliplatin with axial valproato ligands.

Abstract:

: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.

journal_name

J Inorg Biochem

authors

Novohradsky V,Zerzankova L,Stepankova J,Vrana O,Raveendran R,Gibson D,Kasparkova J,Brabec V

doi

10.1016/j.jinorgbio.2014.07.004

subject

Has Abstract

pub_date

2014-11-01 00:00:00

pages

72-9

eissn

0162-0134

issn

1873-3344

pii

S0162-0134(14)00194-9

journal_volume

140

pub_type

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