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

0435475 - BFÚ 2015 RIV US eng J - Článek v odborném periodiku
Novohradský, Vojtěch - Zerzánková, Lenka - Štěpánková, Jana - Vrána, Oldřich - Raveendran, R. - Gibson, D. - Kašpárková, Jana - Brabec, Viktor
Antitumor platinum(IV) derivatives of oxaliplatin with axial valproato ligands.
Journal of Inorganic Biochemistry. Roč. 140, NOV2014 (2014), s. 72-79. ISSN 0162-0134. E-ISSN 1873-3344
Grant CEP: GA ČR(CZ) GA14-21053S
Institucionální podpora: RVO:68081707
Klíčová slova: Platinum(IV) prodrugs * Anticancer * Histone deacetylase
Kód oboru RIV: BO - Biofyzika
Impakt faktor: 3.444, rok: 2014

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. (C) 2014 Elsevier Inc. All rights reserved.
Trvalý link: http://hdl.handle.net/11104/0239852