Anticancer kiteplatin pyrophosphate derivatives show unexpected target selectivity for DNA

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F17%3A00486058" target="_blank" >RIV/68081707:_____/17:00486058 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/17:73583752

Výsledek na webu

<a href="http://dx.doi.org/10.1039/c7dt02633a" target="_blank" >http://dx.doi.org/10.1039/c7dt02633a</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/c7dt02633a" target="_blank" >10.1039/c7dt02633a</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Anticancer kiteplatin pyrophosphate derivatives show unexpected target selectivity for DNA

Popis výsledku v původním jazyce

One of the promising new antitumor platinum complexes is a large-ring chelate complex [PtCl2(cis-1,4-DACH)] (DACH = diaminocyclohexane) (kiteplatin). Recently, new platinum(II) derivatives of kiteplatin with pyrophosphate as a carrier ligand have been synthesized and tested on a panel of human cancer cell lines. These derivatives of kiteplatin were found to be more effective than clinically used anticancer platinum drugs. The design of kiteplatin pyrophosphate derivatives was based on the concept of pyrophosphate coordinated platinum complexes, phosphaplatins. Phosphaplatins have been shown to function without binding to DNA and hence DNA has been excluded as the target of phosphaplatins in contrast to conventional antitumor platinum drugs. Cytotoxicity, major cellular targets and DNA interactions of the new anticancer platinum drug were characterized by standard biochemical methods and methods of molecular and cellular biology. We demonstrate that, in contrast to what has been reported on closely related phosphaplatins, the derivatives of kiteplatin with the pyrophosphate carrier ligand are activated in the cellular environment. This activation, which yields species capable of platination of DNA, very likely comprises the hydrolytic release of the pyrophosphate ligand that could be enzymatically catalyzed. Collectively, these data provide convincing evidence that unexpectedly DNA is an important target for the biological activity of the kiteplatin pyrophosphate derivatives, although the overall mechanism of action might be different from those of conventional platinum drugs.

Název v anglickém jazyce

Anticancer kiteplatin pyrophosphate derivatives show unexpected target selectivity for DNA

Popis výsledku anglicky

One of the promising new antitumor platinum complexes is a large-ring chelate complex [PtCl2(cis-1,4-DACH)] (DACH = diaminocyclohexane) (kiteplatin). Recently, new platinum(II) derivatives of kiteplatin with pyrophosphate as a carrier ligand have been synthesized and tested on a panel of human cancer cell lines. These derivatives of kiteplatin were found to be more effective than clinically used anticancer platinum drugs. The design of kiteplatin pyrophosphate derivatives was based on the concept of pyrophosphate coordinated platinum complexes, phosphaplatins. Phosphaplatins have been shown to function without binding to DNA and hence DNA has been excluded as the target of phosphaplatins in contrast to conventional antitumor platinum drugs. Cytotoxicity, major cellular targets and DNA interactions of the new anticancer platinum drug were characterized by standard biochemical methods and methods of molecular and cellular biology. We demonstrate that, in contrast to what has been reported on closely related phosphaplatins, the derivatives of kiteplatin with the pyrophosphate carrier ligand are activated in the cellular environment. This activation, which yields species capable of platination of DNA, very likely comprises the hydrolytic release of the pyrophosphate ligand that could be enzymatically catalyzed. Collectively, these data provide convincing evidence that unexpectedly DNA is an important target for the biological activity of the kiteplatin pyrophosphate derivatives, although the overall mechanism of action might be different from those of conventional platinum drugs.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Dalton Transactions

ISSN

1477-9226

e-ISSN

—

Svazek periodika

46

Číslo periodika v rámci svazku

41

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

14139-14148

Kód UT WoS článku

000413638400011

EID výsledku v databázi Scopus

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