Anticancer kiteplatin pyrophosphate derivatives show unexpected target selectivity for DNA

Result code in 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>

Alternative codes found

RIV/61989592:15310/17:73583752

Result on the web

<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>

Result language

angličtina

Original language name

Anticancer kiteplatin pyrophosphate derivatives show unexpected target selectivity for DNA

Original language description

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.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

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

Publication year

2017

Confidentiality

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

Name of the periodical

Dalton Transactions

ISSN

1477-9226

e-ISSN

—

Volume of the periodical

46

Issue of the periodical within the volume

41

Country of publishing house

GB - UNITED KINGDOM

Number of pages

10

Pages from-to

14139-14148

UT code for WoS article

000413638400011

EID of the result in the Scopus database

—