An Anticancer Pt-IV Prodrug That Acts by Mechanisms Involving DNA Damage and Different Epigenetic Effects

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F19%3A00510854" target="_blank" >RIV/68081707:_____/19:00510854 - isvavai.cz</a>

Result on the web

<a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.201805626" target="_blank" >https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.201805626</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/chem.201805626" target="_blank" >10.1002/chem.201805626</a>

Result language

angličtina

Original language name

An Anticancer Pt-IV Prodrug That Acts by Mechanisms Involving DNA Damage and Different Epigenetic Effects

Original language description

Dual- or multi-action Pt-IV prodrugs represent a new generation of platinum anticancer drugs. The important property of these Pt-IV prodrugs is that their antitumor action combines several different mechanisms owing to the presence of biologically active axial ligands. This work describes the synthesis and some biological properties of a triple-action prodrug that releases in cancer cells cisplatin and two different epigenetically acting moieties, octanoate and phenylbutyrate. It is demonstrated, with the aid of modern methods of molecular and cellular biology and pharmacology, that the presence of three different functionalities in a single molecule of the Pt-IV prodrug results in a selective and high potency in tumor cells including those resistant to cisplatin [the IC50 values in the screened malignant cell lines ranged from as low as 9nm (HCT-116) to 74nm (MDA-MB-231)]. It is also demonstrated that cellular activation of the Pt-IV prodrug results in covalent modification of DNA through the release of the platinum moiety accompanied by inhibition of the activity of histone deacetylases caused by phenylbutyrate and by global hypermethylation of DNA by octanoate. Thus, the Pt-IV prodrug introduced in this study acts as a true multi-action prodrug, which is over two orders of magnitude more active than clinically used cisplatin, in both 2D monolayer culture and 3D spheroid cancer cells.

Czech name

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Czech description

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Type

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

CEP classification

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OECD FORD branch

10406 - Analytical chemistry

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

2019

Confidentiality

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

Name of the periodical

Chemistry - A European Journal

ISSN

0947-6539

e-ISSN

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Volume of the periodical

25

Issue of the periodical within the volume

20

Country of publishing house

DE - GERMANY

Number of pages

11

Pages from-to

5235-5245

UT code for WoS article

000468855200017

EID of the result in the Scopus database

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