Platinum(II)-oxalato complexes of seliciclib (CYC202) derivatives show different cellular effects and lesser adverse effects in mouse lymphoma model than cisplatin

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F20%3A73596667" target="_blank" >RIV/61989592:15310/20:73596667 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14160/20:00118186 RIV/62157124:16370/20:43877666

Result on the web

<a href="https://link.springer.com/article/10.1007%2Fs00775-019-01735-5" target="_blank" >https://link.springer.com/article/10.1007%2Fs00775-019-01735-5</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00775-019-01735-5" target="_blank" >10.1007/s00775-019-01735-5</a>

Result language

angličtina

Original language name

Platinum(II)-oxalato complexes of seliciclib (CYC202) derivatives show different cellular effects and lesser adverse effects in mouse lymphoma model than cisplatin

Original language description

This work presents a deeper pharmacological evaluation of two formerly prepared and characterized, and highly in vitro cytotoxic platinum(II) oxalato complexes [Pt(ox)(L-1)(2)] (1) and [Pt(ox)(L-2)(2)] (2), containing the derivatives of cyclin-dependent kinase inhibitor (CDKi) seliciclib ((R)-roscovitine, CYC202) coordinating as N-donor carrier ligands, i.e., 2-(1-ethyl-2-hydroxyethylamino)-N6-(4-methoxybenzyl)-9-isopropyladenine (L-1) and 2-chloro-N6-(2,4-dimethoxybenzyl)-9-isopropyladenine (L-2). The positive results of in vitro cytotoxicity screening on human cancer cell lines (HeLa, HOS, A2780, A2780R, G361 and MCF7 with IC50 at low micromolar levels) published previously, motivated us to perform extended preclinical in vitro experiments to reveal the mechanisms associated with the induction of cancer cell death. In addition, the in vivo antitumor activity was evaluated using the mouse lymphocytic leukaemia L1210 model. The obtained results revealed that complex 1 exceeds the antitumor effect of cisplatin (as for the extension of life-span of mice) and shows far less adverse effects as compared to reference drug cisplatin. The in vitro and ex vivo studies of cellular effects and molecular mechanisms of cell death induction showed that the mechanism of action of complex 1 is essentially different from that of cisplatin. The obtained results showed a possible way how to obtain antitumor active platinum(II) oxalato complexes with better therapeutic profile than contemporary used platinum-based therapeutics.

Czech name

—

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

—

OECD FORD branch

10402 - Inorganic and nuclear chemistry

Project

<a href="/en/project/LO1305" target="_blank" >LO1305: Development of the center of advanced technologies and materials</a><br>

Continuities

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

Publication year

2020

Confidentiality

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

Name of the periodical

JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY

ISSN

0949-8257

e-ISSN

—

Volume of the periodical

25

Issue of the periodical within the volume

1

Country of publishing house

DE - GERMANY

Number of pages

7

Pages from-to

67-73

UT code for WoS article

000493478200001

EID of the result in the Scopus database

2-s2.0-85074702029