Antiproliferative, DNA binding, and cleavage properties of dinuclear Co(III) complexes containing the bioactive quinizarin ligand

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F20%3A00524188" target="_blank" >RIV/68081707:_____/20:00524188 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/20:73603672

Výsledek na webu

<a href="https://link.springer.com/article/10.1007/s00775-020-01765-4" target="_blank" >https://link.springer.com/article/10.1007/s00775-020-01765-4</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00775-020-01765-4" target="_blank" >10.1007/s00775-020-01765-4</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Antiproliferative, DNA binding, and cleavage properties of dinuclear Co(III) complexes containing the bioactive quinizarin ligand

Popis výsledku v původním jazyce

The adverse side effects and acquired resistance associated with the clinical application of traditional platinum-based anticancer drugs have forced investigation of alternative transition metal-based compounds and their cytostatic properties. Over the last years, the anticancer potential of cobalt complexes has been extensively studied, and in-depth analyses of their mode of action have been conducted. In this work, we present antiproliferative activity against human cancer cells of the dinuclear Co(III) complexes bearing the quinizarin ligand and tris(2-aminoethyl)amine (tren, compound 1) or tris(2-pyridylmethyl)amine (tpa, compound 2) co-ligands. To contribute the understanding mechanisms of biological action of these compounds, their association with DNA in the cells, DNA binding in cell-free media, and DNA cleavage capability were investigated in detail. The results demonstrate that both complexes interact with DNA in tumor cells. However, their mechanism of antiproliferative action is different, and this difference is mirrored by distinct antiproliferative activity. The antiproliferative effect of 1 is connected with its ability to intercalate into DNA and subsequently to inhibit activities of DNA processing enzymes. In contrast, the total antiproliferative efficiency of 2, thanks to its redox properties, appears to be connected with its ability to form radicals and, consequently, with the ability of 2 to cleave DNA. Hence, the findings presented in this study may significantly contribute to understanding the antitumor potential of cobalt complexes.

Název v anglickém jazyce

Antiproliferative, DNA binding, and cleavage properties of dinuclear Co(III) complexes containing the bioactive quinizarin ligand

Popis výsledku anglicky

The adverse side effects and acquired resistance associated with the clinical application of traditional platinum-based anticancer drugs have forced investigation of alternative transition metal-based compounds and their cytostatic properties. Over the last years, the anticancer potential of cobalt complexes has been extensively studied, and in-depth analyses of their mode of action have been conducted. In this work, we present antiproliferative activity against human cancer cells of the dinuclear Co(III) complexes bearing the quinizarin ligand and tris(2-aminoethyl)amine (tren, compound 1) or tris(2-pyridylmethyl)amine (tpa, compound 2) co-ligands. To contribute the understanding mechanisms of biological action of these compounds, their association with DNA in the cells, DNA binding in cell-free media, and DNA cleavage capability were investigated in detail. The results demonstrate that both complexes interact with DNA in tumor cells. However, their mechanism of antiproliferative action is different, and this difference is mirrored by distinct antiproliferative activity. The antiproliferative effect of 1 is connected with its ability to intercalate into DNA and subsequently to inhibit activities of DNA processing enzymes. In contrast, the total antiproliferative efficiency of 2, thanks to its redox properties, appears to be connected with its ability to form radicals and, consequently, with the ability of 2 to cleave DNA. Hence, the findings presented in this study may significantly contribute to understanding the antitumor potential of cobalt complexes.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GA18-09502S" target="_blank" >GA18-09502S: Ovlivnění rezistence nádorových buněk k chemoterapii s cílem obnovit jejich citlivost k novým, existujícím a dosud neúspěšným metalofarmakům</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

Journal of Biological Inorganic Chemistry

ISSN

0949-8257

e-ISSN

—

Svazek periodika

25

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

12

Strana od-do

339-350

Kód UT WoS článku

000517028300002

EID výsledku v databázi Scopus

2-s2.0-85081028160