Click estradiol dimers with novel aromatic bridging units: synthesis and anticancer evaluation.

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00587162" target="_blank" >RIV/61388963:_____/24:00587162 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378050:_____/24:00587162 RIV/61989592:15110/24:73625419 RIV/60461373:22330/24:43930222 RIV/00098892:_____/24:10158703

Výsledek na webu

<a href="https://www.tandfonline.com/doi/full/10.1080/14756366.2024.2367139" target="_blank" >https://www.tandfonline.com/doi/full/10.1080/14756366.2024.2367139</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/14756366.2024.2367139" target="_blank" >10.1080/14756366.2024.2367139</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Click estradiol dimers with novel aromatic bridging units: synthesis and anticancer evaluation.

Popis výsledku v původním jazyce

Estradiol dimers (EDs) possess significant anticancer activity by targeting tubulin dynamics. In this study, we synthesised 12 EDs variants via copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction, focusing on structural modifications within the aromatic bridge connecting two estradiol moieties. In vitro testing of these EDs revealed a marked improvement in selectivity towards cancerous cells, particularly for ED1-8. The most active compounds, ED3 (IC50=0.38muM in CCRF-CEM) and ED5 (IC50=0.71muM in CCRF-CEM) demonstrated cytotoxic effects superior to 2-methoxyestradiol (IC50=1.61muM in CCRF-CEM) and exhibited anti-angiogenic properties in an endothelial cell tube-formation model. Cell-based experiments and in vitro assays revealed that EDs interfere with mitotic spindle assembly. Additionally, we proposed an in silico model illustrating the probable binding modes of ED3 and ED5, suggesting that dimers with a simple linker and a single substituent on the aromatic central ring possess enhanced characteristics compared to more complex dimers.

Název v anglickém jazyce

Click estradiol dimers with novel aromatic bridging units: synthesis and anticancer evaluation.

Popis výsledku anglicky

Estradiol dimers (EDs) possess significant anticancer activity by targeting tubulin dynamics. In this study, we synthesised 12 EDs variants via copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction, focusing on structural modifications within the aromatic bridge connecting two estradiol moieties. In vitro testing of these EDs revealed a marked improvement in selectivity towards cancerous cells, particularly for ED1-8. The most active compounds, ED3 (IC50=0.38muM in CCRF-CEM) and ED5 (IC50=0.71muM in CCRF-CEM) demonstrated cytotoxic effects superior to 2-methoxyestradiol (IC50=1.61muM in CCRF-CEM) and exhibited anti-angiogenic properties in an endothelial cell tube-formation model. Cell-based experiments and in vitro assays revealed that EDs interfere with mitotic spindle assembly. Additionally, we proposed an in silico model illustrating the probable binding modes of ED3 and ED5, suggesting that dimers with a simple linker and a single substituent on the aromatic central ring possess enhanced characteristics compared to more complex dimers.

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

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Journal of Enzyme Inhibition and Medicinal Chemistry

ISSN

1475-6366

e-ISSN

1475-6374

Svazek periodika

39

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

15

Strana od-do

2367139

Kód UT WoS článku

001252432600001

EID výsledku v databázi Scopus

2-s2.0-85196514008