Identification of Eukaryotic Translation Elongation Factor 1-alpha 1 Gamendazole-Binding Site for Binding of 3-Hydroxy-4(1&ITH&IT)-quinolinones as Novel Ligands with Anticancer Activity

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F18%3A10375275" target="_blank" >RIV/00216208:11130/18:10375275 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1021/acs.jmedchem.8b00078" target="_blank" >https://doi.org/10.1021/acs.jmedchem.8b00078</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jmedchem.8b00078" target="_blank" >10.1021/acs.jmedchem.8b00078</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Identification of Eukaryotic Translation Elongation Factor 1-alpha 1 Gamendazole-Binding Site for Binding of 3-Hydroxy-4(1&ITH&IT)-quinolinones as Novel Ligands with Anticancer Activity

Popis výsledku v původním jazyce

Here, we have identified the interaction site of the contraceptive drug gamendazole using computational modeling. The drug was previously described as a ligand for eukaryotic translation elongation factor 1-alpha 1 (eEF1A1) and found to be a potential target site for derivatives of 2-phenyl-3-hydroxy-4(1H)-quinolinones (3-HQs), which exhibit anticancer activity. The interaction of this class of derivatives of 3-HQs with eEF1A1 inside cancer cells was confirmed via pull-down assay. We designed and synthesized a new family of 3-HQs and subsequently applied isothermal titration calorimetry to show that these compounds strongly bind to eEF1A1. Further, we found that some of these derivatives possess significant in vitro anticancer activity.

Název v anglickém jazyce

Identification of Eukaryotic Translation Elongation Factor 1-alpha 1 Gamendazole-Binding Site for Binding of 3-Hydroxy-4(1&ITH&IT)-quinolinones as Novel Ligands with Anticancer Activity

Popis výsledku anglicky

Here, we have identified the interaction site of the contraceptive drug gamendazole using computational modeling. The drug was previously described as a ligand for eukaryotic translation elongation factor 1-alpha 1 (eEF1A1) and found to be a potential target site for derivatives of 2-phenyl-3-hydroxy-4(1H)-quinolinones (3-HQs), which exhibit anticancer activity. The interaction of this class of derivatives of 3-HQs with eEF1A1 inside cancer cells was confirmed via pull-down assay. We designed and synthesized a new family of 3-HQs and subsequently applied isothermal titration calorimetry to show that these compounds strongly bind to eEF1A1. Further, we found that some of these derivatives possess significant in vitro anticancer activity.

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

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Journal of Medicinal Chemistry

ISSN

0022-2623

e-ISSN

—

Svazek periodika

61

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

3027-3036

Kód UT WoS článku

000430256600026

EID výsledku v databázi Scopus

2-s2.0-85045569345