Novel Spirooxindole-Benzofuran Scaffold: Potential Inhibition Against Hepatocellular Carcinoma by Targeting MDM2-p53 Interaction
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F24%3A73634046" target="_blank" >RIV/61989592:15110/24:73634046 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/61989592:15640/24:73634046
Výsledek na webu
<a href="https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/slct.202403953" target="_blank" >https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/slct.202403953</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/slct.202403953" target="_blank" >10.1002/slct.202403953</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Novel Spirooxindole-Benzofuran Scaffold: Potential Inhibition Against Hepatocellular Carcinoma by Targeting MDM2-p53 Interaction
Popis výsledku v původním jazyce
We synthesized a novel compound library featuring a spirooxindole core structure combined with various heterocycles, including benzofuran, benzothiophene, and thiophene scaffolds. Evaluation using MTT assays against HepG2, 4T1, and MDA-MB-231 cells revealed the most potent candidate, spirooxindole hybrid 5c, with an IC50 of 5 +/- 0.6 mu M against HepG2, inducing G2/M phase cell cycle arrest, inhibition of the wound healing, and induction of ROS. Selected spirooxindole conjugates exhibited significant inhibitory potential against MDM2, with KD values ranging from 0.0531 to 16.8 mu M. Notably, the salt of spirooxindole analogue 5q demonstrated the highest inhibitory activity at KD = 53.1 nM. Molecular docking studies revealed excellent accommodation of the designed compounds within the MDM2 receptor. All compounds displayed favorable ADME profiles, suggesting their potential as lead compounds for further optimization.
Název v anglickém jazyce
Novel Spirooxindole-Benzofuran Scaffold: Potential Inhibition Against Hepatocellular Carcinoma by Targeting MDM2-p53 Interaction
Popis výsledku anglicky
We synthesized a novel compound library featuring a spirooxindole core structure combined with various heterocycles, including benzofuran, benzothiophene, and thiophene scaffolds. Evaluation using MTT assays against HepG2, 4T1, and MDA-MB-231 cells revealed the most potent candidate, spirooxindole hybrid 5c, with an IC50 of 5 +/- 0.6 mu M against HepG2, inducing G2/M phase cell cycle arrest, inhibition of the wound healing, and induction of ROS. Selected spirooxindole conjugates exhibited significant inhibitory potential against MDM2, with KD values ranging from 0.0531 to 16.8 mu M. Notably, the salt of spirooxindole analogue 5q demonstrated the highest inhibitory activity at KD = 53.1 nM. Molecular docking studies revealed excellent accommodation of the designed compounds within the MDM2 receptor. All compounds displayed favorable ADME profiles, suggesting their potential as lead compounds for further optimization.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30107 - Medicinal chemistry
Návaznosti výsledku
Projekt
<a href="/cs/project/LX22NPO5102" target="_blank" >LX22NPO5102: Národní ústav pro výzkum rakoviny</a><br>
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2024
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
ChemistrySelect
ISSN
2365-6549
e-ISSN
—
Svazek periodika
9
Číslo periodika v rámci svazku
46
Stát vydavatele periodika
DE - Spolková republika Německo
Počet stran výsledku
13
Strana od-do
nestránkováno
Kód UT WoS článku
001371028400001
EID výsledku v databázi Scopus
2-s2.0-85211205548