Novel Spirooxindole-Benzofuran Scaffold: Potential Inhibition Against Hepatocellular Carcinoma by Targeting MDM2-p53 Interaction
The result's identifiers
Result code in 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>
Alternative codes found
RIV/61989592:15640/24:73634046
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Novel Spirooxindole-Benzofuran Scaffold: Potential Inhibition Against Hepatocellular Carcinoma by Targeting MDM2-p53 Interaction
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30107 - Medicinal chemistry
Result continuities
Project
<a href="/en/project/LX22NPO5102" target="_blank" >LX22NPO5102: National institute for cancer research</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
ChemistrySelect
ISSN
2365-6549
e-ISSN
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Volume of the periodical
9
Issue of the periodical within the volume
46
Country of publishing house
DE - GERMANY
Number of pages
13
Pages from-to
nestránkováno
UT code for WoS article
001371028400001
EID of the result in the Scopus database
2-s2.0-85211205548