Activation of p53 signaling and regression of breast and prostate carcinoma cells by spirooxindole-benzimidazole small molecules

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F24%3A73624946" target="_blank" >RIV/61989592:15110/24:73624946 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15640/24:73624946

Result on the web

<a href="https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1358089/full" target="_blank" >https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1358089/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fphar.2024.1358089" target="_blank" >10.3389/fphar.2024.1358089</a>

Result language

angličtina

Original language name

Activation of p53 signaling and regression of breast and prostate carcinoma cells by spirooxindole-benzimidazole small molecules

Original language description

This study discusses the synthesis and use of a new library of spirooxindole-benzimidazole compounds as inhibitors of the signal transducer and activator of p53, a protein involved in regulating cell growth and cancer prevention. The text includes the scientific details of the [3 + 2] cycloaddition (32CA) reaction between azomethine ylide 7a and ethylene 3a within the framework of Molecular Electron Density Theory. The mechanism of the 32CA reaction proceeds through a two-stage one-step process, with emphasis on the highly asynchronous transition state structure. The anti-cancer properties of the synthesized compounds, particularly 6a and 6d, were evaluated. The inhibitory effects of these compounds on the growth of tumor cells (MDA-MB 231 and PC-3) were quantified using IC50 values. This study highlights activation of the p53 pathway by compounds 6a and 6d, leading to upregulation of p53 expression and downregulation of cyclin D and NF-kappa B in treated cells. Additionally, we explored the binding affinity of spirooxindole analogs, particularly compound 6d, to MDM2, a protein involved in regulation of p53. The binding mode and position of compound 6d were compared with those of a co-crystallized standard ligand, suggesting its potential as a lead compound for further preclinical research.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30104 - Pharmacology and pharmacy

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

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

Name of the periodical

Frontiers in Pharmacology

ISSN

1663-9812

e-ISSN

—

Volume of the periodical

15

Issue of the periodical within the volume

April 2024

Country of publishing house

CH - SWITZERLAND

Number of pages

22

Pages from-to

1358089

UT code for WoS article

001206435000001

EID of the result in the Scopus database

2-s2.0-85191052620