Modulation of aryl hydrocarbon receptor activity by halogenated indoles
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F24%3A73626896" target="_blank" >RIV/61989592:15310/24:73626896 - isvavai.cz</a>
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S096808962400378X" target="_blank" >https://www.sciencedirect.com/science/article/pii/S096808962400378X</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bmc.2024.117964" target="_blank" >10.1016/j.bmc.2024.117964</a>
Alternative languages
Result language
angličtina
Original language name
Modulation of aryl hydrocarbon receptor activity by halogenated indoles
Original language description
The aryl hydrocarbon receptor (AhR) is a cytosolic ligand-activated transcription factor integral to various physiological and pathological processes. Among its diverse ligands, indole-based compounds have garnered attention due to their significant biological activity and potential therapeutic applications. This study explores the activation of AhR by structurally diverse halogenated indoles. We evaluated the transcriptional activity of AhR and cell viability in the human LS174T-AhR-luc reporter cell line. Among the tested compounds, 4-FI, 7-FI, 6-BrI, 7-BrI, 6-Cl-2-ox, 5-Br-2-ox, and 6-Br-2-ox activated AhR in a concentration-dependent manner, displaying high efficacy and potency. Molecular docking analysis revealed moderate binding affinities of these compounds to the PAS-B domain of AhR, corroborated by competitive radioligand binding assays. Functional assays showed that halogenated indoles induce the formation of AhR-ARNT heterodimer and enhance the binding of the AhR to the CYP1A1 promoter. Additionally, 4-FI and 7-FI exhibited anti-inflammatory properties in Caco-2 cell models, highlighting their potential for therapeutic applications. This study underscores the significance of the type and position of halogen moiety in indole scaffold, suggesting their potential as candidates for developing therapeutics drugs to treat conditions such as inflammatory bowel disease via AhR activation.
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
30104 - Pharmacology and pharmacy
Result continuities
Project
<a href="/en/project/GA22-00355S" target="_blank" >GA22-00355S: Pharmacological mimicry of microbial metabolites in the modulation of intestinal health</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
Bioorganic and Medicinal Chemistry
ISSN
0968-0896
e-ISSN
1464-3391
Volume of the periodical
114
Issue of the periodical within the volume
NOV
Country of publishing house
GB - UNITED KINGDOM
Number of pages
12
Pages from-to
"117964-1"-"117964-12"
UT code for WoS article
001344424900001
EID of the result in the Scopus database
2-s2.0-85207006661