Methylcarvones as immunomodulators through antagonism of aryl hydrocarbon receptor

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00098892%3A_____%2F25%3A10159555" target="_blank" >RIV/00098892:_____/25:10159555 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0045206825011368?pes=vor&utm_source=scopus&getft_integrator=scopus" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0045206825011368?pes=vor&utm_source=scopus&getft_integrator=scopus</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bioorg.2025.109256" target="_blank" >10.1016/j.bioorg.2025.109256</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Methylcarvones as immunomodulators through antagonism of aryl hydrocarbon receptor

Popis výsledku v původním jazyce

Monocyclic monoterpenoids have been demonstrated as atypical negative allosteric modulators of aryl hydrocarbon receptor AhR. The alkylation of the skeleton has been identified as a factor modulating the AhR antagonist activity of S-carvone. In the present study, we synthesized methylated derivatives of S-carvone, and a complex series of experimental approaches has been employed to characterize the interactions of novel compounds with AhR. Molecular docking to AhR carvone-binding site revealed binding energies for 6-methylated carvones superior to that of S-carvone. This prediction was corroborated by microscale thermophoresis, where 6-methylated carvones displayed stronger binding to AhR N-terminal region, as compared to S-carvone. Methylated carvones inhibited AhR transcriptional activity in vitro in cell lines, as revealed by reporter gene assay and RT-PCR. However, their effects were weaker than those predicted by molecular docking, which might be due to the transmembrane transport and metabolism. As a proof-of-concept, we show immunomodulatory effects of S-carvone and its methyl derivatives in the model of differentiated THP1 macrophages polarized into M1/M2 phenotypes.

Název v anglickém jazyce

Methylcarvones as immunomodulators through antagonism of aryl hydrocarbon receptor

Popis výsledku anglicky

Monocyclic monoterpenoids have been demonstrated as atypical negative allosteric modulators of aryl hydrocarbon receptor AhR. The alkylation of the skeleton has been identified as a factor modulating the AhR antagonist activity of S-carvone. In the present study, we synthesized methylated derivatives of S-carvone, and a complex series of experimental approaches has been employed to characterize the interactions of novel compounds with AhR. Molecular docking to AhR carvone-binding site revealed binding energies for 6-methylated carvones superior to that of S-carvone. This prediction was corroborated by microscale thermophoresis, where 6-methylated carvones displayed stronger binding to AhR N-terminal region, as compared to S-carvone. Methylated carvones inhibited AhR transcriptional activity in vitro in cell lines, as revealed by reporter gene assay and RT-PCR. However, their effects were weaker than those predicted by molecular docking, which might be due to the transmembrane transport and metabolism. As a proof-of-concept, we show immunomodulatory effects of S-carvone and its methyl derivatives in the model of differentiated THP1 macrophages polarized into M1/M2 phenotypes.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30107 - Medicinal chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Bioorganic Chemistry

ISSN

0045-2068

e-ISSN

1090-2120

Svazek periodika

167

Číslo periodika v rámci svazku

December

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

109256

Kód UT WoS článku

001621991500001

EID výsledku v databázi Scopus

2-s2.0-105021927219