Decoding structural determinants of aryl hydrocarbon receptor antagonism by monoterpenoids

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F25%3A00618580" target="_blank" >RIV/68081707:_____/25:00618580 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15310/25:73631569
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0045206825001452?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0045206825001452?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bioorg.2025.108265" target="_blank" >10.1016/j.bioorg.2025.108265</a>

Result language
angličtina
Original language name
Decoding structural determinants of aryl hydrocarbon receptor antagonism by monoterpenoids
Original language description
Monocyclic monoterpenoids carvones have been recently identified as atypical negative allosteric modulators of aryl hydrocarbon receptor (AhR). In the current work, we performed AhR antagonist activity screening of 100 natural and synthetic monoterpenoids, and their analogues. Using SAR approach, structural determinants of AhR antagonist activity were assigned, including C--O presence/position, planarity, and C3/C5-alkylation. Applying pyramidal selection criteria, including absence of residual agonist activity, no cytotoxicity, strong antagonist potency, and pan-antagonism against diverse AhR agonists, we distilled four lead AhR antagonists (carvacrol, ocresol, 3-methyl-S-carvone, EN-2). Whereas 3-methyl-S-carvone and EN-2 were non-competitive AhR panantagonists, carvacrol and o-cresol were ligand-selective AhR antagonists acting by unclear mechanism. We characterized in detail the effects of lead compounds at cellular functions of AhR, including AhR nuclear translocation, AhR dimerization with ARNT, and the expression of AhR-regulated genes. As a proof of concept, effects of monoterpenoids in the murine macrophages were investigated.
Czech name
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Czech description
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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
10608 - Biochemistry and molecular biology

Project
<a href="/en/project/GA23-04662S" target="_blank" >GA23-04662S: Dietary monoterpenoids as a novel class of aryl hydrocarbon receptor negative allosteric modulators in the therapy of colon cancer</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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