Regio- and Stereoselective Synthesis of Nitro-fatty Acids as NRF2 Pathway Activators Working under Ambient or Hypoxic Conditions

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F25%3A00637220" target="_blank" >RIV/61389030:_____/25:00637220 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68081707:_____/25:00637220 RIV/61989592:15310/25:73632042 RIV/61989592:15110/25:73632042

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acs.jmedchem.5c00982" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jmedchem.5c00982</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jmedchem.5c00982" target="_blank" >10.1021/acs.jmedchem.5c00982</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Regio- and Stereoselective Synthesis of Nitro-fatty Acids as NRF2 Pathway Activators Working under Ambient or Hypoxic Conditions

Popis výsledku v původním jazyce

Nitro-fatty acids (NO2FAs) are endogenously produced electrophiles and NRF2 activators with therapeutic potential. We developed a synthetic protocol combining a Henry reaction and base-promoted beta-elimination, yielding ultrapure regio/stereoisomers of nitro-stearic (NO2SA), nitro-oleic (NO2OA), and conjugated/bis-allylic nitro-linoleic (NO2LA) acids. These were tested for NRF2 pathway activation in bone marrow cells under different oxygen conditions. We observed that 9- and 10-NO 2 OA, and 10-NO 2 LA increased NRF2 stabilization under hypoxia, while 9- and 10-NO 2 OA significantly upregulated Hmox1 and Gclm at all oxygen levels. 9- and 10-NO 2 OA enhanced HO-1 and GCLM proteins independently of oxygen, while 10-NO 2 LA was oxygen-dependent, boosting HO-1 under hypoxia and GCLM under ambient conditions. Moreover, 10-NO 2 OA and 10-NO 2 LA induced NRF2 nuclear translocation. In contrast, the saturated 10-NO 2 SA, which has lower electron-acceptor ability, was inactive. In summary, these findings suggest the biological activity of NO2FAs is dependent on oxygen level, which could be used in future research of other oxidative stress-dependent pathways.

Název v anglickém jazyce

Regio- and Stereoselective Synthesis of Nitro-fatty Acids as NRF2 Pathway Activators Working under Ambient or Hypoxic Conditions

Popis výsledku anglicky

Nitro-fatty acids (NO2FAs) are endogenously produced electrophiles and NRF2 activators with therapeutic potential. We developed a synthetic protocol combining a Henry reaction and base-promoted beta-elimination, yielding ultrapure regio/stereoisomers of nitro-stearic (NO2SA), nitro-oleic (NO2OA), and conjugated/bis-allylic nitro-linoleic (NO2LA) acids. These were tested for NRF2 pathway activation in bone marrow cells under different oxygen conditions. We observed that 9- and 10-NO 2 OA, and 10-NO 2 LA increased NRF2 stabilization under hypoxia, while 9- and 10-NO 2 OA significantly upregulated Hmox1 and Gclm at all oxygen levels. 9- and 10-NO 2 OA enhanced HO-1 and GCLM proteins independently of oxygen, while 10-NO 2 LA was oxygen-dependent, boosting HO-1 under hypoxia and GCLM under ambient conditions. Moreover, 10-NO 2 OA and 10-NO 2 LA induced NRF2 nuclear translocation. In contrast, the saturated 10-NO 2 SA, which has lower electron-acceptor ability, was inactive. In summary, these findings suggest the biological activity of NO2FAs is dependent on oxygen level, which could be used in future research of other oxidative stress-dependent pathways.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10611 - Plant sciences, botany

Projekt

<a href="/cs/project/GA23-06051S" target="_blank" >GA23-06051S: Elektrofilní nitrované mastné kyseliny jako ochrana proti poškození krvetvorby způsobené ionizujícím zářením: ovlivnění dráhy NRF2</a><br>

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

Journal of Medicinal Chemistry

ISSN

0022-2623

e-ISSN

1520-4804

Svazek periodika

68

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

12172-12184

Kód UT WoS článku

001497562200001

EID výsledku v databázi Scopus

2-s2.0-105006678085