Nitrogen-Containing Flavonoids-Preparation and Biological Activity

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F24%3A00597545" target="_blank" >RIV/61388971:_____/24:00597545 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388963:_____/24:00597545 RIV/60461373:22330/24:43929593 RIV/00064165:_____/24:10483350

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acsomega.4c04627" target="_blank" >https://pubs.acs.org/doi/10.1021/acsomega.4c04627</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acsomega.4c04627" target="_blank" >10.1021/acsomega.4c04627</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Nitrogen-Containing Flavonoids-Preparation and Biological Activity

Popis výsledku v původním jazyce

In this work, we report the application of Buchwald-Hartwig amination for the preparation of new derivatives of quercetin and luteolin. Our investigation delves into the impact of aniline moiety on antioxidant, and anti-inflammatory activity, cytotoxicity, and the ability of flavonoids to modulate drug-resistance mechanisms in bacteria. The anti-inflammatory activity disappeared after the introduction of aniline into the flavonoids and the cytotoxicity remained low. Although the ability of quercetin and luteolin to modulate bacterial resistance to antibiotics has already been published, this is the first report on the molecular mechanism of this process. Both flavonoids attenuate erythromycin resistance by suppressing the ribosomal methyltransferase encoded by the ermA gene in Staphylococcus aureus. Notably, 4-(trifluoromethyl)anilino quercetin emerged as a potent ErmA inhibitor, likely by interacting with the RNA-binding pocket of ErmA. Additionally, both 4-fluoroanilino derivatives effectively impended the staphylococcal efflux system. All the prepared derivatives exhibited superior activity in modulating gentamicin resistance in S. aureus compared to the parent compounds. Overall, the incorporation of substituted anilines into the flavonoid core significantly enhanced its ability to combat multidrug resistance in bacteria.

Název v anglickém jazyce

Nitrogen-Containing Flavonoids-Preparation and Biological Activity

Popis výsledku anglicky

In this work, we report the application of Buchwald-Hartwig amination for the preparation of new derivatives of quercetin and luteolin. Our investigation delves into the impact of aniline moiety on antioxidant, and anti-inflammatory activity, cytotoxicity, and the ability of flavonoids to modulate drug-resistance mechanisms in bacteria. The anti-inflammatory activity disappeared after the introduction of aniline into the flavonoids and the cytotoxicity remained low. Although the ability of quercetin and luteolin to modulate bacterial resistance to antibiotics has already been published, this is the first report on the molecular mechanism of this process. Both flavonoids attenuate erythromycin resistance by suppressing the ribosomal methyltransferase encoded by the ermA gene in Staphylococcus aureus. Notably, 4-(trifluoromethyl)anilino quercetin emerged as a potent ErmA inhibitor, likely by interacting with the RNA-binding pocket of ErmA. Additionally, both 4-fluoroanilino derivatives effectively impended the staphylococcal efflux system. All the prepared derivatives exhibited superior activity in modulating gentamicin resistance in S. aureus compared to the parent compounds. Overall, the incorporation of substituted anilines into the flavonoid core significantly enhanced its ability to combat multidrug resistance in bacteria.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10606 - Microbiology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

ACS Omega

ISSN

2470-1343

e-ISSN

2470-1343

Svazek periodika

9

Číslo periodika v rámci svazku

32

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

34938-34950

Kód UT WoS článku

001280428900001

EID výsledku v databázi Scopus

2-s2.0-85201226441