0597545 - MBÚ 2025 RIV US eng J - Journal Article
Hurtová, Martina - Brdová, D. - Křížkovská, B. - Tedeschi, G. - Nejedlý, T. - Strnad, O. - Dobiasová, S. - Osifová, Zuzana - KroneislovÁ, G. - Lipov, J. - Valentová, Kateřina - Viktorová, J. - Křen, Vladimír
Nitrogen-Containing Flavonoids-Preparation and Biological Activity.
ACS Omega. Roč. 9, č. 32 (2024), s. 34938-34950. ISSN 2470-1343. E-ISSN 2470-1343
R&D Projects: GA MŠMT(CZ) LUC23061; GA MŠMT(CZ) EH22_008/0004597; GA MŠMT(CZ) LX22NPO5103; GA MŠMT(CZ) LM2023055; GA ČR GA21-00551S
Research Infrastructure: e-INFRA CZ II - 90254
Institutional support: RVO:61388971 ; RVO:61388963
Keywords : multidrug resistance * Staphylococcus aureus * cross-coupling reaction * aryl halides * flavonoids
OECD category: Microbiology; Analytical chemistry (UOCHB-X)
Impact factor: 3.7, year: 2023 ; AIS: 0.637, rok: 2023
Method of publishing: Open access
Result website:
https://pubs.acs.org/doi/10.1021/acsomega.4c04627DOI: https://doi.org/10.1021/acsomega.4c04627

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.
Permanent Link: https://hdl.handle.net/11104/0355479


Research data: pubs.acs.org