0618038 - ÚOCHB 2026 RIV GB eng J - Článek v odborném periodiku
Tsalyy, Artem - Král, Michal - Reiberger, Róbert - Majer, Pavel - Konvalinka, Jan - Kožíšek, Milan - Machara, Aleš
Design, synthesis, and activity evaluation of C-8 arylated luteolin derivatives as influenza endonuclease inhibitors.
Bioorganic & Medicinal Chemistry. Roč. 121, June (2025), č. článku 130178. ISSN 0968-0896. E-ISSN 1464-3391
Grant CEP: GA MŠMT(CZ) LX22NPO5103
Institucionální podpora: RVO:61388963
Klíčová slova: influenza * endonuclease * flavonoid * inhibitors * RNA polymerase
Impakt faktor: 3.3, rok: 2023 ; AIS: 0.56, rok: 2023
Způsob publikování: Open access
Web výsledku:
https://doi.org/10.1016/j.bmcl.2025.130178DOI: https://doi.org/10.1016/j.bmcl.2025.130178

The polymerase acidic (PA) subunit of the influenza virus, an endonuclease of the RNA-dependent RNA polymerase, represents a viable target for anti-influenza therapies, as evidenced by the efficacy of the FDA-approved drug Xofluza. A characteristic feature of endonuclease inhibitors is their ability to chelate Mg2+ or Mn2+ ions within the enzyme's catalytic site. Previously, our studies identified luteolin and its C-8-glucoside orientin as potent endonuclease inhibitors. This report details our subsequent investigation into the structural modifications of the phenyl moiety attached to the C-8 position of luteolin. The inhibitory potencies (IC50 values) quantified with AlphaScreen technology indicated that substituting the C-8 glucose moiety of orientin resulted in compounds with comparable inhibitory potency. From a series of eighteen compounds, acid 12 with 3-carboxylphenyl moiety at the C-8 position was the most potent inhibitor with nanomolar potency.
Trvalý link: https://hdl.handle.net/11104/0364870