2025/03/08 by Artem Tsalyy, Michal Kráľ, Róbert Reiberger +4 · 1 voice
Medicine · Pharmacology, Toxicology and Pharmaceutics · #Bioactive Compounds and Antitumor Agents #Influenza Virus Research Studies #Monoclonal and Polyclonal Antibodies Research
paper · doi:10.1016/j.bmcl.2025.130178
openalex publication_date 2025/03/08 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/23
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 Mg 2+ or Mn 2+ 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 (IC 50 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. • A large set of C-8 arylated luteolin derivatives was synthesized. • Inhibitory potencies (IC 50 values) quantified with AlphaScreen technology. • Some compounds demonstrated nanomolar antiviral activity against influenza. • This study described protection group-free Suzuki couplings on flavonoid scaffold. • Derivative with 3-carboxylphenyl moiety at the C-8 position was the most potent inhibitor.