8-Hydroxyquinoline-2-Carboxanilides as Antiviral Agents Against Avian Influenza Virus

Series of thirty-two mono-, di- and tri-substituted 8-hydroxyquinoline-2-carboxanilides were prepared by microwave-assisted synthesis. The compounds were characterized, and their lipophilicity was experimentally determined. Primary in vitro screening of the cytotoxicity of all the synthesized compounds was performed using adenocarcinomic human alveolar basal epithelial cells (A549), and determined nontoxic compounds were then tested for their activity against highly pathogenic H5N1 avian influenza virus. 8-Hydroxy-N-(3,4,5-trichlorophenyl)quinoline-2-carboxamide, N-(3-chloro-2-fluorophenyl)-8-hydroxyquinoline-2-carboxamide and N-(3,4-dichlorophenyl)-8-hydroxyquinoline-2-carboxamide demonstrated the highest activity within the investigated series (IC ₅₀  = 11.3, 21.2 and 31.2 μM, respectively), while N-(4-chloro-2-fluorophenyl)-8-hydroxyquinoline-2-carboxamide expressed the highest cytotoxic effect (CC ₅₀  = 31.6 μM). In general, the inhibitory activity of the compounds depends on the position of halogen substituents on the anilide ring and is also affected by the lipophilicity and electron properties of individual substituents of the anilide part of the molecule. The structure-activity relationships are discussed.