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

Abstract

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 (IC50 = 11.3, 21.2 and 31.2 μM, respectively), while N‐(4‐chloro‐2‐fluorophenyl)‐8‐hydroxyquinoline‐2‐carboxamide expressed the highest cytotoxic effect (CC50 = 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.

Study of ADMET Descriptors of Novel Chlorinated N-Arylcinnamamides

“…The only difference between all experimental and predicted values was observed for compounds 5 (R = 2,4-Cl) and 6 (R = 2,5-Cl), where compound 5 actually shows a higher lipophilicity than compound 6, which was predicted by the software vice versa: log P = 5.68 (5) and log P = 5.72 (6). This is caused by specific intra-and intermolecular interactions of the substituent in the ortho position with other spatially close moieties/fragments and the polar medium as was described recently [15,18,[19][20][21][22]. Nevertheless, based on the results of this preliminary short study of several selected new anilides of 3,4dichlorocinnamic acid, it can be assumed that the log P values predicted by ACD/Percepta recognized hydro-lipophilic properties in a good agreement with experimentally determined values, and thus, this software can be used for these simple chlorinated derivatives as a useful and mainly fast tool for the subsequent investigation of structure-activity relationships.…”

Recent Advances in the Synthesis and Biological Activity of 8-Hydroxyquinolines

“…In a similar fashion, Kos and coworkers reported the microwave-assisted synthesis of thirty-two mono-, di-, and tri-substituted 8-hydroxyquinoline-2-carboxanilides, as shown in Scheme 2 [ 8 ]. Condensation of activated 8-hydroxyquinoline-2-carboxylic acid ( 5 ) with substituted aniline 6 in the presence of by phosphorus trichloride yielded the desired target compound 7 in good amounts (61–79%).…”

Development of an efficient, one‐pot, multicomponent protocol for synthesis of 8‐hydroxy‐4‐phenyl‐1,2‐dihydroquinoline derivatives

“…[ 1–18 ] Quinoline derivatives are heterocyclic compounds that are used as selective and potent drugs against many diseases. They show excellent antiviral activity against dengue Zika and avian influenza virus [ 19–21 ] and now in current year even against COVID‐19. [ 22–24 ] Modification of quinoline moiety through substitution can improve its physical and chemical properties and also pharmacological behavior.…”