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 compou...

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Bibliographic Details
Published in:ChemistrySelect (Weinheim) 2019-04, Vol.4 (15), p.4582-4587
Main Authors: Kos, Jiri, Ku, Chuen Fai, Kapustikova, Iva, Oravec, Michal, Zhang, Hong‐Jie, Jampilek, Josef
Format: Article
Language:English
Subjects:
cytotoxicity
H5N1 influenza virus
hydroxyquinolinecarboxanilides
lipophilicity
microwave-assisted synthesis
structure-activity relationships
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Summary: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. A series of thirty‐two ring‐substituted 8‐hydroxyquinoline‐2‐carboxanilides prepared by microwave‐assisted synthesis was screened for the cytotoxicity using A549 cells, and determined nontoxic compounds were then tested for their activity against highly pathogenic H5N1 avian influenza virus. The most effective compounds showed the activity in the range from IC50 = 11.3 to IC50 = 31.2 μM. The inhibitory activity of the compounds depends on the position of halogen substituents and is also affected by the lipophilicity and electron properties.
ISSN:2365-6549
2365-6549
DOI:10.1002/slct.201900873