8-Hydroxyquinoline-2-carboxanilides as Antiviral Agents against Avian Influenza Virus.

0504172 - ÚVGZ 2020 RIV DE eng J - Journal Article
Kos, J. - Ku, C. F. - Kapustíková, I. - Oravec, Michal - Zhang, H. J. - Jampílek, J.
8-Hydroxyquinoline-2-carboxanilides as Antiviral Agents against Avian Influenza Virus.
ChemistrySelect. Roč. 4, apr (2019), s. 4582-4587, č. článku 15. ISSN 2365-6549. E-ISSN 2365-6549
R&D Projects: GA MŠMT(CZ) EF16_013/0001609; GA MŠMT(CZ) LO1415
Research Infrastructure: CzeCOS II - 90061
Institutional support: RVO:86652079
Keywords : cytoxicity * H5N1 influenza virus * hydroxyquinolinecarboxanilides * lipophilicity * microwave-assisted synthesis * structure-activity relationships
OECD category: Analytical chemistry
Impact factor: 1.811, year: 2019
Method of publishing: Limited access
https://onlinelibrary.wiley.com/doi/abs/10.1002/slct.201900873

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.
Permanent Link: http://hdl.handle.net/11104/0295866