Anti-influenza A virus activity and structure-activity relationship of a series of nitrobenzoxadiazole derivatives.
J Enzyme Inhib Med Chem
; 36(1): 2128-2138, 2021 Dec.
Article
em En
| MEDLINE
| ID: mdl-34583607
ABSTRACT
Influenza viruses represent a major threat to human health and are responsible for seasonal epidemics, along with pandemics. Currently, few therapeutic options are available, with most drugs being at risk of the insurgence of resistant strains. Hence, novel approaches targeting less explored pathways are urgently needed. In this work, we assayed a library of nitrobenzoxadiazole derivatives against the influenza virus A/Puerto Rico/8/34 H1N1 (PR8) strain. We identified three promising 4-thioether substituted nitrobenzoxadiazoles (12, 17, and 25) that were able to inhibit viral replication at low micromolar concentrations in two different infected cell lines using a haemagglutination assay. We further assessed these molecules using an In-Cell Western assay, which confirmed their potency in the low micromolar range. Among the three molecules, 12 and 25 displayed the most favourable profile of activity and selectivity and were selected as hit compounds for future optimisation studies.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Vírus da Influenza A Subtipo H1N1
/
4-Cloro-7-nitrobenzofurazano
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Enzyme Inhib Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Itália