Design, synthesis of oleanolic acid-saccharide conjugates using click chemistry methodology and study of their anti-influenza activity.
Eur J Med Chem
; 182: 111622, 2019 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-31425909
ABSTRACT
The development of entry inhibitors is an emerging approach to the inhibition of influenza virus. In our previous research, oleanolic acid (OA) was discovered as a mild influenza hemagglutinin (HA) inhibitor. Herein, as a further study, we report the preparation of a series of OA-saccharide conjugates via the CuAAC reaction, and the anti-influenza activity of these compounds was evaluated in vitro. Among them, compound 11b, an OA-glucose conjugate, showed a significantly increased anti-influenza activity with an IC50 of 5.47⯵M, and no obvious cytotoxic effect on MDCK cells was observed at 100⯵M. Hemagglutination inhibition assay and docking experiment indicated that 11b might interfere with influenza virus infection by acting on HA protein. Broad-spectrum anti-influenza experiments showed 11b to be robustly potent against 5 different strains, including influenza A and B viruses, with IC50 values at the low-micromole level. Overall, this finding further extends the utility of OA-saccharide conjugates in anti-influenza virus drug design.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Oleanólico
/
Antivirais
/
Oligossacarídeos
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Vírus da Influenza A
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Desenho de Fármacos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China