Structure-aided optimization of 3-O-β-chacotriosyl epiursolic acid derivatives as novel H5N1 virus entry inhibitors.
3-Epiursolic acid saponins
H5N1 entry inhibitors
Semi-synthesis
Structure–activity relationships
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
15 11 2020
15 11 2020
Historique:
received:
15
07
2020
revised:
21
08
2020
accepted:
21
08
2020
pubmed:
4
9
2020
medline:
23
6
2021
entrez:
4
9
2020
Statut:
ppublish
Résumé
It is urgent to develop new antiviral agents due to the continuous emergence of drug-resistant strains of influenza virus. Our earlier studies have identified that certain pentacyclic triterpene saponins with 3-O-β-chacotriosyl residue are novel H5N1 virus entry inhibitors. In the present study, a series of C-28 modified 3-O-β-chacotriosyl epiursolic acid derivatives via conjugation with different kinds of sides were synthesized, of which anti-H5N1 activities in A549 cells were evaluated in vitro. Among them, 10 exhibited strongest anti-H5N1 potency at the low-micromole level without cytotoxicity, surpassing the potency of ribavirin. Further mechanism studies of the lead compound 10 based on HI, SPR and molecular modeling revealed that these new 3-epiursolic acid saponins could bind tightly to the viral envelope HA protein, thus blocking the invasion of H5N1 viruses into host cells.
Identifiants
pubmed: 32882419
pii: S0960-894X(20)30629-6
doi: 10.1016/j.bmcl.2020.127518
pii:
doi:
Substances chimiques
Antiviral Agents
0
Triterpenes
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
127518Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.