A Novel Series of Indole Alkaloid Derivatives Inhibit Dengue and Zika Virus Infection by Interference with the Viral Replication Complex.
NS4B protein
SAR studies
Zika virus
cross resistance
dengue virus
indole alkaloids
mechanisms of action
Journal
Antimicrobial agents and chemotherapy
ISSN: 1098-6596
Titre abrégé: Antimicrob Agents Chemother
Pays: United States
ID NLM: 0315061
Informations de publication
Date de publication:
16 07 2021
16 07 2021
Historique:
pubmed:
19
5
2021
medline:
10
8
2021
entrez:
18
5
2021
Statut:
ppublish
Résumé
Here, we identified a novel class of compounds which demonstrated good antiviral activity against dengue and Zika virus infection. These derivatives constitute intermediates in the synthesis of indole (ervatamine-silicine) alkaloids and share a tetracyclic structure, with an indole and a piperidine fused to a seven-membered carbocyclic ring. Structure-activity relationship studies indicated the importance of substituent at position C-6 and especially the presence of a benzyl ester for the activity and cytotoxicity of the molecules. In addition, the stereochemistry at C-7 and C-8, as well as the presence of an oxazolidine ring, influenced the potency of the compounds. Mechanism of action studies with two analogues of this family (compounds 22 and
Identifiants
pubmed: 34001508
pii: AAC.02349-20
doi: 10.1128/AAC.02349-20
pmc: PMC8284442
doi:
Substances chimiques
Indole Alkaloids
0
Viral Nonstructural Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0234920Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206298/Z/17/Z
Pays : United Kingdom
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