Design, synthesis and structure-activity relationships of 4-phenyl-1H-1,2,3-triazole phenylalanine derivatives as novel HIV-1 capsid inhibitors with promising antiviral activities.
Anti-HIV Agents
/ chemical synthesis
Capsid Proteins
/ antagonists & inhibitors
Cell Line, Tumor
Drug Design
HIV-1
/ chemistry
Humans
Microbial Sensitivity Tests
Microsomes, Liver
/ metabolism
Molecular Dynamics Simulation
Molecular Structure
Phenylalanine
/ analogs & derivatives
Protein Binding
Structure-Activity Relationship
Triazoles
/ chemical synthesis
Virus Replication
/ drug effects
1,2,3-Triazole
CA protein
HIV-1
MD simulation
Phenylalanine derivatives
SPR assay
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
15 Mar 2020
15 Mar 2020
Historique:
received:
22
10
2019
revised:
18
12
2019
accepted:
20
01
2020
pubmed:
18
2
2020
medline:
15
12
2020
entrez:
18
2
2020
Statut:
ppublish
Résumé
HIV-1 CA is involved in different stages of the viral replication cycle, performing essential roles in both early (uncoating, reverse transcription, nuclear import, integration) and late events (assembly). Recent efforts have demonstrated HIV-1 CA protein as a prospective therapeutic target for the development of new antivirals. The most extensively studied CA inhibitor, PF-3450074 (PF-74, discovered by Pfizer), that targets an inter-protomer pocket within the CA hexamer. Herein we reported the design, synthesis, and biological evaluation of a series of 4-phenyl-1H-1,2,3-triazole phenylalanine derivatives as HIV-1 CA inhibitors based on PF-74 scaffold. Most of the analogues demonstrated potent antiviral activities, among them, the anti-HIV-1 activity of 6a-9 (EC
Identifiants
pubmed: 32066010
pii: S0223-5234(20)30052-0
doi: 10.1016/j.ejmech.2020.112085
pmc: PMC7053825
mid: NIHMS1561687
pii:
doi:
Substances chimiques
Anti-HIV Agents
0
Capsid Proteins
0
Triazoles
0
Phenylalanine
47E5O17Y3R
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
112085Subventions
Organisme : NIAID NIH HHS
ID : R01 AI150491
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM125396
Pays : United States
Organisme : NIMH NIH HHS
ID : T32 MH079785
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Masson SAS. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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