Attachment of a 5-nitrofuroyl moiety to spirocyclic piperidines produces non-toxic nitrofurans that are efficacious in vitro against multidrug-resistant Mycobacterium tuberculosis.
ARPE-19 cell line
Acylation
Antimycobacterial
ESKAPE panel
Multidrug resistance
Nitrofuran antimicrobials
Non-specific toxicity
Periphery optimization
Prins reaction
Spirocycles
Tuberculosis
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 2019
15 Mar 2019
Historique:
received:
19
07
2018
revised:
17
01
2019
accepted:
17
01
2019
pubmed:
1
2
2019
medline:
6
3
2019
entrez:
1
2
2019
Statut:
ppublish
Résumé
A selectively antimycobacterial compound belonging to the nitrofuran class of antimicrobials has been developed via conjugation of the nitrofuran moiety to a series of spirocyclic piperidines through an amide linkage. It proved to have comparable activity against drug-sensitive (H37Rv) strain as well as multidrug-resistant, patient-derived strains of Mycobacterium tuberculosis. The compound is druglike, showed no appreciable cytotoxicity toward human retinal pigment epithelial cell line ARPE-19 in concentrations up to 100 μM and displayed low toxicity when evaluated in mice.
Identifiants
pubmed: 30703656
pii: S0223-5234(19)30054-6
doi: 10.1016/j.ejmech.2019.01.050
pii:
doi:
Substances chimiques
Antitubercular Agents
0
Nitrofurans
0
Piperidines
0
Spiro Compounds
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
125-135Informations de copyright
Copyright © 2019 Elsevier Masson SAS. All rights reserved.