Toward a clinical antifungal peptoid: Investigations into the therapeutic potential of AEC5.
Antifungal Agents
/ chemistry
Cell Line
Cryptococcus neoformans
/ drug effects
Drug Synergism
Flucytosine
/ pharmacology
Gram-Negative Bacteria
/ drug effects
Gram-Positive Bacteria
/ drug effects
Half-Life
Humans
Kidney
/ drug effects
Liver
/ drug effects
Macrophages
/ cytology
Meningitis, Cryptococcal
/ drug therapy
Microbial Sensitivity Tests
Peptoids
/ chemistry
Sorbitol
/ chemistry
Cryptococcus neoformans
antifungal
peptoids
Journal
Biopolymers
ISSN: 1097-0282
Titre abrégé: Biopolymers
Pays: United States
ID NLM: 0372525
Informations de publication
Date de publication:
Jun 2019
Jun 2019
Historique:
received:
15
11
2018
revised:
13
03
2019
accepted:
18
03
2019
pubmed:
3
4
2019
medline:
31
12
2019
entrez:
3
4
2019
Statut:
ppublish
Résumé
Cryptococcus neoformans is a fungal pathogen that causes cryptococcal meningitis in immunocompromised individuals. Existing antifungal treatment plans have high mammalian toxicity and increasing drug resistance, demonstrating the dire need for new, nontoxic therapeutics. Antimicrobial peptoids are one alternative to combat this issue. Our lab has recently identified a tripeptoid, AEC5, with promising efficacy and selectivity against C. neoformans. Here, we report studies into the broad-spectrum efficacy, killing kinetics, mechanism of action, in vivo half-life, and subchronic toxicity of this compound. Most notably, these studies have demonstrated that AEC5 rapidly reduces fungal burden, killing all viable fungi within 3 hours. Additionally, AEC5 has an in vivo half-life of 20+ hours and no observable in vivo toxicity following 28 days of daily injections. This research represents an important step in the characterization of AEC5 as a practical treatment option against C. neoformans infections.
Identifiants
pubmed: 30938841
doi: 10.1002/bip.23276
pmc: PMC6660985
mid: NIHMS1021019
doi:
Substances chimiques
AEC5
0
Antifungal Agents
0
Peptoids
0
Sorbitol
506T60A25R
Flucytosine
D83282DT06
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e23276Subventions
Organisme : NIAID NIH HHS
ID : R03 AI112861
Pays : United States
Organisme : National Institute of Allergy and Infectious Diseases
ID : R03AI112861
Organisme : MTSU
Informations de copyright
© 2019 Wiley Periodicals, Inc.
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