Antifungal Imidazole-Decorated Cationic Amphiphiles with Markedly Low Hemolytic Activity

Herein we report that an imidazole‐decorated cationic amphiphile derived from the pseudo‐disaccharide nebramine has potent antifungal activity against strains of Candida glabrata pathogens. In combination with the natural bis‐benzylisoquinoline alkaloid tetrandrine the reported antifungal cationic a...

Full description

Saved in:
Bibliographic Details
Published in:Chemistry : a European journal 2016-08, Vol.22 (32), p.11148-11151
Main Authors: Benhamou, Raphael I., Steinbuch, Kfir B., Fridman, Micha
Format: Article
Language:English
Subjects:
aminoglycosides
Antifungal activity
Antifungal agents
Antifungal Agents - chemistry
Antifungal Agents - pharmacology
Benzylisoquinolines - chemistry
Candida
Candida albicans
Candida albicans - chemistry
Candida glabrata
Candida glabrata - chemistry
Cationic
cationic amphiphiles
Cations
Cations - chemistry
Decoration
Disruption
Drug development
Drugs
Efflux
Fungicides
Hemolysis
Humans
Imidazole
Imidazoles - chemistry
Imidazoles - pharmacology
Mammals
membrane disruptors
Microbial Sensitivity Tests
Pathogens
Pumps
Tetrandrine
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Herein we report that an imidazole‐decorated cationic amphiphile derived from the pseudo‐disaccharide nebramine has potent antifungal activity against strains of Candida glabrata pathogens. In combination with the natural bis‐benzylisoquinoline alkaloid tetrandrine the reported antifungal cationic amphiphile demonstrated synergistic antifungal activity against Candida albicans pathogens. This unique membrane disruptor caused no detectible mammalian red blood cell hemolysis at concentrations up to more than two orders of magnitude greater than its minimal inhibitory concentrations against the tested C. glabrata strains. We provide evidence that potency against C. glabrata may be associated with differences between the drug efflux pumps of C. albicans and C. glabrata. Imidazole decorated‐cationic amphiphiles show promise for the development of less toxic membrane‐disrupting antifungal drugs and drug combinations. Antifungal agents: Antifungal aminoglycoside‐derived cationic amphiphiles cause markedly low hemolysis (see graphic) as shown by an imidazole‐decorated cationic amphiphile derived from the pseudo‐disaccharide nebramine, which has potent antifungal activity against strains of Candida glabrata pathogens.
ISSN:0947-6539
1521-3765
DOI:10.1002/chem.201602198