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 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.
School of Chemistry, Raymond & Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, 6997801, Tel Aviv, Israel.
Raphael I
RI
Benhamou
School of Chemistry, Raymond & Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, 6997801, Tel Aviv, Israel.
Kfir B
KB
Steinbuch
School of Chemistry, Raymond & Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, 6997801, Tel Aviv, Israel. mfridman@post.tau.ac.il.
Micha
M
Fridman
D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology*; D044182:Benzylisoquinolines / Q000737:chemistry*; D002176:Candida albicans / Q000737:chemistry*; D041221:Candida glabrata / Q000737:chemistry*; D002412:Cations / Q000737:chemistry*; D006461:Hemolysis; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests
D000935:Antifungal Agents; D044182:Benzylisoquinolines; D002412:Cations; D007093:Imidazoles; C009438:tetrandrine
aminoglycosides; antifungal agents; cationic amphiphiles; hemolysis; membrane disruptors