title: Short Cationic Antimicrobial Peptides Display Superior Antifungal Activities toward Candidiasis and Onychomycosis in Comparison with Terbinafine and Amorolfine.
abstract: Novel antifungals are in high demand due to the challenges associated with resistant, persistent, and systemic fungal infections. Synthetic mimics of antimicrobial peptides are emerging as a promising class of compounds for antifungal treatment. In the current study, five synthetic cationic antimicrobial tripeptides were evaluated as antifungal therapeutics against 24 pathogenic strains of fungi. Three of the peptides displayed strong general antifungal properties at low micromolar inhibitory concentrations. The most promising peptide, compound 5, was selected and evaluated as an antifungal remedy for Candida albicans candidiasis in a human skin model and for the treatment of Trichophyton rubrum induced onychomycosis in an infected human nail model. Compound 5 was shown to display antifungal properties and a rapid mode of action superior to those of both the commercial comparators Loceryl and Lamisil. Compound 5 was also active against a clinical isolate of Candida albicans with acquired fluconazole resistance.
authors: Department of Chemistry, UiT The Arctic University of Norway , Tromsø, Norway.|Lytix Biopharma AS , Tromsø, Norway.
authors: Wenche
authors: W
authors: Stensen
authors: MedPharm Ltd , Guildford, U.K.
authors: Rob
authors: R
authors: Turner
authors: MedPharm Ltd , Guildford, U.K.|TDDT, University of Hertfordshire , Hatfield, Hertfordshire, U.K.
authors: Marc
authors: M
authors: Brown
authors: Department of Clinical Microbiology, Sahlgrenska University Hospital , Gothenburg, Sweden.
authors: Nahid
authors: N
authors: Kondori
authors: Department of Chemistry, UiT The Arctic University of Norway , Tromsø, Norway.|Lytix Biopharma AS , Tromsø, Norway.
authors: John Sigurd
authors: JS
authors: Svendsen
authors: Department of Chemistry, Materials and Surfaces, SP Technical Research Institute of Sweden , Borås, Sweden.
authors: Johan
authors: J
authors: Svenson
mesh_terms: D000935:Antifungal Agents / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D002176:Candida albicans / Q000187:drug effects / Q000472:pathogenicity; D002177:Candidiasis / Q000188:drug therapy*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009025:Morpholines / Q000627:therapeutic use*; D009281:Naphthalenes / Q000627:therapeutic use*; D014009:Onychomycosis / Q000188:drug therapy*; D012871:Skin Diseases / Q000188:drug therapy / Q000382:microbiology; D000077291:Terbinafine
chemical_list: D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D009025:Morpholines; D009281:Naphthalenes; C038974:amorolfine; D000077291:Terbinafine
keywords: amorolfine; antifungal; antimicrobial peptides; candidiasis; onychomycosis; terbinafine