title: Identification of inhibitors of drug-resistant Candida albicans strains from a library of bicyclic peptidomimetic compounds.
abstract: The screening of a library of small molecule peptidomimetics toward secreted aspartic proteinase-2 (SAP2) of Candida albicans allowed us to identify two compounds that showed in vitro inhibitory potency comparable to pepstatin A. In an experimental model of vaginal candidiasis, the two candidate compounds were as active as a therapeutic dose of fluconazole. Importantly, this activity was fully preserved when the challenger was a fluconazole-resistant strain of the fungus. Altogether, our data demonstrate SAP2 as a valid C. albicans target for the development of new drugs against this important human pathogen.
authors.affiliation: Department of Chemistry Ugo Schiff, University of Florence, Polo Scientifico e Tecnologico, Via della Lastruccia 13, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Trabocchi
authors.forename: Claudia
authors.initials: C
authors.lastname: Mannino
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Machetti
authors.forename: Flavia
authors.initials: F
authors.lastname: De Bernardis
authors.forename: Silvia
authors.initials: S
authors.lastname: Arancia
authors.forename: Roberto
authors.initials: R
authors.lastname: Cauda
authors.forename: Antonio
authors.initials: A
authors.lastname: Cassone
authors.forename: Antonio
authors.initials: A
authors.lastname: Guarna
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002176:Candida albicans / Q000187:drug effects* / Q000201:enzymology / Q000472:pathogenicity; D002177:Candidiasis / Q000382:microbiology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D025141:Drug Resistance, Fungal / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D015725:Fluconazole / Q000494:pharmacology; D005656:Fungal Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008956:Models, Chemical; D015394:Molecular Structure; D010436:Pepstatins / Q000737:chemistry; D019151:Peptide Library; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014774:Virulence
chemical_list: D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D010436:Pepstatins; D019151:Peptide Library; D010456:Peptides, Cyclic; D015725:Fluconazole; D016282:Aspartic Acid Endopeptidases; C090753:SAP2 protein, Candida; C031375:pepstatin