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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antifungal Agents / pharmacology
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Aspartic Acid Endopeptidases / antagonists & inhibitors*
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Aspartic Acid Endopeptidases / metabolism
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Candida albicans / drug effects*
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Candida albicans / enzymology
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Candida albicans / pathogenicity
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Candidiasis / microbiology
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Candidiasis / prevention & control
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Dose-Response Relationship, Drug
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Drug Resistance, Fungal / drug effects
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Female
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Fluconazole / pharmacology
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Fungal Proteins / antagonists & inhibitors*
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Fungal Proteins / metabolism
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Humans
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Models, Chemical
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Molecular Structure
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Pepstatins / chemistry
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Peptide Library
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Peptides, Cyclic / chemical synthesis
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Peptides, Cyclic / chemistry
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Peptides, Cyclic / pharmacology*
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Rats
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Rats, Wistar
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Structure-Activity Relationship
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Virulence
Substances
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Antifungal Agents
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Enzyme Inhibitors
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Fungal Proteins
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Pepstatins
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Peptide Library
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Peptides, Cyclic
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Fluconazole
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Aspartic Acid Endopeptidases
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SAP2 protein, Candida
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pepstatin