Abstract
A new series of acid-stable antifungal agents having strong inhibitory activity against Candida albicans N-myristoyltransferase (CaNmt) has been developed starting from acid-unstable benzofuranylmethyl aryl ether 2. The inhibitor design is based on X-ray crystallographic analysis of a CaNmt complex with aryl ether 3. Among the new inhibitors, pyridine derivative 8b and benzimidazole derivative 8k showed clear antifungal activity in a murine systemic candidiasis model.
MeSH terms
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Acyltransferases / antagonists & inhibitors*
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Animals
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Antifungal Agents / chemical synthesis*
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Antifungal Agents / pharmacokinetics
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Antifungal Agents / pharmacology
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Benzofurans / chemical synthesis*
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Benzofurans / pharmacokinetics
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Benzofurans / pharmacology
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Candida albicans / drug effects
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Candida albicans / enzymology
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Disease Models, Animal
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Drug Design
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Drug Stability
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacokinetics
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Enzyme Inhibitors / pharmacology
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Fungal Proteins / antagonists & inhibitors*
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Inhibitory Concentration 50
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Mice
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Models, Molecular
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Structure-Activity Relationship
Substances
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Antifungal Agents
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Benzofurans
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Enzyme Inhibitors
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Fungal Proteins
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Acyltransferases
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glycylpeptide N-tetradecanoyltransferase