Abstract
Highly potent 1,3-beta-D-glucan synthase inhibitors 10, 11 and 13 have been identified by the chemical modification of the fungicidal macrocyclic lipopeptidolactone, RO-09-3655 (1), isolated from the cultured broth of Deuteromycotinia spp. D-Ornithine derivative (10) showed improved antifungal activity in the systemic candidiasis model in mice and reduced hepatotoxicity in vitro, as compared with 1.
MeSH terms
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Animals
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Anti-Bacterial Agents / chemical synthesis
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology
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Antifungal Agents / chemical synthesis*
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Antifungal Agents / chemistry
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Antifungal Agents / pharmacology*
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Candida albicans / drug effects
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Candidiasis / complications
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Candidiasis / drug therapy
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Combinatorial Chemistry Techniques
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Disease Models, Animal
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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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Glucosyltransferases / antagonists & inhibitors*
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Inclusion Bodies / drug effects
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Inclusion Bodies / microbiology
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Inhibitory Concentration 50
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Lactones / chemical synthesis
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Lactones / chemistry
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Lactones / pharmacology
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Liver / drug effects
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Liver / microbiology
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Liver / pathology
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Membrane Proteins*
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Mice
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Microbial Sensitivity Tests
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Peptides
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Schizosaccharomyces pombe Proteins*
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Structure-Activity Relationship
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Survival Rate
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Therapeutic Equivalency
Substances
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Anti-Bacterial Agents
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Antifungal Agents
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Enzyme Inhibitors
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Lactones
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Membrane Proteins
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Peptides
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Schizosaccharomyces pombe Proteins
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Glucosyltransferases
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1,3-beta-glucan synthase