Abstract
Highly potent 1,3-beta-D-glucan synthase inhibitors, 7b, 10a, 10b and 12, have been identified by the chemical modification of the ornithine residue of a fungicidal macrocyclic lipopeptidolactone, RO-09-3655 (1), isolated from the cultured broth of Deuteromycotinia spp. These compounds showed stronger antifungal activity against systemic candidiasis as well as pulmonary aspergillosis in mice, and less hepatotoxicity as compared with 1.
MeSH terms
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Animals
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Antifungal Agents / chemical synthesis*
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Antifungal Agents / pharmacology
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Antifungal Agents / toxicity
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Aspergillosis, Allergic Bronchopulmonary / complications
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Aspergillosis, Allergic Bronchopulmonary / drug therapy
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Aspergillus fumigatus / drug effects
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Candida / drug effects
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Candidiasis / complications
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Candidiasis / drug therapy
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology
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Enzyme Inhibitors / toxicity
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Glucosyltransferases / antagonists & inhibitors*
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Immunocompromised Host / drug effects
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Inclusion Bodies / drug effects
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Injections, Intravenous
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Membrane Proteins*
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Mice
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Microbial Sensitivity Tests
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Mitosporic Fungi / chemistry
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Peptides, Cyclic / chemical synthesis*
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Peptides, Cyclic / pharmacology
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Peptides, Cyclic / toxicity
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Schizosaccharomyces pombe Proteins*
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Time Factors
Substances
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Antifungal Agents
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Enzyme Inhibitors
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Membrane Proteins
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Peptides, Cyclic
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Schizosaccharomyces pombe Proteins
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lipopeptidolactone
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Glucosyltransferases
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1,3-beta-glucan synthase