Abstract
Decrease of ceramide in the skin is one of the aggravating factors of atopic dermatitis. The skin is often infected by ceramidase-producing bacteria, such as Pseudomonas aeruginosa. The bacterial ceramidase then degrades ceramide in the skin. To develop anti-atopic dermatitis drugs, we searched for ceramidase inhibitors, which led to the discovery of ceramidastin, a novel inhibitor of bacterial ceramidase, from the culture broth of Penicillium sp. Mer-f17067. Ceramidastin inhibited the bacterial ceramidase with an IC(50) value of 6.25 microg ml(-1). Here we describe the isolation, physicochemical properties, structure determination and biological activity of ceramidastin.
MeSH terms
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Animals
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Antibiotics, Antineoplastic / isolation & purification
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Antibiotics, Antineoplastic / pharmacology
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Antibiotics, Antineoplastic / toxicity
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Cell Line, Tumor
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Cell Survival / drug effects
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Ceramidases / antagonists & inhibitors*
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Cyclooctanes / isolation & purification*
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Cyclooctanes / pharmacology*
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Cyclooctanes / toxicity
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Dermatitis, Atopic / drug therapy
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Dermatitis, Atopic / enzymology
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Enzyme Inhibitors / isolation & purification*
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Enzyme Inhibitors / pharmacology*
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Enzyme Inhibitors / toxicity
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Female
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Fermentation
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Humans
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Magnetic Resonance Spectroscopy
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Maleic Anhydrides / isolation & purification*
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Maleic Anhydrides / pharmacology*
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Maleic Anhydrides / toxicity
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Mice
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Mice, Inbred ICR
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Molecular Conformation
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Penicillium / classification
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Penicillium / metabolism*
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Pseudomonas / enzymology
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Spectrometry, Mass, Electrospray Ionization
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Spectrophotometry, Ultraviolet
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Tetrazolium Salts
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Thiazoles
Substances
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Antibiotics, Antineoplastic
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Cyclooctanes
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Enzyme Inhibitors
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Maleic Anhydrides
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Tetrazolium Salts
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Thiazoles
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ceramidastin
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Ceramidases
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thiazolyl blue