Ceramidastin, a novel bacterial ceramidase inhibitor, produced by Penicillium sp. Mer-f17067.
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.
Inoue
Hiroyuki
H
Microbial Chemistry Research Center, Numazu Bio-Medical Research Institute, Numazu-shi, Shizuoka, Japan.
Someno
Tetsuya
T
Kato
Taira
T
Kumagai
Hiroyuki
H
Kawada
Manabu
M
Ikeda
Daishiro
D
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D055572:Ceramidases / Q000037:antagonists & inhibitors*; D034242:Cyclooctanes / Q000302:isolation & purification* / Q000494:pharmacology* / Q000633:toxicity; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D005285:Fermentation; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008299:Maleic Anhydrides / Q000302:isolation & purification* / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D008813:Mice, Inbred ICR; D008968:Molecular Conformation; D010407:Penicillium / Q000145:classification / Q000378:metabolism*; D011549:Pseudomonas / Q000201:enzymology; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D013778:Tetrazolium Salts; D013844:Thiazoles
D000903:Antibiotics, Antineoplastic; D034242:Cyclooctanes; D004791:Enzyme Inhibitors; D008299:Maleic Anhydrides; D013778:Tetrazolium Salts; D013844:Thiazoles; C544381:ceramidastin; D055572:Ceramidases; C022616:thiazolyl blue