S-15183a and b, new sphingosine kinase inhibitors, produced by a fungus.
In the course of our screening for inhibitors of sphingosine kinase, we found two active compounds in a culture broth of a fungus, Zopfiella inermis SANK 15183. The structures of the compounds, named S-15183a and b, were elucidated by a combination of spectroscopic analyses to be new azaphilone-type metabolites. S-15183a and b inhibited sphingosine kinase from rat liver with IC50 values of 2.5 and 1.6 microM, respectively. S-15183a also inhibited endogenous SPH kinase activity in intact platelets.
Kono
K
K
Pharmacology and Molecular Biology Research Laboratories, Research Institute, Sankyo Co, Ltd, Shinagawa, Tokyo, Japan.
Tanaka
M
M
Ono
Y
Y
Hosoya
T
T
Ogita
T
T
Kohama
T
T
D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D002474:Cell-Free System; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D005285:Fermentation; D006801:Humans; D006865:Hydrogenation; D009682:Magnetic Resonance Spectroscopy; D003904:Mitosporic Fungi / Q000737:chemistry* / Q000254:growth & development / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013110:Sphingosine / Q000031:analogs & derivatives / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D013379:Substrate Specificity; D000099157:Sphingosine Kinase
D004791:Enzyme Inhibitors; D017853:Phosphotransferases (Alcohol Group Acceptor); D013110:Sphingosine; D000099157:Sphingosine Kinase; C433004:S-15183a; C433005:S-15183b