F-12509A, a new sphingosine kinase inhibitor, produced by a discomycete

J Antibiot (Tokyo). 2000 May;53(5):459-66. doi: 10.7164/antibiotics.53.459.

Abstract

In the course of our screening for inhibitors of sphingosine kinase, we found an active compound from a culture broth of a discomycete, Trichopezizella barbata SANK 25395. The structure of the compound, named F-12509A, was elucidated by a combination of spectroscopic analyses, to be a new sesquiterpene quinone consisting of a drimane moiety and a dihydroxybenzoquinone. Enzyme kinetic analyses showed that F-12509A inhibits sphingosine kinase activity in a competitive manner with respect to sphingosine, with a Ki value of 18 microM.

MeSH terms

  • Animals
  • Ascomycota / metabolism*
  • Benzoquinones / chemistry
  • Benzoquinones / metabolism
  • Benzoquinones / pharmacology*
  • Brain / drug effects
  • Brain / enzymology
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Kinetics
  • Liver / drug effects
  • Liver / enzymology
  • Male
  • Microsomes / drug effects
  • Microsomes / enzymology
  • Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors*
  • Rats
  • Rats, Wistar
  • Substrate Specificity

Substances

  • Benzoquinones
  • Enzyme Inhibitors
  • F 12509A
  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase