Kodaistatins, novel inhibitors of glucose-6-phosphate translocase T1 from Aspergillus terreus thom DSM 11247. Isolation and structural elucidation

J Antibiot (Tokyo). 2000 Jul;53(7):677-86. doi: 10.7164/antibiotics.53.677.

Abstract

Two novel compounds, kodaistatin A, C35H34O11, molecular weight 630, and kodaistatin C, C35H34O12, molecular weight 646, have been isolated from cultures of Aspergillus terreus Thom DSM 11247 by solid-phase extraction, size-exclusion chromatography, and various preparative HPLC steps. The use of a range of 2D NMR measurements, in particular 13C-13C correlation measurements, has led to the clarification of the structure of kodaistatin A. Kodaistatin C is a hydroxylated derivative of kodaistatin A. Both natural products contain hydroxylated aspulvinones and identical highly substituted polyketide units. An X-ray single crystal structure analysis of aspulvinon E demonstrated the z-configuration at the central double bond. The kodaistatins are effective inhibitors of the glucose-6-phosphate translocase component of the glucose-6-phosphatase system (EC 3.1.3.9), an enzyme system which is important for the control of blood glucose levels. The IC50 is 80 nM for kodaistatin A and 130 nM for kodaistatin C.

MeSH terms

  • Animals
  • Antiporters
  • Aspergillus / metabolism*
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / enzymology
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology*
  • Inhibitory Concentration 50
  • Lactones / chemistry
  • Lactones / isolation & purification
  • Lactones / pharmacology
  • Liver / drug effects
  • Liver / enzymology
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology
  • Molecular Structure
  • Monosaccharide Transport Proteins
  • Phosphotransferases / antagonists & inhibitors*
  • Rats

Substances

  • Antiporters
  • Enzyme Inhibitors
  • Lactones
  • Monosaccharide Transport Proteins
  • Slc37a4 protein, rat
  • aspulvinon E
  • glucose 6-phosphate(transporter)
  • kodaistatin A
  • kodaistatin C
  • Phosphotransferases