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Inhibition of TNF-alpha promoter activity and synthesis by A11-99-1, a new cyclopentenone from the ascomycete Mollisia melaleuca

Author:
  • J Rether
  • G Erkel
  • Olov Sterner
  • T Anke
Publishing year: 2005
Language: English
Pages: 478-484
Publication/Series: Zeitschrift fuer Naturforschung. Section C: A Journal of Biosciences
Volume: 60c
Issue: 5-6
Document type: Journal article
Publisher: Verlag der Zeitschrift für Naturforschung

Abstract english

In a search for inhibitors of the inducible tumor necrosis factor-alpha (TNF-alpha) promoter activity and synthesis, a new chlorinated cyclopentenone was isolated from fermentations of the ascomycete Mollisia melaleuca. The structure was determined by a combination of spectroscopic techniques. The compound blocked the inducible human TNF-alpha promoter activity and synthesis with IC50-values of 2.5-5 mu g/ml (8.1-16.1 mu M). Studies on the mode of action of the compound revealed that the inhibition of TNF-alpha promoter activity is caused by an inhibition of the phosphorylation of the I kappa B protein which prevents the activation of the transcription factor NF-kappa B. No cytotoxic, antibacterial and antifungal activities could be observed up to 100 mu g/ml (323 mu m) of the compound.

Keywords

  • Organic Chemistry

Other

Published
  • ISSN: 0939-5075
Olov Sterner
E-mail: olov.sterner [at] science.lu.se

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