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

Abstract

In a search for inhibitors of the inducible tumor necrosis factor-α (TNF-α) 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-α promoter activity and synthesis with IC50-values of 2.5-5 μg/ml (8.1-16.1 μM). Studies on the mode of action of the compound revealed that the inhibition of TNF-α promoter activity is caused by an inhibition of the phosphorylation of the IκB protein which prevents the activation of the transcription factor NF-κB. No cytotoxic, antibacterial and antifungal activities could be observed up to 100 μg/ml (323 μM) of the compound. © 2005 Verlag der Zeitschrift für Naturforschung.