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In a search for compounds inhibiting the inducible TNF-αa promoter activity in T cells, a new spiro-compound, designated oxaspirodion, was isolated from fermentations of the ascomycete  Chaetomium subspirale . Oxaspirodion inhibited TNF-α promoter-driven luciferase reporter gene expression with an IC 50  value of 2.5 µg/ml (10 µM) in TPA/ionomycin-stimulated Jurkat T cells. Studies on the mode of action of the compound revealed that the inhibition of the TNF-α promoter activity is caused by an inhibition of the phosphorylation of the ERK1/2 kinases. In addition, oxaspirodion inhibited the activation of the transcription factor NF-κB, which is involved in the inducible expression of many proinflammatory genes.

Inhibition of inducible TNF-α expression by oxaspirodion, a novel spiro-compound from the ascomycete Chaetomium subspirale