Anti-inflammatory dihydroxanthones from a Diaporthe species

In a search for anti-inflammatory compounds from fungi inhibiting the promoter activity of the small chemokine CXCL10 (Interferon-inducible protein 10, IP-10) as a pro-inflammatory marker gene, the new dihydroxanthone methyl (1 , 2 )-1,2,8-trihydroxy-6-(hydroxymethyl)-9-oxo-2,9-dihydro-1 -xanthene-1-carboxylate ( ) and the previously described dihydroxanthone AGI-B4 ( ) were isolated from fermentations of a species. The structures of the compounds were elucidated by a combination of one- and two-dimensional NMR spectroscopy, mass spectrometry, and calculations using density functional theory (DFT). Compounds and inhibited the LPS/IFNγ induced CXCL10 promoter activity in transiently transfected human MonoMac6 cells in a dose-dependent manner with IC values of 4.1 µM (±0.2 µM) and 1.0 µM (±0.06 µM) respectively. Moreover, compounds and reduced mRNA levels and synthesis of pro-inflammatory mediators such as cytokines and chemokines in LPS/IFNγ stimulated MonoMac6 cells by interfering with the Stat1 and NFκB pathway.