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 (1R, 2R)-1,2,8-trihydroxy-6-(hydroxymethyl)-9-oxo-2,9-dihydro-1H-xanthene-1-carboxylate (2) and the previously described dihydroxanthone AGI-B4 (1) were isolated from fermentations of a Diaporthe 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 1 and 2 inhibited the LPS/IFNγ induced CXCL10 promoter activity in transiently transfected human MonoMac6 cells in a dose-dependent manner with IC50 values of 4.1 µM (±0.2 µM) and 1.0 µM (±0.06 µM) respectively. Moreover, compounds 1 and 2 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.

中文翻译：

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来自 Diaporthe 物种的抗炎二氢氧杂蒽酮

为了从真菌中寻找抑制小趋化因子 CXCL10（干扰素诱导蛋白 10，IP-10）作为促炎标记基因的启动子活性的抗炎化合物，新的甲基二氢蒽酮（1R, 2R)-1,2,8-trihydroxy-6-(hydroxymethyl)-9-oxo-2,9-dihydro-1H-xanthene-1-carboxylate (2) 和先前描述的二羟基蒽酮 AGI-B4 (1) 从迪亚波尔特物种。通过结合一维和二维核磁共振光谱、质谱和使用密度泛函理论 (DFT) 的计算来阐明化合物的结构。化合物 1 和 2 在瞬时转染的人 MonoMac6 细胞中以剂量依赖性方式抑制 LPS/IFNγ 诱导的 CXCL10 启动子活性，具有 IC50值分别为 4.1 µM (±0.2 µM) 和 1.0 µM (±0.06 µM)。此外，化合物 1 和 2 通过干扰 Stat1 和 NFκB 通路降低了 LPS/IFNγ 中的 mRNA 水平和促炎介质（如细胞因子和趋化因子）的合成，从而刺激了 MonoMac6 细胞。