Five new secondary metabolites, modiolides D-G (1-4) and 1-(2,5-dihydroxyphenyl)-3-methoxy-butan-1-one (8), one new natural product, 1-(2,5-dihydroxyphenyl)-3-hydroxybutan-1-one (7), along with three known compounds, modiolides A (5) and B (6), and 1-(2,5-dihydroxyphenyl)-2-buten-1-one (9) were isolated from a fermentation culture of the marine endophytic fungus Paraconiothyrium sp. VK-13. Their chemical structures were elucidated by the NMR and MS spectroscopic analysis as well as the modified Mosher's method. Compounds 7 and 9 inhibited the overproduction of proinflammatory mediators NO and PGE₂ in LPS-stimulated RAW264.7 cells, with IC₅₀ values ranging from 3.9 to 12.5 µM. The inhibitory effects of 7 and 9 on the release of NO and PGE₂ were correlated with their significant suppression of iNOS and COX-2 protein expression, respectively. Furthermore, both compounds 7 and 9 inhibited the mRNA expression of proinflammatory cytokines, including TNF-α, IL-1β, IL-6, and IL-12, with IC₅₀ values in a range of 2.4-12.5 µM.

中文翻译：

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来自海洋真菌Paraconiothyrium sp。的大环内酯和酚类代谢物。VK-13具有抗炎活性。

五种新的次生代谢产物，甘氨酸单酚DG（1-4）和1-（2,5-二羟基苯基）-3-甲氧基-丁丹-1-酮（8），一种新的天然产物1-（2,5-二羟基苯基） -3-羟基丁烷-1-酮（7）以及三种已知的化合物，扁桃酸酯A（5）和B（6）和1-（2,5-二羟基苯基）-2-丁烯-1-酮（9）分离自海洋内生真菌Paraconiothyrium sp。的发酵培养物。VK-13。通过NMR和MS光谱分析以及改进的Mosher方法阐明了它们的化学结构。化合物7和9抑制LPS刺激的RAW264.7细胞中促炎性介质NO和PGE ₂的过量产生，IC ₅₀值为3.9至12.5 µM。7和9对NO和PGE ₂释放的抑制作用分别与它们对iNOS和COX-2蛋白表达的显着抑制有关。此外，化合物7和9均抑制促炎细胞因子的mRNA表达，包括TNF-α，IL-1β，IL-6和IL-12，IC ₅₀值在2.4-12.5 µM的范围内。