Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 54538, Korea.
College of Medical and Life Sciences, Silla University, Busan 46958, Korea.
Mar Drugs. 2020 May 9;18(5):247. doi: 10.3390/md18050247.
A chemical investigation of the marine-derived fungal strain (SF-7123) revealed a new citromycetin (polyketide) derivative () and four known secondary fungal metabolites, i.e, neuchromenin (), asterric acid (), myxotrichin C (), and deoxyfunicone (). The structures of these metabolites were identified primarily by extensive analysis of their spectroscopic data, including NMR and MS data. Results from the initial screening of anti-inflammatory effects showed that , , and possessed inhibitory activity against the excessive production of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated BV2 microglial cells, with IC values of 2.7 µM, 28.1 µM, and 10.6 µM, respectively. Compounds , , and also inhibited the excessive production of NO, with IC values of 4.7 µM, 41.5 µM, and 40.1 µM, respectively, in LPS-stimulated RAW264.7 macrophage cells. In addition, these compounds inhibited LPS-induced overproduction of prostaglandin E in both cellular models. Further investigation of the most active compound () revealed that these anti-inflammatory effects were associated with a suppressive effect on the over-expression of inducible nitric oxide synthase and cyclooxygenase-2. Finally, we showed that the anti-inflammatory effects of compound were mediated via the downregulation of inflammation-related pathways such as those dependent on nuclear factor kappa B and p38 mitogen-activated protein kinase in LPS-stimulated BV2 and RAW264.7 cells. In the evaluation of the inhibitory effects of the isolated compounds on protein tyrosine phosphate 1B (PTP1B) activity, compound was identified as a noncompetitive inhibitor of PTP1B, with an IC value of 19.2 µM, and compound was shown to inhibit the activity of PTP1B, with an IC value of 24.3 µM, by binding to the active site of the enzyme. Taken together, this study demonstrates the potential value of marine-derived fungal isolates as a bioresource for bioactive compounds.
海洋来源真菌菌株 SF-7123 的化学成分研究揭示了一种新的 citromycetin（聚酮）衍生物 () 和四种已知的次级真菌代谢产物，即 neuchromenin ()、asterric acid ()、myxotrichin C () 和 deoxyfunicone ()。这些代谢产物的结构主要通过对其光谱数据（包括 NMR 和 MS 数据）的广泛分析来确定。抗炎作用的初步筛选结果表明， 、 和 对脂多糖 (LPS) 刺激的 BV2 小胶质细胞中一氧化氮 (NO) 的过度产生具有抑制活性，其 IC 值分别为 2.7 µM、28.1 µM 和 10.6 µM。化合物 、 、和 也抑制 LPS 刺激的 RAW264.7 巨噬细胞中 NO 的过度产生，其 IC 值分别为 4.7 µM、41.5 µM 和 40.1 µM。此外，这些化合物抑制两种细胞模型中 LPS 诱导的前列腺素 E 的过度产生。对最活跃的化合物 () 的进一步研究表明，这些抗炎作用与抑制诱导型一氧化氮合酶和环氧化酶-2 的过度表达有关。最后，我们表明，化合物 的抗炎作用是通过下调 LPS 刺激的 BV2 和 RAW264.7 细胞中与核因子 kappa B 和 p38 丝裂原活化蛋白激酶相关的炎症相关途径来介导的。在评估分离化合物对蛋白酪氨酸磷酸酶 1B (PTP1B) 活性的抑制作用时，化合物 被鉴定为 PTP1B 的非竞争性抑制剂，其 IC 值为 19.2 µM，化合物 被证明通过与酶的活性位点结合来抑制 PTP1B 的活性，其 IC 值为 24.3 µM。综上所述，这项研究表明海洋来源真菌分离物作为生物活性化合物的生物资源具有潜在价值。
