Cycloepoxydon, 1-hydroxy-2-hydroxymethyl-3-pent-1-enylbenzene and 1-hydroxy-2-hydroxymethyl-3-pent-1,3-dienylbenzene, new inhibitors of eukaryotic signal transduction
Cycloepoxydon, 1-hydroxy-2-hydroxymethyl-3-pent-1-enylbenzene and 1-hydroxy-2-hydroxymethyl-3-pent-1,3-dienylbenzene, new inhibitors of eukaryotic signal transduction
复制标题
DOI：
10.7164/antibiotics.51.455
复制
发表时间：
1998-05-01
影响因子：
3.3
通讯作者：
Sterner, O
中科院分区：
文献类型：
--
作者：
Gehrt, A;Erkel, G;Sterner, O
在筛选以分泌性碱性磷酸酶（SEAP）为报告基因的COS-7细胞NF-kappa B和AP-1介导的信号转导途径的新抑制剂的过程中，从菌株45-93的发酵中分离到了三个新化合物：环环氧酮(1)、1-羟基-2-羟甲基-3-戊-1-烯基苯(2)和1-羟基-2-羟甲基-3-戊-1,3-二烯基苯(3)。环环氧酮抑制tpa诱导的NF-kappa B和AP-1介导的SEAP表达，IC50分别为1近似于2 μ g/ml（4.2近似于8.4 μ M）和3近似于5 μ g/ml（12.6近似于21 μ M）。1-羟基-2-羟甲基-3-戊-1-烯基苯(2)抑制tpa诱导的NF-kappa B和AP-1介导的SEAP表达，IC50分别为7 μ g/ml （36.4 μ M）和5 μ g/ml (26 μ M)， 3仅对AP-1有弱抑制作用，对NF-kappa B依赖性报告基因表达无影响。在COS-7和HeLa S3细胞中，电泳迁移转移实验表明，环环氧酮强烈地降低了TPA和tnf - α介导的NF-kappa B结合到一个高亲和力的一致序列，这是由于抑制抑制蛋白I kappa B的磷酸化。
In a screening for new inhibitors of NF-kappa B and AP-1 mediated signal transduction pathways in COS-7 cells using secreted alkaline phosphatase (SEAP) as a reporter gene three novel compounds, cycloepoxydon (1), 1-hydroxy-2-hydroxymethyl-3-pent-1-enylbenzene (2) and 1-hydroxy-2-hydroxymethyl-3-pent-1,3-dienylbenzene (3) were isolated from fermentations of the deuteromycete strain 45-93. Cycloepoxydon inhibits the TPA-induced NF-kappa B and AP-1 mediated SEAP expression with an IC50 of 1 similar to 2 mu g/ml (4.2 similar to 8.4 mu M) and 3 similar to 5 mu g/ml (12.6 similar to 21 mu M) respectively. 1-Hydroxy-2-hydroxymethyl-3-pent-1-enylbenzene (2) inhibits the TPA-induced NF-kappa B and AP-1 mediated SEAP expression with an IC50 of 7 mu g/ml (36.4 mu M) and 5 mu g/ml (26 mu M). 3 showed only a weak inhibition of the AP-1 and no influence on NF-kappa B dependent reporter gene expression. In COS-7 and HeLa S3 cells electrophoretic mobility shift assays showed that cycloepoxydon strongly reduced the TPA and TNF-alpha mediated binding of NF-kappa B to a high affinity consensus sequence which was due to the inhibition of phosphorylation of the inhibitory protein I kappa B.