Nuclear Factor-κB Mediated Inhibition of Cytokine Production by Imidazoline Scaffolds
Nuclear Factor-κB Mediated Inhibition of Cytokine Production by Imidazoline Scaffolds
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DOI：
10.1021/jm8013162
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发表时间：
2009-03-12
影响因子：
7.3
通讯作者：
Tepe, Jetze J.
中科院分区：
文献类型：
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作者：
Kahlon, Daljinder K.;Lansdell, Theresa A.;Tepe, Jetze J.
哺乳动物核转录因子NF-kappa B负责多种细胞因子的转录，包括促炎细胞因子肿瘤坏死因子α (tnf - α)和白细胞介素6 （IL-6）。促炎细胞因子水平升高在炎性疾病如类风湿关节炎（RA）的发病机制中起重要作用。因此，抑制促炎转录因子nf - κ B已被确定为RA的可能治疗方法。我们在此描述了一系列咪唑啉基支架的合成和生物活性，作为细胞培养中nf - κ B介导的基因转录的有效抑制剂，以及白细胞介素1 β (IL-1 β)刺激的人血液中tnf - α和IL-6产生的抑制剂。
The mammalian nuclear transcription factor NF-kappa B is responsible for the transcription of multiple cytokines, including the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6). Elevated levels of pro-inflammatory cytokines play an important role in the pathogenesis of inflammatory disorders such as rheumatoid arthritis (RA). Inhibition of the pro-inflammatory transcription factor NF-kappa B has therefore been identified as a possible therapeutic treatment for RA. We describe herein the synthesis and biological activity of a series of imidazoline-based scaffolds as potent inhibitors of NF-kappa B mediated gene transcription in cell culture as well as inhibitors of TNF-alpha and IL-6 production in interleukin 1 beta (IL-1 beta) stimulated human blood.