Structural-activity relationship study of highly-functionalized imidazolines as potent inhibitors of nuclear transcription factor-κB mediated IL-6 production
Structural-activity relationship study of highly-functionalized imidazolines as potent inhibitors of nuclear transcription factor-κB mediated IL-6 production
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DOI：
10.1016/j.bmc.2009.03.002
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发表时间：
2009-04-15
影响因子：
3.5
通讯作者：
Tepe, Jetze J.
中科院分区：
文献类型：
--
作者：
Kahlon, Daljinder K.;Lansdell, Theresa A.;Tepe, Jetze J.
我们在此描述了基于咪唑啉的NF-κ B抑制剂的小文库的合成和抗炎性质。评价咪唑啉核心结构上各种取代基抑制NF-κ B介导的IL-6产生的能力的结构-活性关系。通过将基于琼脂糖酶的NF-κ B报告基因测定与IL-1 β刺激的人血液中IL-6产生的抑制相关联来进行支架的优化。发现几种衍生物在IL-1 β刺激的人血液中以纳摩尔范围抑制NF-κ B介导的IL-6产生。(C)2009爱思唯尔有限公司保留所有权利。
We herein describe the synthesis and anti-inflammatory properties of a small library of imidazoline-based NF-kappa B inhibitors. The structure-activity relationship of various substituents on an imidazoline core structure was evaluated for the ability to inhibit NF-kappa B mediated IL-6 production. Optimization of the scaffolds was pursued by correlating luciferase-based NF-kappa B reporter assays with inhibition of IL-6 production in IL-1 beta stimulated human blood. Several derivatives were found to inhibit NF-kappa B mediated IL-6 production in the nanomolar range in IL-1 beta stimulated human blood. (C) 2009 Elsevier Ltd. All rights reserved.