首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >Development of a novel furocoumarin derivative inhibiting NF-kappaB dependent biological functions: design, synthesis and biological effects.
【24h】

Development of a novel furocoumarin derivative inhibiting NF-kappaB dependent biological functions: design, synthesis and biological effects.

机译:新型呋喃香豆素衍生物抑制NF-κB依赖性生物学功能的开发:设计,合成和生物学作用。

获取原文
获取原文并翻译 | 示例
           

摘要

Nuclear Factor kappaB (NF-kappaB) plays a very important role in the control of gene expression and is deeply involved in several human pathologies. Accordingly, molecules targeting NF-kappaB dependent biological functions are considered of great interest. Virtual screening of furocoumarin libraries against NF-kappaB p50 allowed to rank compounds in respect to their expected ability to bind NF-kappaB and the identified compound might be considered for the development of analogs to be tested for biological activity on inhibition of NF-kappaB/DNA complex formation. The data reported in the present paper suggest that, following this approach, the best ranked compounds identified by virtual screening (a) strongly bind in silico to NF-kappaB and (b) efficiently inhibit the molecular interactions between (32)P-labeled NF-kappaB double stranded DNA and p50 or p50/p65 complex. These data allowed to develop a novel lead of great interest for inhibiting NF-kappaB dependent biological functions. This novel molecule (compound 2), bearing a methyl group in the 9 position of the psoralen nucleus, exhibits high efficiency in inhibiting NF-kappaB/DNA interactions. In addition, we found that compound 2 is a potent inhibitor of IL-8 gene expression in TNF-alpha treated IB3-1 cystic fibrosis cells. Taken together, our data indicate that compound 2 might find an important place in the set of molecules of interest for the development of pharmaceutical strategies against the inflammatory phenotype of cystic fibrosis.
机译:核因子κB(NF-kappaB)在控制基因表达中起着非常重要的作用,并深深地参与了多种人类病理学研究。因此,认为靶向NF-κB依赖性生物学功能的分子非常受关注。对呋喃香豆素文库针对NF-kappaB p50进行的虚拟筛选可对化合物预期的结合NF-kappaB的能力进行排名,并且可以考虑将鉴定出的化合物用于开发类似物以测试其对NF-kappaB抑制的生物学活性。 DNA复合物的形成。本文报道的数据表明,采用这种方法后,通过虚拟筛选鉴定出的最佳化合物(a)在计算机上与NF-kappaB牢固结合,(b)有效抑制(32)P标记的NF之间的分子相互作用。 -kappaB双链DNA和p50或p50 / p65复合物。这些数据允许开发出一种新颖的抑制NF-κB依赖性生物学功能的新线索。这种新颖的分子(化合物2)在补骨脂素核的9位带有一个甲基,在抑制NF-κB/ DNA相互作用方面表现出很高的效率。此外,我们发现化合物2是TNF-α处理的IB3-1囊性纤维化细胞中IL-8基因表达的有效抑制剂。两者合计,我们的数据表明化合物2可能会在感兴趣的分子集合中找到重要位置,以开发针对囊性纤维化炎性表型的药物策略。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号