Contribution of Cage-Shaped Structure of Physalins to Their Mode of Action in Inhibition of NF-κB Activation
Contribution of Cage-Shaped Structure of Physalins to Their Mode of Action in Inhibition of NF-κB Activation
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DOI：
10.1021/ml400144e
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发表时间：
2013-08-01
影响因子：
4.2
通讯作者：
Sodeoka, Mikiko
中科院分区：
文献类型：
--
作者：
Ozawa, Masaaki;Morita, Masaki;Sodeoka, Mikiko
构建了一个含氧天然类固醇的文库，包括酸浆素、睡茄内酯和perulactones，以及B型酸浆素的合成笼形右侧结构。抑制NF-κ B活化的SAR研究表明B环和含氧右侧部分结构的重要性。酸浆素和睡茄内酯的5 β，6 β-环氧衍生物显示出相似的NF-κ B活化抑制谱，并且似乎通过抑制I κ B α的磷酸化和降解作用于NF-κ B信号传导。相反，具有C5-C6烯烃官能度的B型酸浆素抑制位于I κ B α降解下游的RelA/p50蛋白二聚体的核转位和DNA结合，尽管具有相同AB环官能度的睡茄内酯没有。这些结果表明，这些类固醇的右侧部分结构影响其作用方式。
A library of oxygenated natural steroids, including physalins, withanolides, and perulactones, coupled with the synthetic cage-shaped right-side structure of type B physalins, was constructed. SAR studies for inhibition of NF-kappa B activation showed the importance of both the B-ring and the oxygenated right-side partial structure. The 5 beta,6 beta-epoxy derivatives of both physalins and withanolides showed similar profiles of inhibition of NF-kappa B activation and appeared to act on NF-kappa B signaling via inhibition of phosphorylation and degradation of I kappa B alpha. In contrast, type B physalins with C5-C6 olefin functionality inhibited nuclear translocation and DNA binding of RelA/p50 protein dimer, which lie downstream of I kappa B alpha degradation, although withanolides having the same AB-ring functionality did not. These results indicated that the right-side partial structure of these steroids influences their mode of action.