Institute of Biochemistry, University Medicine Berlin-Charité, Monbijoustrasse 2, 10117 Berlin, Germany.
Org Biomol Chem. 2010 Feb 21;8(4):828-34. doi: 10.1039/b918778b. Epub 2009 Dec 23.
Low molecular weight seleno-organic compounds exhibit glutathione peroxidase (GPx)-like activity; the well-known compound ebselen is being used in clinical trials as a stroke medication. Here, we describe the facile one-step synthesis of novel 5-selenized salicylic acid derivatives using selenium tetrachloride. The products were analyzed by spectroscopic studies including (77)Se-NMR and some were subjected to X-ray structure determination. Several products were identified as selective inhibitors of the pro-inflammatory 5-lipoxygenase (LOX) but had little effect on the catalytic activity of 12/15-LOX, which has been implicated in the synthesis of anti-inflammatory mediators. Such isoform-specificity (specificity coefficient >120) has not been reported before for any seleno-organic compound. In addition, synthesis products exhibited GPx-like activity, which was higher than that of ebselen for some derivatives.
低分子量硒有机化合物具有谷胱甘肽过氧化物酶 (GPx) 样活性；著名的化合物依布硒啉正在临床试验中被用作中风药物。在这里，我们描述了使用四氯化硒简便地一步合成新型 5-硒代水杨酸衍生物。通过包括 (77)Se-NMR 在内的光谱研究对产物进行了分析，并且对一些产物进行了 X 射线结构测定。几种产物被鉴定为促炎 5-脂氧合酶 (LOX) 的选择性抑制剂，但对催化活性 12/15-LOX 的影响很小，12/15-LOX 与抗炎介质的合成有关。这种同工酶特异性（特异性系数>120）以前从未在任何硒有机化合物中报道过。此外，合成产物表现出 GPx 样活性，对于一些衍生物而言，其活性高于依布硒啉。
