Organic & Biomolecular Chemistry 2010-02-21

5-Selenization of salicylic acid derivatives yielded isoform-specific 5-lipoxygenase inhibitors.

Sun-Chol Yu, Hartmut Kuhn, Constantin-Gabriel Daniliuc, Igor Ivanov, Peter G Jones, Wolf-Walther du Mont

Index: Org. Biomol. Chem. 8(4) , 828-34, (2010)

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Abstract

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.