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Enzymatic Synthesis of Epoxidized Metabolites of Docosahexaenoic, Eicosapentaenoic, and Arachidonic Acids
Published on: June 28, 2019
5-Selenization of salicylic acid derivatives yielded isoform-specific 5-lipoxygenase inhibitors
Sun-Chol Yu1, Hartmut Kuhn, Constantin-Gabriel Daniliuc
1Institute of Biochemistry, University Medicine Berlin-Charité, Monbijoustrasse 2, 10117 Berlin, Germany.
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.
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