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[摘要]：7 that lacks Se鬃譔 or Se鬃譕 non-bonded interactions was synthesized. This compd. exhibits a four-fold higher glutathione peroxidase-like (GPx-like) activity than ebselen and inhibits plant and mammalian 12/15-lipoxygenases at lower micromolar concns. Because of these pharmacol. properties, 7 may constitute a new lead compd. for the development of anti-inflammatory low-mol.-wt. seleno-org. compds. Analyzing the redox products of 7 with glutathione (GSH) and tBuOOH, we identified three potential catalytic cycles (A, B, C) of GPx-like activity that are interconnected by key metabolites. To study the relative contribution of these cycles to the catalytic activity, we prepd. selected reaction intermediates and found that the activity of seleninic acid anhydride 7 and of the corresponding diselenide 11 and selenol 14 compds. were in the same range. In contrast, the GPx-like activity of monoselenide 9 was more than one order of magnitude lower. These data suggested that cycles A and B may constitute the major routes of GPx-like activity of 7, whereas cycle C may not significantly contribute to catalysis. |
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