Hydrophobicity and glutathione peroxidase-like activity of substituted salicyloyl-5-seleninic acids: Re-investigations on aromatic selenium compounds based on their hydrophobicity

Abstract Previously we have shown that some of 5-selenized salicylic acid derivatives exhibit glutathione peroxidase (GPx)-like activities higher than or equal to ebselen [Yu et al., Chem. Eur. J. , 2008, 14 , 7066; Org. Biomol. Chem. , 2010, 8 , 828]. For understanding the absence of GPx-like activity of the homologue of 5-seleninic anhydride of salicyloylglycine with a loger side chain, we have further synthesized 19 new derivatives (5-seleninic acids of methyl or phenyl salicylates, N -salicyloyl ω-carboxyalkylamines or N -salicyloyl alkyl/phenyl amines, and some of their diselenides). Some of the 5-seleninic acids which carry long side chains or cyclohexyl group have exerted no GPx–like activity, irrespective of whether they are derived from ω-carboxyalkylamines or simple alkylamines. Such lacks of GPx-like activity let us quantitatively relate the GPx-like activities of the congeners of the above 3 series with their hydrophobicity (ClogP), which showed satisfactory correlations in each series. The molecular hydrophobicity was then extensively applied to diverse known aromatic selenium GPx mimics including diaryl diselenides and ebselen derivatives to explain their GPx-like activities in comparably quantitative mode, which could be helpful in designing new improved GPx mimic analogues in each series.