With a view to elucidating the structural requisites for effective anti-nitrosating properties in plant polyphenolics and their metabolites, we have undertaken a comparative investigation of the nitrite scavenging effects of representative catechol derivs. of dietary relevance in the 2,3-diaminonaphthalene (DAN) nitrosation and tyrosine nitration assays. Compds. tested included caffeic acid (1), chlorogenic acid (2), piceatannol (3), hydroxytyrosol (4), and the corresponding S-glutathionyl conjugates 5-8, which were prepd. using either tyrosinase (5 and 6) or a novel, o-iodoxybenzoic acid (IBX)-based oxygenation/conjugation methodol. (7b and 8). In the DAN nitrosation assay at pH 4.0, the rank order of inhibitory activities was found to be 5-S-glutathionylpiceatannol (7b) > 3 > 1 > 2 > 2-S-glutathionylcaffeic acid (5) > 2-S-glutathionylchlorogenic acid (6) > 4 » 5-S-glutathionylhydroxytyrosol (8). Quite unexpectedly, in the tyrosine nitration assay in 0.5 M HCl, 2 was the most efficient inhibitor followed by 1 > 4 > 3 > 7b » 5 > 8 > 6. Under the assay conditions, the glutathionyl conjugates were usually consumed at faster rates than the parent catechols (decompn. rates: 3 > 1 > 4 > 2). The 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) assay indicated that the most effective hydrogen donors were 4 > 7b > 1 » 3. Overall, these results indicated that catechol compds. and their glutathionyl conjugates may exhibit profoundly different inhibitory properties depending on the specific conditions of the assay, including esp. pH, and that their anti-nitrosating properties do not correlate tout-court with their hydrogen donor capacity. The glutathionyl-piceatannol conjugate 7b was found to be one of the most potent inhibitors in the physiol. relevant DAN assay and may provide a new structural lead for the design of effective anti-nitrosating agents based on dietary polyphenolic compds.
Plant Catechols and Their S-Glutathionyl Conjugates as Antinitrosating Agents: Expedient Synthesis and Remarkable Potency of 5-S-Glutathionylpiceatannol
D'ISCHIA M.
2008
Abstract
With a view to elucidating the structural requisites for effective anti-nitrosating properties in plant polyphenolics and their metabolites, we have undertaken a comparative investigation of the nitrite scavenging effects of representative catechol derivs. of dietary relevance in the 2,3-diaminonaphthalene (DAN) nitrosation and tyrosine nitration assays. Compds. tested included caffeic acid (1), chlorogenic acid (2), piceatannol (3), hydroxytyrosol (4), and the corresponding S-glutathionyl conjugates 5-8, which were prepd. using either tyrosinase (5 and 6) or a novel, o-iodoxybenzoic acid (IBX)-based oxygenation/conjugation methodol. (7b and 8). In the DAN nitrosation assay at pH 4.0, the rank order of inhibitory activities was found to be 5-S-glutathionylpiceatannol (7b) > 3 > 1 > 2 > 2-S-glutathionylcaffeic acid (5) > 2-S-glutathionylchlorogenic acid (6) > 4 » 5-S-glutathionylhydroxytyrosol (8). Quite unexpectedly, in the tyrosine nitration assay in 0.5 M HCl, 2 was the most efficient inhibitor followed by 1 > 4 > 3 > 7b » 5 > 8 > 6. Under the assay conditions, the glutathionyl conjugates were usually consumed at faster rates than the parent catechols (decompn. rates: 3 > 1 > 4 > 2). The 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) assay indicated that the most effective hydrogen donors were 4 > 7b > 1 » 3. Overall, these results indicated that catechol compds. and their glutathionyl conjugates may exhibit profoundly different inhibitory properties depending on the specific conditions of the assay, including esp. pH, and that their anti-nitrosating properties do not correlate tout-court with their hydrogen donor capacity. The glutathionyl-piceatannol conjugate 7b was found to be one of the most potent inhibitors in the physiol. relevant DAN assay and may provide a new structural lead for the design of effective anti-nitrosating agents based on dietary polyphenolic compds.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
