Oxidative conjugation of chlorogenic acid with glutathione. Structural characterization of addition products and a new nitrite-Promoted pathway.
Chlorogenic acid (1), a cancer chemopreventive agent widely found in fruits, tea and coffee, undergoes efficient conjugation with glutathione (GSH), in the presence of horseradish peroxidase/H(2)O(2) or tyrosinase at pH 7.4, to yield three main adducts that have been isolated and identified as 2-S-glutathionylchlorogenic acid (3), 2,5-di-S-glutathionylchlorogenic acid (4) and 2,5,6-tri-S-glutathionylchlorogenic acid (5) by extensive NMR analysis. The same pattern of products could be obtained by reaction of 1 with GSH in the presence of nitrite ions in acetate buffer at pH 4. Mechanistic experiments suggested that oxidative conjugation reactions proceed by sequential nucleophilic attack of GSH on ortho-quinone intermediates. Overall, these results provide the first complete spectral characterization of the adducts generated by biomimetic oxidation of 1 in the presence of GSH, and disclose a new possible nitrite-mediated conjugation pathway of 1 with GSH at acidic pH of physiological relevance.
Panzella
Lucia
L
Department of Organic Chemistry and Biochemistry, University of Naples 'Federico II', Via Cinthia 4, I-80126 Naples, Italy.
Napolitano
Alessandra
A
d'Ischia
Marco
M
D002726:Chlorogenic Acid / Q000031:analogs & derivatives / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009573:Nitrites / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D011809:Quinones / Q000737:chemistry
D009573:Nitrites; D011809:Quinones; D002726:Chlorogenic Acid; D006735:Horseradish Peroxidase; D014442:Monophenol Monooxygenase; D005978:Glutathione