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Melatonin and its metabolites as copper chelating agents and their role in inhibiting oxidative stress: a physicochemical analysis
Author(s) -
Galano Annia,
Medina Manuel E.,
Tan Dun Xian,
Reiter Russel J.
Publication year - 2015
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12196
Subject(s) - melatonin , chelation , oxidative stress , chemistry , copper , metabolite , deprotonation , stereochemistry , biochemistry , organic chemistry , biology , ion , endocrinology
The copper sequestering ability of melatonin and its metabolites cyclic 3‐hydroxymelatonin (3 OHM ), N 1 ‐acetyl‐ N 2 ‐formyl‐5‐methoxykynuramine ( AFMK ), and N 1 ‐acetyl‐5‐methoxykynuramine ( AMK ) was investigated within the frame of the Density Functional Theory. It was demonstrated that these compounds are capable of chelating copper ions, yielding stable complexes. The most likely chelation sites were identified. Two different mechanisms were modeled, the direct‐chelation mechanism ( DCM ) and the coupled‐deprotonation‐chelation mechanism ( CDCM ). It is proposed that, under physiological conditions, CDCM would be the main chelation route for Cu( II ). It was found that melatonin and its metabolites fully inhibited the oxidative stress induced by Cu( II )‐ascorbate mixtures, via Cu( II ) chelation. In the same way, melatonin, AFMK , and 3 OHM also prevented the first step of the Haber–Weiss reaction, consequently turning off the ˙ OH production via the Fenton reaction. Therefore, it is proposed that, in addition to the previously reported free radical scavenging cascade, melatonin is also involved in a concurrent ‘chelating cascade’, thereby contributing to a reduction in oxidative stress. 3 OHM was identified as the most efficient of the studied compounds for that purpose, supporting the important role of this metabolite in the beneficial effects of melatonin against oxidative stress.