Melatonin and its metabolites as copper chelating agents and their role in inhibiting oxidative stress: a physicochemical analysis

Annia Galano; Manuel E. Medina; Dun Xian Tan; Russel J. Reiter

doi:10.1111/jpi.12196

journal article Dec 12, 2014

Melatonin and its metabolites as copper chelating agents and their role in inhibiting oxidative stress: a physicochemical analysis

Annia Galano

Manuel E. Medina

Dun Xian Tan Russel J. Reiter

Journal of Pineal Research Vol. 58 No. 1 pp. 107-116 · Wiley

View at Publisher Save 10.1111/jpi.12196

Abstract

AbstractThe copper sequestering ability of melatonin and its metabolites cyclic 3‐hydroxymelatonin (3OHM), N1‐acetyl‐N2‐formyl‐5‐methoxykynuramine (AFMK), and N1‐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 3OHM 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. 3OHM 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.

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References

Details

Published: Dec 12, 2014
Vol/Issue: 58(1)
Pages: 107-116
License: View

Authors

A

Annia Galano

Departamento de Química Universidad Autónoma Metropolitana‐Iztapalapa México, D. F México

M

Manuel E. Medina

Departamento de Química Universidad Autónoma Metropolitana‐Iztapalapa México, D. F México

D

Dun Xian Tan

Department of Cellular and Structural Biology UT Health Science Center San Antonio TX USA

R

Russel J. Reiter

Department of Cellular and Structural Biology UT Health Science Center San Antonio TX USA

Funding

SEP-CONACYT Award: 167491

Cite This Article

Annia Galano, Manuel E. Medina, Dun Xian Tan, et al. (2014). Melatonin and its metabolites as copper chelating agents and their role in inhibiting oxidative stress: a physicochemical analysis. Journal of Pineal Research, 58(1), 107-116. https://doi.org/10.1111/jpi.12196

Melatonin and its metabolites as copper chelating agents and their role in inhibiting oxidative stress: a physicochemical analysis

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