On the free radical scavenging activities of melatonin's metabolites, AFMK and AMK

Annia Galano, Dun Xian Tan, Russel J Reiter

Research output: Contribution to journalArticle

479 Citations (Scopus)

Abstract

The reactions of N1-acetyl-N2-formyl-5- methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK) with OH, OOH, and •OOCCl3 radicals have been studied using the density functional theory. Three mechanisms of reaction have been considered: radical adduct formation (RAF), hydrogen transfer (HT), and single electron transfer (SET). Their relative importance for the free radical scavenging activity of AFMK and AMK has been assessed. It was found that AFMK and AMK react with •OH at diffusion-limited rates, regardless of the polarity of the environment, which supports their excellent •OH radical scavenging activity. Both compounds were found to be also very efficient for scavenging •OOCCl3, but rather ineffective for scavenging •OOH. Regarding their relative activity, it was found that AFMK systematically is a poorer scavenger than AMK and melatonin. In aqueous solution, AMK was found to react faster than melatonin with all the studied free radicals, while in nonpolar environments, the relative efficiency of AMK and melatonin as free radical scavengers depends on the radical with which they are reacting. Under such conditions, melatonin is predicted to be a better •OOH and •OOCCl3 scavenger than AMK, while AMK is predicted to be slightly better than melatonin for scavenging •OH. Accordingly it seems that melatonin and its metabolite AMK constitute an efficient team of scavengers able of deactivating a wide variety of reactive oxygen species, under different conditions. Thus, the presented results support the continuous protection exerted by melatonin, through the free radical scavenging cascade.

Original languageEnglish (US)
Pages (from-to)245-257
Number of pages13
JournalJournal of Pineal Research
Volume54
Issue number3
DOIs
StatePublished - Apr 2013

Fingerprint

Melatonin
Free Radicals
Free Radical Scavengers
N-(2-(1-acetyl-5-methoxy-1H-indol-3-yl)ethyl)acetamide
Hydrogen
Reactive Oxygen Species
Electrons

Keywords

  • antioxidant
  • kinetics
  • mechanism of reaction
  • N-acetyl-5- methoxykynuramine
  • N-acetyl-N-formyl-5-methoxykynuramine
  • rate constants

ASJC Scopus subject areas

  • Endocrinology

Cite this

On the free radical scavenging activities of melatonin's metabolites, AFMK and AMK. / Galano, Annia; Tan, Dun Xian; Reiter, Russel J.

In: Journal of Pineal Research, Vol. 54, No. 3, 04.2013, p. 245-257.

Research output: Contribution to journalArticle

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AB - The reactions of N1-acetyl-N2-formyl-5- methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK) with •OH, •OOH, and •OOCCl3 radicals have been studied using the density functional theory. Three mechanisms of reaction have been considered: radical adduct formation (RAF), hydrogen transfer (HT), and single electron transfer (SET). Their relative importance for the free radical scavenging activity of AFMK and AMK has been assessed. It was found that AFMK and AMK react with •OH at diffusion-limited rates, regardless of the polarity of the environment, which supports their excellent •OH radical scavenging activity. Both compounds were found to be also very efficient for scavenging •OOCCl3, but rather ineffective for scavenging •OOH. Regarding their relative activity, it was found that AFMK systematically is a poorer scavenger than AMK and melatonin. In aqueous solution, AMK was found to react faster than melatonin with all the studied free radicals, while in nonpolar environments, the relative efficiency of AMK and melatonin as free radical scavengers depends on the radical with which they are reacting. Under such conditions, melatonin is predicted to be a better •OOH and •OOCCl3 scavenger than AMK, while AMK is predicted to be slightly better than melatonin for scavenging •OH. Accordingly it seems that melatonin and its metabolite AMK constitute an efficient team of scavengers able of deactivating a wide variety of reactive oxygen species, under different conditions. Thus, the presented results support the continuous protection exerted by melatonin, through the free radical scavenging cascade.

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