Indole Melatonin Agonists and Antagonists Derived by Shifting the Melatonin Side Chain from the C-3 to the N-1 or to the C-2 Indole Position

Tarzia, Giorgio; Diamantini, Giuseppe; Spadoni, Gilberto

doi:10.1159/000014565

Cited by 8 publications

(6 citation statements)

References 27 publications

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“…The results indicate that this isomer has a similar affinity binding with melatonin membrane receptors as melatonin itself and it also exhibits full agonistic activity in lowering intracellular cAMP levels. In a follow‐up study [100], this group observed that the synthetic MIs induced completely different biological consequences after binding to melatonin membrane receptors. They behaved as agonists or as antagonists depending on the position of the chain A in the indole ring.…”

Section: Discussionmentioning

confidence: 99%

Emergence of naturally occurring melatonin isomers and their proposed nomenclature

Tan

Hardeland

Manchester

et al. 2012

Journal of Pineal Research

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: Melatonin was considered to be the sole member of this natural family. The emergence of naturally occurring melatonin isomers (MIs) has opened an exciting new research area. Currently, several MIs have been identified in wine, and these molecules are believed to be synthesized by either yeasts or bacteria. A tentative nomenclature for the MIs is proposed in this article. It will be important to explore whether all organisms have the capacity to synthesize MIs, especially under the conditions of environmental stress. These isomers probably share many of the biological functions of melatonin, but their activities seem to exceed those of melatonin. On basis of the limited available information, it seems that MIs differ in their biosynthetic pathways from melatonin. Especially in those compounds in which the aliphatic side chain is not attached to ring atom 3, the starting material may not be tryptophan. Also, the metabolic pathways of MIs remain unknown. This, therefore, is another promising area of research to explore. It is our hypothesis that MIs would increase the performance of yeasts and probiotic bacteria during the processes of fermentation. Therefore, yeasts producing elevated levels of these isomers might have a superior alcohol tolerance and be able to produce higher levels of alcohol. This can be tested by comparing existing yeast strains differing in alcohol tolerance. Selection for MIs may become a strategy for isolating more resistant yeast and Lactobacillus strains, which can be of interest for industrial alcohol production and quality improvements in bacterially fermented foods such as kimchi.

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Section: Discussionmentioning

confidence: 99%

Emergence of naturally occurring melatonin isomers and their proposed nomenclature

Tan

Hardeland

Manchester

et al. 2012

Journal of Pineal Research

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“…Other fascinating issues regard the biological functions of melatonin isomers and their possible correlation with the healthy potential of red wine. Studies on synthetic isomers showed that the position of the two side chains may affect both receptor‐dependent and receptor‐independent melatonin mechanisms of action, including the binding to melatonin membrane receptors, cytoprotective and antioxidant activities . Interestingly, it was reported that changing the position of either side chain A or side chain M in the indole ring results in marked alteration in isomer antioxidant and cytoprotective properties.…”

Section: Discussionmentioning

confidence: 99%

Melatonin, melatonin isomers and stilbenes in Italian traditional grape products and their antiradical capacity

Vitalini

Gardana

Simonetti

et al. 2012

Journal of Pineal Research

105

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Although polyphenols represent the paradigm of the health-promoting effects ascribed to grape products, recently, attention has been paid to dietary melatonin, significantly present in Mediterranean foods. In this work, we measured melatonin, its isomers, stilbenes (trans- and cis-resveratrol and their glucosides, piceids) and total polyphenols in some different grape products (red, white and dessert wines, grape juices and Modena balsamic vinegars) of distinct Italian areas. We also evaluated their antiradical activity by DPPH(·) and ABTS(·+) assays. For indoleamine analysis, the separation was carried out on a 1.7-μm C18 BEH column and the detection performed by means of mass spectrometry with electrospray ionization in positive ion mode with multiple reaction monitoring. The confirmation of the peak identity was accomplished by injection into the high-resolution system (Orbitrap) using accurate mass measurements (error below 1.0 ppm). Mass spectrometry analyses revealed, for the first time, the presence of melatonin in dessert wines and balsamic vinegars, as well as the occurrence of three different melatonin isomers in grape products.

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“…Green plants provide both oxygen and nutrients, and some of these nutrients are important antioxidants. In our opinion, in addition to the clinical applications of receptor-mediated actions [15,16,[109][110][111][112][113][114][115][116][117][118][119][120][121][122][123], the therapeutic potential of melatonin and analogs [38,[124][125][126] as an antioxidative protective agent [18,19,22,29,30,43,46,72,75,101,[127][128][129][130][131][132][133][134][135][136][137][138] should be further explored.…”

Section: Discussionmentioning

confidence: 99%

Significance of Melatonin in Antioxidative Defense System: Reactions and Products

et al. 2000

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Melatonin is a potent endogenous free radical scavenger, actions that are independent of its many receptor-mediated effects. In the last several years, hundreds of publications have confirmed that melatonin is a broad-spectrum antioxidant. Melatonin has been reported to scavenge hydrogen peroxide (H₂O₂), hydroxyl radical (HO·), nitric oxide (NO·), peroxynitrite anion (ONOO^–), hypochlorous acid (HOCl), singlet oxygen (¹O₂), superoxide anion (O₂^–·) and peroxyl radical (LOO·), although the validity of its ability to scavenge O₂^–· and LOO· is debatable. Regardless of the radicals scavenged, melatonin prevents oxidative damage at the level of cells, tissues, organs and organisms. The antioxidative mechanisms of melatonin seem different from classical antioxidants such as vitamin C, vitamin E and glutathione. As electron donors, classical antioxidants undergo redox cycling; thus, they have the potential to promote oxidation as well as prevent it. Melatonin, as an electron-rich molecule, may interact with free radicals via an additive reaction to form several stable end-products which are excreted in the urine. Melatonin does not undergo redox cycling and, thus, does not promote oxidation as shown under a variety of experimental conditions. From this point of view, melatonin can be considered a suicidal or terminal antioxidant which distinguishes it from the opportunistic antioxidants. Interestingly, the ability of melatonin to scavenge free radicals is not in a ratio of mole to mole. Indeed, one melatonin molecule scavenges two HO·. Also, its secondary and tertiary metabolites, for example, N¹-acetyl-N²-formyl-5-methoxykynuramine, N-acetyl-5-methoxykynuramine and 6-hydroxymelatonin, which are believed to be generated when melatonin interacts with free radicals, are also regarded as effective free radical scavengers. The continuous free radical scavenging potential of the original molecule (melatonin) and its metabolites may be defined as a scavenging cascade reaction. Melatonin also synergizes with vitamin C, vitamin E and glutathione in the scavenging of free radicals. Melatonin has been detected in vegetables, fruits and a variety of herbs. In some plants, especially in flowers and seeds (the reproductive organs which are most vulnerable to oxidative insults), melatonin concentrations are several orders of magnitude higher than measured in the blood of vertebrates. Melatonin in plants not only provides an alternative exogenous source of melatonin for herbivores but also suggests that melatonin may be an important antioxidant in plants which protects them from a hostile environment that includes extreme heat, cold and pollution, all of which generate free radicals.

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Indole Melatonin Agonists and Antagonists Derived by Shifting the Melatonin Side Chain from the C-3 to the N-1 or to the C-2 Indole Position

Cited by 8 publications

References 27 publications

Emergence of naturally occurring melatonin isomers and their proposed nomenclature

Emergence of naturally occurring melatonin isomers and their proposed nomenclature

Melatonin, melatonin isomers and stilbenes in Italian traditional grape products and their antiradical capacity

Significance of Melatonin in Antioxidative Defense System: Reactions and Products

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