Kynuramines, metabolites of melatonin and other indoles: the resurrection of an almost forgotten class of biogenic amines

Abstract

: Kynuramines represent their own class of biogenic amines. They are formed either by decarboxylation of kynurenines or pyrrole ring cleavage of indoleamines. N2‐formylated compounds formed in this last reaction can be deformylated either enzymatically by arylamine formamidases or hemoperoxidases, or photochemically. The earlier literature mainly focussed on cardiovascular effects of kynuramine, 5‐hydroxykynuramine and their N1,N1‐dimethylated analogs, including indirect effects via release of catecholamines or acetylcholine and interference with serotonin receptors. After the discovery of N1‐acetyl‐N2‐formyl‐5‐methoxykynuramine (AFMK) and N1‐acetyl‐5‐methoxykynuramine (AMK) as major brain metabolites of melatonin, these compounds became of particular interest. They were shown to be produced enzymatically, pseudoenzymatically, by various free radical‐mediated and via photochemical processes. In recent years, AFMK and AMK were shown to scavenge reactive oxygen and nitrogen species, thereby forming several newly discovered 3‐indolinone, cinnolinone and quinazoline compounds, and to protect tissues from damage by reactive intermediates in various models. AMK is of special interest due to its properties as a potent cyclooxygenase inhibitor, NO scavenger forming a stable nitrosation product, inhibitor and/or downregulator of neuronal and inducible NO synthases, and a mitochondrial metabolism modulator. AMK easily interacts with aromates, forms adducts with tyrosyl and tryptophanyl residues, and may modify proteins.

Melatonin Metabolism in the Central Nervous System

“…The relative contribution of concurrent catabolic pathways may be strongly influenced by conditions of inflammation and oxidative stress [50]. This is supported by findings on elevated levels of melatonin's oxidation product N 1 -acetyl-N 2 -formyl-5-methoxykynuramine (AFMK) in the cerebrospinal fluid of patients with meningitis [125].…”

Alleviating effects of melatonin on oxidative changes in the testes and pituitary glands evoked by subacute chlorpyrifos administration in Wistar rats

“…Melatonin along with its metabolites has been shown to scavenge reactive oxygen species (ROS) or reactive nitrogen species (RNS) [26] . This cascade reaction makes melatonin a highly effective antioxidant, even at low concentrations, in protecting cells from oxidative stress [27] .…”

Efeito de diferentes concentrações de melatonina em espermatozoides de carneiros sobre estresse oxidativo após criopreservação

“…O efeito antioxidante da melatonina em vários tipos de células tem sido frequentemente explicado devido a sua capacidade de neutralizar uma grande quantidade de radicais livres tóxicos (Peyrot & Ducrocq 2008, Hardeland et al 2009) e influenciar a expressão gênica de enzimas antioxidantes, aumentando os níveis de RNA mensageiro e de proteínas dessas enzimas (Reiter et al 2000). Vários autores têm relatado que a melatonina apresenta efeito benéfico sobre a preservação de espermatozoides de mamíferos, melhorando seus parâmetros funcionais (Rao & Gangadharan 2008, Casao et al 2010, Du Plessis et al 2010, Ashrafi et al 2013.…”