Reactions of the melatonin metabolite N¹‐acetyl‐5‐methoxykynuramine with carbamoyl phosphate and related compounds

Abstract

N-[2-(6-methoxyquinazolin-4-yl)-ethyl] acetamide (MQA) is a compound formed from the melatonin metabolite N(1)-acetyl-5-methoxykynuramine (AMK). We followed MQA production in reaction systems containing various putative reaction partners, in the absence and presence of hydrogen peroxide and/or copper(II). Although MQA may be formally described as a condensation product of either N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK) with ammonia, or AMK with formamide, none of these combinations led to substantial quantities of MQA. However, MQA formation was observed in mixtures containing AMK, hydrogen peroxide, hydrogen carbonate and ammonia, or AMK, hydrogen peroxide, copper(II) and potentially carbamoylating agents, such as potassium cyanate or, more efficiently, carbamoyl phosphate. In the presence of hydrogen peroxide, copper(II) and carbamoyl phosphate, MQA was the major product obtained from AMK, but the omission of copper(II) mainly led to another metabolite, 3-acetamidomethyl-6-methoxycinnolinone (AMMC). This was caused by nitric oxide (NO) generated under oxidative conditions from carbamoyl phosphate, as shown by an NO spin trap. MQA formation with carbamoyl phosphate was not due to the possible decomposition product, formamide. The reaction of AMK with carbamoyl phosphate under oxidative conditions, in which inorganic phosphate and water are released and which differs from the typical process of carbamoylation via isocyanate, may be considered as a new physiological route of MQA formation.

Local Melatoninergic System as the Protector of Skin Integrity

“…AFMK is then further metabolized by arylamine formamidase to become N 1 -acetyl-5-methoxykynuramine (AMK) [61]. AMK can react with carbamoyl phosphate, H 2 O 2 , and Cu 2+ to form MQA ( N [2-(6-methoxyquinazolin-4-yl] [67]. AMK can also (theoretically) react with either NO + , NO, or HNO to form AAMC (3-acetyamidomethyl-6-methoxycinnolinone) [68].…”

Melatonin‐mediated Bim up‐regulation and cyclooxygenase‐2 (COX‐2) down‐regulation enhances tunicamycin‐induced apoptosis in MDA‐MB‐231 cells

“…Melatonin, an indolamine derived from the amino acid tryptophan, controls important physiological functions including seasonal reproduction and circadian rhythms [1,2]. Numerous investigations have documented that melatonin may be an attractive candidate as an antitumor agent or for combined therapy because of its endogenous free radical scavenging activity and oncostatic properties [3][4][5][6][7][8][9]. Many studies have related its oncostatic and antitumor features with its ability to induce apoptosis and inhibit angiogenesis and metastasis [10][11][12][13][14][15].…”

Melatonin Metabolism in the Central Nervous System

“…Among the products formed by interaction with reactive nitrogen species, three main products were obtained in chemical systems, N 1 -acetyl-5-methoxy-3-nitrokynuramine (AMNK, 3-nitro-AMK), N- [2-(6-methoxyquinazoline-4-yl)ethyl] acetamide (MQA) and 3-acetamidomethyl-6-methoxycinnolinone (AMMC) [36,68] (Fig. 4).…”