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

The reactions of N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK) with center dot OH, center dot OOH, and center dot 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 center dot OH at diffusion-limited rates, regardless of the polarity of the environment, which supports their excellent center dot OH radical scavenging activity. Both compounds were found to be also very efficient for scavenging center dot OOCCl3, but rather ineffective for scavenging center dot 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 center dot OOH and center dot OOCCl3 scavenger than AMK, while AMK is predicted to be slightly better than melatonin for scavenging center dot 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.