Hydroxyl radical scavenging activity of melatonin and its related indolamines

Abstract

The hydroxyl radical (•OH) scavenging activities of Melatonin, an endogenously produced neurohormone and its related indolamines like N-acetyl tryptophan (NAT) and N-acetyl serotonin (NAS) have been investigated using density functional theory. The mechanism involves 4 steps: initial radical addition to position-3 of the indole ring, keto-amine to enol-imine tautomerization, cyclisation, and finally, addition of a second •OH leading to a cyclic end product. Incorporation of an explicit water molecule in tautomerization step leads to a significant reduction in the barrier of this step, so that the subsequent cyclisation step becomes rate-limiting. In agreement with the very high reactivity of •OH, the initial and final addition of •OH to indolamine are found to be barrierless. Radical adduct formed in the initial step was found to be very stable due to the extensive conjugation present in the substrate. Our calculations show that melatonin is the most effective radical scavenger among the three molecules chosen. NAS was found to exhibit antiradical property comparable to that of melatonin. In contrast to the general observation of reduced antioxidant activity of tryptophan, a non-natural derivative of tryptophan used here (NAT) is found to have good radical scavenging activity. This work further implies that non-natural derivatives of indolamines might as well be useful in the detoxification of free radicals as they exhibit almost comparable antioxidant efficiency as that of melatonin.