Melatonin, N-Acetyl-5-methoxytryptamine

Melatonin is a neurohormone, first isolated in 1958 from bovine pineal tissue, has a central role in the regulation of daily rhythms and seasonal cycles in vertebrates. Its potential usefulness to a number of therapeutic areas such as those related to the desynchronization of biological rhythms, such as jet-lag, disturbed sleep-wake cycles, seasonal disorders and depression are known. Melatonin may also play a role in the cardiovascular system. This is supported by recent findings which show that 2-[125I] iodomelatonin-binding sites are localized in both the caudal and cerebral arteries of the rat. In addition, melatonin binding has been reported at many other sites including the retina (probably related to resynchronization role) and peripheral tissues such as the spleen (related to a role immune system), gastrointestinal tract, blood platelets and the harderian gland. Furthermore antioxidant properties of melatonin have recently been proposed. Although the effects of melatonin in oncogenesis are unclear; majority of the studies conclude that the hormone has a protective role in the modulation of cancer or cancerous cells. Melatonin may also play a role in brain function, but the mechanisms underlying such functions are yet not known.

Despite its potential involvement in the regulation in many possible physiological processes, two problems limit its therapeutic use at present. The first is, its very short biological half-life (15-30 min), due to its rapid metabolism to 6-hydroxymelatonin and N-acetylkynurenamines, and second is the lack of selectivity of melatonin at target sites. It is thought that the development of novel analogues may provide a strategic approach to overcome both of these limitations. Therefore, we have synthesized novel melatonin derivatives and investigate their antioxidant capacities.