Reactions of melatonin and related indoles with free radicals: a computational study.
Melatonin is being increasingly promoted as a therapeutic agent for the treatment of jet lag and insomnia and has been recently suggested to act as an efficient free-radical scavenger. In the present work, its mechanisms of action for scavenging hydroxyl radicals have been investigated using semiempirical AM1 and density functional theory (DFT) computational tools. Two different reactions were proposed as follows: one involving the abstraction of an indolic hydrogen to yield a neutral radical and another involving the addition of the hydroxyl radical to the indolic moiety. Our results show that, from a thermodynamical standpoint, melatonin may directly scavenge hydroxyl radicals both in vacuum and in aqueous solution. The structural requirements for free-radical-trapping ability have been examined comparing melatonin with related indoles. Computational data suggest that 5-methoxy and N-acetyl groups of melatonin do not significantly affect its thermodynamical capacity of free-radical trapping. The present results support experimental data on the potential of melatonin as a physiological or pharmacological antioxidant agent.
Turjanski
A G
AG
Departamento de Química Inorgánica, Analítica y Química-Física and INQUIMAE, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Rosenstein
R E
RE
Estrin
D A
DA
D003198:Computer Simulation; D016166:Free Radical Scavengers / Q000737:chemistry*; D017665:Hydroxyl Radical / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D008550:Melatonin / Q000737:chemistry*; D008954:Models, Biological; D011789:Quantum Theory; D012996:Solutions; D013481:Superoxides / Q000737:chemistry*; D013816:Thermodynamics; D014618:Vacuum; D014867:Water
D016166:Free Radical Scavengers; D007211:Indoles; D012996:Solutions; D014867:Water; D013481:Superoxides; D017665:Hydroxyl Radical; D008550:Melatonin