Artículo

Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

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-tapping 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.

Registro:

Documento: Artículo
Título:Reactions of melatonin and related indoles with free radicals: A computational study
Autor:Turjanski, A.G.; Rosenstein, R.E.; Estrin, D.A.
Filiación:Depto. Quim. Inorg., Analitica y Q., Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón II, 1428 Buenos Aires, Argentina
Departamento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 7 P Buenos Aires, Argentina
Palabras clave:antioxidant; free radical; indole derivative; melatonin; antioxidant activity; aqueous solution; article; hormone action; insomnia; jet lag; scavenging system; thermodynamics; Computer Simulation; Free Radical Scavengers; Hydroxyl Radical; Indoles; Melatonin; Models, Biological; Quantum Theory; Solutions; Superoxides; Thermodynamics; Vacuum; Water
Año:1998
Volumen:41
Número:19
Página de inicio:3684
Página de fin:3689
DOI: http://dx.doi.org/10.1021/jm980117m
Título revista:Journal of Medicinal Chemistry
Título revista abreviado:J. Med. Chem.
ISSN:00222623
CODEN:JMCMA
CAS:Free Radical Scavengers; Hydroxyl Radical, 3352-57-6; Indoles; Melatonin, 73-31-4; Solutions; Superoxides, 11062-77-4; Water, 7732-18-5
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00222623_v41_n19_p3684_Turjanski

Referencias:

  • Casone, V.M., Melatonin and Suprachiasmatic Nucleus Function (1991) Suprachiasmatic Nucleus, pp. 309-323. , Klein, D. C., Moore, R. Y., Reppert, S. M., Eds.; Oxford University Press: Oxford
  • Reiter, R.J., Functional Pleiotropy of the Neurohormone Melatonin: Antioxidant Protection and Neuroendocrine Regulation (1995) Front. Neuroendocrinol., 16, pp. 383-415
  • Reiter, R.J., Ortiz, G.G., Gaia Monti, M., Carneiro, R.C., Cellular and Molecular Actions of Melatonin as an Antioxidant (1997) Therapeutic Potential of Melatonin, 23, pp. 81-88. , Front Horm Res Maetroni G., J. M., Conti, A., Reiter, R. J., Eds.; Karger: Basel
  • Barlow-Walden, L.R., Reiter, R.J., Abe, M., Pablos, M., Menendez-Pelaéz, A., Chen, L.D., Poeggeler, B., Melatonin Stimulates Brain Glutathione Peroxidase Activity (1995) Neurochem. Int., 26, pp. 497-502
  • Antolin, I., Rodriguez, C., Sainz, R.M., Mayo, J.C., Uria, H., Koteer, M.L., Rodriguez-Colunga, M.J., Menendez-Pelaez, A., Neurohormone Melatonin Prevents Cell Damage: Effect on Gene Expression of Antioxidative Enzymes (1996) FASEB J., 10, pp. 882-890
  • Tan, D.X., Poeggeler, B., Reiter, R.J., Chen, L.D., Chen, S., Manchester, L.C., Barlow-Walden, L.R., The Pineal Hormone Melatonin Inhibits DNA Adduct Formation Induced by the Chemical Carcinogen Safrole In Vivo (1993) Cancer Lett., 70, pp. 65-71
  • Sewerynek, E., Melchiorri, D., Reiter, R.J., Ortiz, G.G., Lewinsy, A., Lipopolysaccharide-induced Hepatotoxicity is Inhibited by the Antioxidant Melatonin (1995) Eur. J. Pharmacol., 293, pp. 327-334
  • Sewerynek, E., Abe, M., Reiter, R.J., Barlow-Walden, L.R., Chen, L.D., McCabe, T.J., Roman, L.J., Diaz-Lopez, B., Melatonin Administration Prevents Lipopolysaccharide Induced Oxidative Damage in Phenobarbital-treated Animals (1995) J. Cell Biochem., 58, p. 436
  • Melchiorri, D., Reiter, R.J., Attia, A.M., Kara, M., Burgos, A., Nistico, G., Potent Protective Effect of Melatonin on In Vivo Paraquat-induced Oxidative Damage in Rats (1995) Life Sci., 56, p. 83
  • Reiter, R.J., Poeggeler, B., Tan, D., Chen, L., Manchester, L., Guerrero, J.M., Antioxidant Capacity of Melatonin: A Novel Action Not Requiring a Receptor (1993) Neuroendocrinol. Lett., 15, pp. 103-116
  • Hardeland, R., Reiter, R.J., Poeggeler, B., Tan, S.D., The Significance of the Metabolism of the Neurohormone Melatonin: Antioxidative Protection and Formation of Bioactive Substance (1993) Neurosci. Biobehav. Rev., 17, pp. 347-357
  • Dewar, M.J.S., Zoebisch, E.G., Healy, E.F., Stewart, J.J.P., AM1: A New General Purpose Quantum Mechanical Molecular Model (1985) J. Am. Chem. Soc., 107, pp. 3902-3909
  • Hirst, D.M., (1990) A Computational Approach to Quantum Chemistry, , Blackwell Scientific Publications: Oxford
  • Cramer, C.J., Truhlar, D.G., Correlation and Solvation Effects on Heterocyclic Equilibria in Aqueous Solution (1993) J. Am. Chem. Soc., 115, pp. 8810-8817
  • Estrin, D.A., Corongiu, G., Clementi, E., Structure and Dynamics of Molecular Systems Using Density Functional Theory (1993) METECC, Methods and Techniques in Computational Chemistry, pp. 541-567. , Clementi, E., Ed.; Stef: Cagliari
  • Estrin, D.A., Paglieri, L., Corongiu, G., A Density Functional Study of Tautomerism of Uracil and Cytosine (1994) J. Phys. Chem., 98, pp. 5653-5660
  • Parr, R.G., Yang, W., (1990) Density Functional Theory of Atoms and Molecules, , Oxford University Press: New York
  • Perdew, P.W., Density-Functional Approximation for the Correlation Energy of the Inhomogeneous Electron Gas (1986) Phys. Rev., B33, p. 8800
  • (1986) Phys. Rev., B34, p. 7406. , erratum
  • Becke, A.D., Density-Functional Exchange-Energy Approximation with Correct Asymptotic Behaviour (1988) Phys. Rev., A38, p. 3098
  • Godbout, N., Salahub, D.R., Andzelm, J., Wimmer, E., Optimization of Gaussian Type Basis Sets for Local Spin Density Functional Calculations. Part. I Boron through Neon, Optimization, Technique and Validation (1992) Can. J. Chem., 70, pp. 560-572
  • Hill, T.L., (1986) An Introduction to Statistical Thermodynamics, , Dover Publications: New York
  • Shida, C.S., Castrucci, M.T., Lamy-Freund, M.T., High Melatonin Solubility in Aqueous Medium (1994) J. Pineal Res., 16, pp. 198-201
  • Cramer, C.J., Truhlar, D.G., Continuum Solvation Models (1995) Reviews in Computational Chemistry, 6. , Lipkowitz, K. B., Boyd D. B., Eds.; VCH: New York, Chapter 1
  • Harris, D., Loew, G., Comparative Study of Free Energies of Solvation of Phenylimidazole Inhibitors of Cytochrome P450cam by Free Energy Simulation. Amsol, and Poisson Boltzmann Methods (1996) J. Comput. Chem., 17, pp. 273-288
  • Iddon, B., Phillips, G.O., Robbins, K.E., Davies, J.V., Radiation Chemistry of Aqueous Solutions of Indole and Its Derivatives (1971) J. Chem. Soc. B, pp. 1887-1892
  • Perez-Reyes, E., Mason, R.R., Characterization of the Structure and Reactions of Free Radicals from Serotonin and Related Indoles (1981) J. Biol. Chem., 10, pp. 2427-2432
  • Tabor, M.W., Coats, E., Sainsbury, M., Shertzer, H.G., Antioxidation Potential of Indoles Compounds-Structure Activity Studies (1991) Biological Reactive Intermediates, 4, pp. 833-836. , Witmer, C. M., Jollow, D. D., Kalf, G. F., Kocsis, J. J., Sipes, I. G., Eds.; Plenum Press: New York
  • Simic, M., Jovanovic, S.V., Mechanism of Inactivation of Oxygen Radicals by Dietary Antioxidants and their Models (1990) Basic Life Sci., 52, pp. 127-137
  • Jovanovic, S.V., Simic, M.G., Tryptophan Metabolites as Antioxidants (1985) Life Chem. Rep., 3, pp. 124-130
  • Wrona, M.Z., Yang, Z., McAdams, M., Oçonnor-Coates, S., Dryhurst, G., Hydroxyl Radical-Mediated Oxidation of Serotonin: Potential Insights into the Neurotoxicity of Methamphetamine (1995) J. Neurochem., 64, pp. 1390-1400
  • Matuszak, Z., Reszka, K.J., Chignell, C.F., Reaction of Melatonin and Related Indoles with Hydroxyl Radicals: EPR and Spin Trapping Investigations (1997) Free Radical Biol. Med., 3, pp. 367-372
  • Menendez-Pelaez, A., Poeggeler, B., Reiter, R.J., Barlow-Walden, L.R., Pablos, M.I., Tan, D.X., Nuclear Localization of Melatonin in Different Mammalian Tissues. Immunocytochemical and Radioimmunoassay Evidence (1993) J. Cell Biochem., 53, pp. 372-382
  • Faillace, M.P., Cutrera, R., Keller Sarmiento, M.I., Rosenstein, R.E., Evidence for Local Synthesis of Melatonin in Golden Hamster Retina (1995) Neuroreport, 6, pp. 2093-2095
  • Marshall, K.A., Reiter, R.J., Poeggeler, B., Aruoma, O.I., Halliwell, B., Evaluation of the Antioxidant Activity of Melatonin In Vitro (1996) Free Radical Biol. Med., 3, pp. 307-315

Citas:

---------- APA ----------
Turjanski, A.G., Rosenstein, R.E. & Estrin, D.A. (1998) . Reactions of melatonin and related indoles with free radicals: A computational study. Journal of Medicinal Chemistry, 41(19), 3684-3689.
http://dx.doi.org/10.1021/jm980117m
---------- CHICAGO ----------
Turjanski, A.G., Rosenstein, R.E., Estrin, D.A. "Reactions of melatonin and related indoles with free radicals: A computational study" . Journal of Medicinal Chemistry 41, no. 19 (1998) : 3684-3689.
http://dx.doi.org/10.1021/jm980117m
---------- MLA ----------
Turjanski, A.G., Rosenstein, R.E., Estrin, D.A. "Reactions of melatonin and related indoles with free radicals: A computational study" . Journal of Medicinal Chemistry, vol. 41, no. 19, 1998, pp. 3684-3689.
http://dx.doi.org/10.1021/jm980117m
---------- VANCOUVER ----------
Turjanski, A.G., Rosenstein, R.E., Estrin, D.A. Reactions of melatonin and related indoles with free radicals: A computational study. J. Med. Chem. 1998;41(19):3684-3689.
http://dx.doi.org/10.1021/jm980117m