In Silico Study of the Interaction Between Human 5-HT2C Receptor and Antidepressant Drug Candidates
Resumo
Depression is a major public health concern affecting 300 million people worldwide, according to WHO. The mechanism of depression is presumed to be related to the role of serotonin (5-hydroxytryptamine - 5-HT) and its receptors in the central nervous system. In this work a human 5-HT2C receptor model was created by homology modeling, and molecular docking studies were performed with the ligands fulvic acid, paroxetine, citalopram, and serotonin itself. Fulvic acid had similar affinity parameters to paroxetine and s-citalopram, which are widely used drugs for the treatment of psychiatric disorders such as depression and anxiety.
Referências
Berman, H. M. (1 jan 2000). The Protein Data Bank. Nucleic Acids Research, v. 28, n.1, p. 235–242.
Bhavsar, S. K., Thaker, A. M. and Malik, J. K. (2016). Shilajit. Nutraceuticals. Elsevier. p. 707–716.
Borroto-Escuela, D., Narváez, M., Ambrogini, P., et al. (3 jun 2018). Receptor–Receptor Interactions in Multiple 5-HT1A Heteroreceptor Complexes in Raphe-Hippocampal 5-HT Transmission and Their Relevance for Depression and Its Treatment. Molecules, v. 23, n. 6, p. 1341.
Chien, S.-J., Chen, T.-C., Kuo, H.-C., Chen, C.-N. and Chang, S.-F. (dec 2015). Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes. BMC Complementary and Alternative Medicine, v. 15, n. 1.
Davis, B. A., Nagarajan, A., Forrest, L. R. and Singh, S. K. (1 apr 2016). Mechanism of Paroxetine (Paxil) Inhibition of the Serotonin Transporter. Scientific Reports, v. 6.
Eswar, N., Webb, B., Marti-Renom, M. A., et al. (sep 2006). Comparative Protein Structure Modeling Using Modeller. Current Protocols in Bioinformatics, v. 15, n. 1, p. 5.6.1-5.6.30.
Grandjean, J., Corcoba, A., Kahn, M. C., et al. (dec 2019). A brain-wide functional map of the serotonergic responses to acute stress and fluoxetine. Nature Communications, v. 10, n. 1.
Kim, S., Chen, J., Cheng, T., et al. (8 jan 2019). PubChem 2019 update: improved access to chemical data. Nucleic Acids Research, v. 47, n. D1, p. D1102–D1109.
Marek, G. J. (2017). Developing Serotonergic Antidepressants Acting on More Than the Serotonin Transporter. In: Handler, N.; Buschmann, H.[Eds.]. . Methods and Principles in Medicinal Chemistry. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA. p. 335–367.
Matthäus, F., Haddjeri, N., Sánchez, C., et al. (2016). The allosteric citalopram binding site differentially interferes with neuronal firing rate and SERT trafficking in serotonergic neurons. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology, v. 26, n. 11, p. 1806–1817.
Morris, G. M., Huey, R., Lindstrom, W., et al. (dec 2009). AutoDock4 and AutoDockTools4: Automated Docking with Selective Receptor Flexibility. Journal of computational chemistry, v. 30, n. 16, p. 2785–2791.
Palacios, J. M. (15 aug 2016). Serotonin receptors in brain revisited. Brain Research, v. 1645, p. 46–49.
Pettersen, E. F., Goddard, T. D., Huang, C. C., et al. (oct 2004). UCSF Chimera?A visualization system for exploratory research and analysis. Journal of Computational Chemistry, v. 25, n. 13, p. 1605–1612.
Plácido, A., Coelho, A., Abreu Nascimento, L., et al. (jul 2017). Cry1A(b)16 toxin from Bacillus thuringiensis : Theoretical refinement of three-dimensional structure and prediction of peptides as molecular markers for detection of genetically modified organisms: Cry1A(b)16 Structure and Prediction of Peptides for Detection of GMO. Proteins: Structure, Function, and Bioinformatics, v. 85, n. 7, p. 1248–1257.
Qin, Y., Zhang, M., Dai, W., et al. (sep 2019). Antidiarrhoeal mechanism study of fulvic acids based on molecular weight fractionation. Fitoterapia, v. 137, p. 104270.
Saleh, F. Y., Ong, W. A. and Chang, D. Y. (15 dec 1989). Structural features of aquatic fulvic acids. Analytical and preparative reversed-phase high-performance liquid chromatography separation with photodiode array detection. Analytical Chemistry, v. 61, n. 24, p. 2792–2800.
Sherry, L., Jose, A., Murray, C., et al. (2012). Carbohydrate Derived Fulvic Acid: An in vitro Investigation of a Novel Membrane Active Antiseptic Agent Against Candida albicans Biofilms. Frontiers in Microbiology, v. 3.
Thurman, E. M. and Malcolm, R. L. (apr 1981). Preparative isolation of aquatic humic substances. Environmental Science & Technology, v. 15, n. 4, p. 463–466.
Tohda, M. (2014). Serotonin 2C Receptor as a Superhero: Diversities and Talents in the RNA Universe for Editing, Variant, Small RNA and Other Expected Functional RNAs. Journal of Pharmacological Sciences, v. 126, n. 4, p. 321–328.
Trott, O. and Olson, A. J. (30 jan 2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, v. 31, n. 2, p. 455–461.
Verma, S., Singh, A. and Mishra, A. (jan 2013). The effect of fulvic acid on pre‐ and postaggregation state of Aβ17–42: Molecular dynamics simulation studies. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, v. 1834, n. 1, p. 24–33.
Vucskits, A. V., Hullár, I., Bersényi, A., et al. (dec 2010). Effect of fulvic and humic acids on performance, immune response and thyroid function in rats: Effects of fulvic acid and humic acid in rats. Journal of Animal Physiology and Animal Nutrition, v. 94, n. 6, p. 721–728.
WHO (22 mar 2018). Depression. https://www.who.int/news-room/fact-sheets/detail/depression, [accessed on Jul 30].
Yohn, C. N., Gergues, M. M. and Samuels, B. A. (dec 2017). The role of 5-HT receptors in depression. Molecular Brain, v. 10, n. 1.
Zhao, Y., Paderu, P., Delmas, G., et al. (oct 2015). Carbohydrate-derived fulvic acid is a highly promising topical agent to enhance healing of wounds infected with drug-resistant pathogens. The Journal of Trauma and Acute Care Surgery, v. 79, n. 4 Suppl 2, p. S121-129.
Bhavsar, S. K., Thaker, A. M. and Malik, J. K. (2016). Shilajit. Nutraceuticals. Elsevier. p. 707–716.
Borroto-Escuela, D., Narváez, M., Ambrogini, P., et al. (3 jun 2018). Receptor–Receptor Interactions in Multiple 5-HT1A Heteroreceptor Complexes in Raphe-Hippocampal 5-HT Transmission and Their Relevance for Depression and Its Treatment. Molecules, v. 23, n. 6, p. 1341.
Chien, S.-J., Chen, T.-C., Kuo, H.-C., Chen, C.-N. and Chang, S.-F. (dec 2015). Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes. BMC Complementary and Alternative Medicine, v. 15, n. 1.
Davis, B. A., Nagarajan, A., Forrest, L. R. and Singh, S. K. (1 apr 2016). Mechanism of Paroxetine (Paxil) Inhibition of the Serotonin Transporter. Scientific Reports, v. 6.
Eswar, N., Webb, B., Marti-Renom, M. A., et al. (sep 2006). Comparative Protein Structure Modeling Using Modeller. Current Protocols in Bioinformatics, v. 15, n. 1, p. 5.6.1-5.6.30.
Grandjean, J., Corcoba, A., Kahn, M. C., et al. (dec 2019). A brain-wide functional map of the serotonergic responses to acute stress and fluoxetine. Nature Communications, v. 10, n. 1.
Kim, S., Chen, J., Cheng, T., et al. (8 jan 2019). PubChem 2019 update: improved access to chemical data. Nucleic Acids Research, v. 47, n. D1, p. D1102–D1109.
Marek, G. J. (2017). Developing Serotonergic Antidepressants Acting on More Than the Serotonin Transporter. In: Handler, N.; Buschmann, H.[Eds.]. . Methods and Principles in Medicinal Chemistry. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA. p. 335–367.
Matthäus, F., Haddjeri, N., Sánchez, C., et al. (2016). The allosteric citalopram binding site differentially interferes with neuronal firing rate and SERT trafficking in serotonergic neurons. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology, v. 26, n. 11, p. 1806–1817.
Morris, G. M., Huey, R., Lindstrom, W., et al. (dec 2009). AutoDock4 and AutoDockTools4: Automated Docking with Selective Receptor Flexibility. Journal of computational chemistry, v. 30, n. 16, p. 2785–2791.
Palacios, J. M. (15 aug 2016). Serotonin receptors in brain revisited. Brain Research, v. 1645, p. 46–49.
Pettersen, E. F., Goddard, T. D., Huang, C. C., et al. (oct 2004). UCSF Chimera?A visualization system for exploratory research and analysis. Journal of Computational Chemistry, v. 25, n. 13, p. 1605–1612.
Plácido, A., Coelho, A., Abreu Nascimento, L., et al. (jul 2017). Cry1A(b)16 toxin from Bacillus thuringiensis : Theoretical refinement of three-dimensional structure and prediction of peptides as molecular markers for detection of genetically modified organisms: Cry1A(b)16 Structure and Prediction of Peptides for Detection of GMO. Proteins: Structure, Function, and Bioinformatics, v. 85, n. 7, p. 1248–1257.
Qin, Y., Zhang, M., Dai, W., et al. (sep 2019). Antidiarrhoeal mechanism study of fulvic acids based on molecular weight fractionation. Fitoterapia, v. 137, p. 104270.
Saleh, F. Y., Ong, W. A. and Chang, D. Y. (15 dec 1989). Structural features of aquatic fulvic acids. Analytical and preparative reversed-phase high-performance liquid chromatography separation with photodiode array detection. Analytical Chemistry, v. 61, n. 24, p. 2792–2800.
Sherry, L., Jose, A., Murray, C., et al. (2012). Carbohydrate Derived Fulvic Acid: An in vitro Investigation of a Novel Membrane Active Antiseptic Agent Against Candida albicans Biofilms. Frontiers in Microbiology, v. 3.
Thurman, E. M. and Malcolm, R. L. (apr 1981). Preparative isolation of aquatic humic substances. Environmental Science & Technology, v. 15, n. 4, p. 463–466.
Tohda, M. (2014). Serotonin 2C Receptor as a Superhero: Diversities and Talents in the RNA Universe for Editing, Variant, Small RNA and Other Expected Functional RNAs. Journal of Pharmacological Sciences, v. 126, n. 4, p. 321–328.
Trott, O. and Olson, A. J. (30 jan 2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, v. 31, n. 2, p. 455–461.
Verma, S., Singh, A. and Mishra, A. (jan 2013). The effect of fulvic acid on pre‐ and postaggregation state of Aβ17–42: Molecular dynamics simulation studies. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, v. 1834, n. 1, p. 24–33.
Vucskits, A. V., Hullár, I., Bersényi, A., et al. (dec 2010). Effect of fulvic and humic acids on performance, immune response and thyroid function in rats: Effects of fulvic acid and humic acid in rats. Journal of Animal Physiology and Animal Nutrition, v. 94, n. 6, p. 721–728.
WHO (22 mar 2018). Depression. https://www.who.int/news-room/fact-sheets/detail/depression, [accessed on Jul 30].
Yohn, C. N., Gergues, M. M. and Samuels, B. A. (dec 2017). The role of 5-HT receptors in depression. Molecular Brain, v. 10, n. 1.
Zhao, Y., Paderu, P., Delmas, G., et al. (oct 2015). Carbohydrate-derived fulvic acid is a highly promising topical agent to enhance healing of wounds infected with drug-resistant pathogens. The Journal of Trauma and Acute Care Surgery, v. 79, n. 4 Suppl 2, p. S121-129.
Publicado
26/12/2019
Como Citar
BARROS, Romulo; COSTA, Jhonatan ; PEREIRA, Wildrimak ; MENDES, Diego; CARDOSO JÚNIOR, Fábio; RAMOS, Ricardo .
In Silico Study of the Interaction Between Human 5-HT2C Receptor and Antidepressant Drug Candidates. In: ESCOLA REGIONAL DE COMPUTAÇÃO APLICADA À SAÚDE (ERCAS), 7. , 2019, Teresina.
Anais [...].
Porto Alegre: Sociedade Brasileira de Computação,
2019
.
p. 25-30.
