In Silico Repositioning Strategies of Theobromine and Caffeine for Psychiatric and Neurological Disorders
Keywords:
Brewed coffee, dark chocolate, neurological disorders, psychiatric disordersAbstract
Psychiatric and neurological disorders (PNDs) have correlated diseases and represent a burden on public health. Several drugs are reported to repurpose PNDs therapy. Drugs with antidepressants, anxiolytics, stimulants, antipsychotics, and mood stabilizers are classified for PNDs treatments. Due to the high cost of PNDs therapy and developing novel drugs, this study focused on identifying the theobromine and caffeine for PNDs treatments. Theobromine and caffeine as main compounds of brewed coffee and chocolate were downloaded their 3D structure from the PubChem compound database. Several targetted PNDs proteins involved Adenosine 1 receptor, adenosine 2 receptor, serotonin receptor, GABA receptor, and Acetylcholinesterase were downloaded from protein data bank and predicted their binding cavities by Molegro virtual docker 5. Ligands and proteins were docked and visualized to investigate the inhibition sites. Caffeine and theobromine showed interaction with adenosine 1 receptor and adenosine 2 receptor in adenosine sites, since there were depicting similar structure. Caffeine and theobromine also performed same active sites with serotonin receptor 4 and GABA receptor, indicating a potential activity as serotonin and GABA molecules. Acetylcholinesterase was inhibited by caffeine and theobromine at the catalytic residues. In summary, caffeine and theobromine performed a potential neuroprotection effect for PNDs therapeutics.
References
Agarwal, V., Agarwal, S., Kaur, R., Pancham, P., Kaur, H., Bhardwaj, S., & Singh, M. 2020. In silico Validation and Development of Chlorogenic Acid (CGA) Loaded Polymeric Nanoparticle for Targeting Neurodegenerative Disorders. Journal of Biomaterials and Nanobiotechnology, 11(04), 279–303. https://doi.org/10.4236/jbnb.2020.114018
Auti, S. T., & Kulkarni, Y. A. 2019. Neuroprotective effect of cardamom oil against aluminum induced neurotoxicity in rats. Frontiers in Neurology, 10(APR), 1–17. https://doi.org/10.3389/fneur.2019.00399
Bare, Y., Krisnamurti, G. C., Elizabeth, A., Rachmad, Y. T., Sari, D. R. T., & Gabrella Lorenza, M. R. W. 2019. The potential role of caffeic acid in coffee as cyclooxygenase-2 (COX-2) inhibitor: In silico study. Biointerface Research in Applied Chemistry, 9(5). https://doi.org/10.33263/BRIAC95.424427
Bare, Yohanes, Kuki, A. D., Daeng Tiring, S. S. N., Rophi, A. H., Krisnamurti, G. C., & Sari, D. R. T. 2020. In Silico Study: Prediction the Potential of Caffeic Acid As ACE inhibitor. El-Hayah, 7(3), 94–98. https://doi.org/10.18860/elha.v7i3.10053
Bare, Yohanes, Sari, D. R. T., Rachmad, Y. T., Krisnamurti, G. C., & Elizabeth, A. 2019. In Silico Insight the Prediction of Chlorogenic Acid in Coffee through Cyclooxygenase-2 (COX2) Interaction. Biogenesis: Jurnal Ilmiah Biologi, 7(2), 100–105. https://doi.org/10.24252/bio.v7i2.9847
Bitencourt-Ferreira, G., & de Azevedo, W. F. J. 2019. Molegro Virtual Docker for Docking. Methods in Molecular Biology (Clifton, N.J.), 2053, 149–167. https://doi.org/10.1007/978-1-4939-9752-7_10
Camandola, S., Plick, N., & Mattson, M. P. 2019. Impact of Coffee and Cacao Purine Metabolites on Neuroplasticity and Neurodegenerative Disease. Neurochemical Research, 44(1), 214–227. https://doi.org/10.1007/s11064-018-2492-0
Cheng, R. K. Y., Segala, E., Robertson, N., Deflorian, F., Doré, A. S., Errey, J. C., … Cooke, R. M. 2017. Structures of Human A1 and A2A Adenosine Receptors with Xanthines Reveal Determinants of Selectivity. Structure, 25(8), 1275-1285.e4. https://doi.org/10.1016/j.str.2017.06.012
Cheung, J., Rudolph, M. J., Burshteyn, F., Cassidy, M. S., Gary, E. N., Love, J., … Height, J. J. 2012. Structures of human acetylcholinesterase in complex with pharmacologically important ligands. Journal of Medicinal Chemistry, 55(22), 10282–10286. https://doi.org/10.1021/jm300871x
De Pinho, L. G., Lopes, M. J., Correia, T., Sampaio, F., Do Arco, H. R., Mendes, A., … Fonseca, C. 2021. Patient-centered care for patients with depression or anxiety disorder: An integrative review. Journal of Personalized Medicine, 11(8). https://doi.org/10.3390/jpm11080776
Jaakola, V. P., Griffith, M. T., Hanson, M. A., Cherezov, V., Chien, E. Y. T., Lane, J. R., … Stevens, R. C. 2008. The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist. Science, 322(5905), 1211–1217. https://doi.org/10.1126/science.1164772
Johnston, G. A. R. 2013. Advantages of an antagonist: Bicuculline and other GABA antagonists. British Journal of Pharmacology, 169(2), 328–336. https://doi.org/10.1111/bph.12127
Kolahdouzan, M., & Hamadeh, M. J. 2017. The neuroprotective effects of caffeine in neurodegenerative diseases. CNS Neuroscience and Therapeutics, 23(4), 272–290. https://doi.org/10.1111/cns.12684
Kwon, S. H., Lee, H. K., Kim, J. A., Hong, S. I., Kim, H. C., Jo, T. H., … Jang, C. G. 2010. Neuroprotective effects of chlorogenic acid on scopolamine-induced amnesia via anti-acetylcholinesterase and anti-oxidative activities in mice. European Journal of Pharmacology, 649(1–3), 210–217. https://doi.org/10.1016/j.ejphar.2010.09.001
Liu, Y. H., Lee, C. J., Chen, L. C., Lee, T. L., Hsieh, Y. Y., Han, C. H., … Hou, W. C. 2020. Acetylcholinesterase inhibitory activity and neuroprotection: In vitro, molecular docking, and improved learning and memory functions of demethylcurcumin in scopolamine-induced amnesia ICR mice. Food and Function, 11(3), 2328–2338. https://doi.org/10.1039/c9fo02339a
Lohning, A. E., Marx, W., & Isenring, L. 2016. In silico investigation into the interactions between murine 5-HT3 receptor and the principle active compounds of ginger (Zingiber officinale). Journal of Molecular Graphics and Modelling, 70, 315–327. https://doi.org/10.1016/j.jmgm.2016.10.008
Meng, S., Cao, J., Feng, Q., Peng, J., & Hu, Y. 2013. Roles of chlorogenic acid on regulating glucose and lipids metabolism: A review. Evidence-Based Complementary and Alternative Medicine, 2013. https://doi.org/10.1155/2013/801457
Mondal, P., Gupta, V., Das, G., Pradhan, K., Khan, J., Gharai, P. K., & Ghosh, S. 2018. Peptide-Based Acetylcholinesterase Inhibitor Crosses the Blood-Brain Barrier and Promotes Neuroprotection. ACS Chemical Neuroscience, 9(11), 2838–2848. https://doi.org/10.1021/acschemneuro.8b00253
Motamayor, J. C., Mockaitis, K., Schmutz, J., Haiminen, N., Livingstone, D., Cornejo, O., … Kuhn, D. N. 2013. The genome sequence of the most widely cultivated cacao type and its use to identify candidate genes regulating pod color. Genome Biology, 14(6), r53. https://doi.org/10.1186/gb-2013-14-6-r53
Pires, D. E. V., Blundell, T. L., & Ascher, D. B. 2015. pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of Medicinal Chemistry, 58(9), 4066–4072. https://doi.org/10.1021/acs.jmedchem.5b00104
Putri, S. P., Irifune, T., Yusianto, & Fukusaki, E. 2019. GC/MS based metabolite profiling of Indonesian specialty coffee from different species and geographical origin. Metabolomics, 15(10), 1–11. https://doi.org/10.1007/s11306-019-1591-5
Rath, S. N., Jena, L., Bhuyan, R., Mahanandia, N. C., & Patri, M. 2021. In silico discovery and evaluation of phytochemicals binding mechanism against human Catechol-O-methyltransferase as a putative bioenhancer of L-DOPA therapy in parkinson disease. Genomics and Informatics, 19(1), 1–13. https://doi.org/10.5808/gi.20061
Remya, C., Dileep, K. V., Koti Reddy, E., Mantosh, K., Lakshmi, K., Sarah Jacob, R., … Omkumar, R. V. 2021. Neuroprotective derivatives of tacrine that target NMDA receptor and acetyl cholinesterase – Design, synthesis and biological evaluation. Computational and Structural Biotechnology Journal, 19, 4517–4537. https://doi.org/10.1016/j.csbj.2021.07.041
Sakhuja, Rajeev; Kondabolu, Krishnakanth; Cordova-Sintjago, Tania; Travers, Sean; Vincek, Adam S; Kim, Myong Sang; Abboud, Khalil A.; Fang, Lijuan; Sun, Zhuming; Canal, Clinton E.; Booth, R. G. 2015. Novel 4-Substituted-N,N-dimethyltetrahydronaphthalen-2- amines: Synthesis, Affinity, and In Silico Docking Studies at Serotonin 5-HT2-type and Histamine H1 G Protein-Coupled Receptors. Bioorg Med Chem, 23(7), 1588–1600. https://doi.org/10.1016/j.bmc.2015.01.060
Santomauro, D. F., Mantilla Herrera, A. M., Shadid, J., Zheng, P., Ashbaugh, C., Pigott, D. M., … Ferrari, A. J. 2021. Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic. The Lancet, 398(10312), 1700–1712. https://doi.org/10.1016/s0140-6736(21)02143-7
Sari, Dewi Ratih Tirto; Krisnamurti, G. C. 2021. 1-dehydrogingerdione , Senyawa Volatil Jahe sebagai Agen Sedatif subtitutif ? - aminobutyrate ( GABA ); Kajian Biokomputasi. Prosiding Seminar Nasional Biologi, 7(1), 389–395. https://doi.org/https://doi.org/10.24252/psb.v7i1.24709
Soca?a, K., Szopa, A., Serefko, A., Poleszak, E., & Wla?, P. 2021. Neuroprotective effects of coffee bioactive compounds: A review. International Journal of Molecular Sciences, 22(1), 1–64. https://doi.org/10.3390/ijms22010107
Wasim, S., Kukkar, V., Awad, V. M., Sakhamuru, S., & Malik, B. H. 2020. Neuroprotective and Neurodegenerative Aspects of Coffee and Its Active Ingredients in View of Scientific Literature. Cureus, 12(8), 5–11. https://doi.org/10.7759/cureus.9578
Yuan, G., Gedeon, N. G., Jankins, T. C., & Jones, G. B. 2015. Novel approaches for targeting the adenosine A2A receptor. Expert Opinion on Drug Discovery, 10(1), 63–80. https://doi.org/10.1517/17460441.2015.971006
Zhang, C., Hu, L., Liu, D., Huang, J., & Lin, W. 2020. Circumdatin D Exerts Neuroprotective Effects by Attenuating LPS-Induced Pro-Inflammatory Responses and Downregulating Acetylcholinesterase Activity In Vitro and In Vivo. Frontiers in Pharmacology, 11(May), 1–16. https://doi.org/10.3389/fphar.2020.00760
Auti, S. T., & Kulkarni, Y. A. 2019. Neuroprotective effect of cardamom oil against aluminum induced neurotoxicity in rats. Frontiers in Neurology, 10(APR), 1–17. https://doi.org/10.3389/fneur.2019.00399
Bare, Y., Krisnamurti, G. C., Elizabeth, A., Rachmad, Y. T., Sari, D. R. T., & Gabrella Lorenza, M. R. W. 2019. The potential role of caffeic acid in coffee as cyclooxygenase-2 (COX-2) inhibitor: In silico study. Biointerface Research in Applied Chemistry, 9(5). https://doi.org/10.33263/BRIAC95.424427
Bare, Yohanes, Kuki, A. D., Daeng Tiring, S. S. N., Rophi, A. H., Krisnamurti, G. C., & Sari, D. R. T. 2020. In Silico Study: Prediction the Potential of Caffeic Acid As ACE inhibitor. El-Hayah, 7(3), 94–98. https://doi.org/10.18860/elha.v7i3.10053
Bare, Yohanes, Sari, D. R. T., Rachmad, Y. T., Krisnamurti, G. C., & Elizabeth, A. 2019. In Silico Insight the Prediction of Chlorogenic Acid in Coffee through Cyclooxygenase-2 (COX2) Interaction. Biogenesis: Jurnal Ilmiah Biologi, 7(2), 100–105. https://doi.org/10.24252/bio.v7i2.9847
Bitencourt-Ferreira, G., & de Azevedo, W. F. J. 2019. Molegro Virtual Docker for Docking. Methods in Molecular Biology (Clifton, N.J.), 2053, 149–167. https://doi.org/10.1007/978-1-4939-9752-7_10
Camandola, S., Plick, N., & Mattson, M. P. 2019. Impact of Coffee and Cacao Purine Metabolites on Neuroplasticity and Neurodegenerative Disease. Neurochemical Research, 44(1), 214–227. https://doi.org/10.1007/s11064-018-2492-0
Cheng, R. K. Y., Segala, E., Robertson, N., Deflorian, F., Doré, A. S., Errey, J. C., … Cooke, R. M. 2017. Structures of Human A1 and A2A Adenosine Receptors with Xanthines Reveal Determinants of Selectivity. Structure, 25(8), 1275-1285.e4. https://doi.org/10.1016/j.str.2017.06.012
Cheung, J., Rudolph, M. J., Burshteyn, F., Cassidy, M. S., Gary, E. N., Love, J., … Height, J. J. 2012. Structures of human acetylcholinesterase in complex with pharmacologically important ligands. Journal of Medicinal Chemistry, 55(22), 10282–10286. https://doi.org/10.1021/jm300871x
De Pinho, L. G., Lopes, M. J., Correia, T., Sampaio, F., Do Arco, H. R., Mendes, A., … Fonseca, C. 2021. Patient-centered care for patients with depression or anxiety disorder: An integrative review. Journal of Personalized Medicine, 11(8). https://doi.org/10.3390/jpm11080776
Jaakola, V. P., Griffith, M. T., Hanson, M. A., Cherezov, V., Chien, E. Y. T., Lane, J. R., … Stevens, R. C. 2008. The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist. Science, 322(5905), 1211–1217. https://doi.org/10.1126/science.1164772
Johnston, G. A. R. 2013. Advantages of an antagonist: Bicuculline and other GABA antagonists. British Journal of Pharmacology, 169(2), 328–336. https://doi.org/10.1111/bph.12127
Kolahdouzan, M., & Hamadeh, M. J. 2017. The neuroprotective effects of caffeine in neurodegenerative diseases. CNS Neuroscience and Therapeutics, 23(4), 272–290. https://doi.org/10.1111/cns.12684
Kwon, S. H., Lee, H. K., Kim, J. A., Hong, S. I., Kim, H. C., Jo, T. H., … Jang, C. G. 2010. Neuroprotective effects of chlorogenic acid on scopolamine-induced amnesia via anti-acetylcholinesterase and anti-oxidative activities in mice. European Journal of Pharmacology, 649(1–3), 210–217. https://doi.org/10.1016/j.ejphar.2010.09.001
Liu, Y. H., Lee, C. J., Chen, L. C., Lee, T. L., Hsieh, Y. Y., Han, C. H., … Hou, W. C. 2020. Acetylcholinesterase inhibitory activity and neuroprotection: In vitro, molecular docking, and improved learning and memory functions of demethylcurcumin in scopolamine-induced amnesia ICR mice. Food and Function, 11(3), 2328–2338. https://doi.org/10.1039/c9fo02339a
Lohning, A. E., Marx, W., & Isenring, L. 2016. In silico investigation into the interactions between murine 5-HT3 receptor and the principle active compounds of ginger (Zingiber officinale). Journal of Molecular Graphics and Modelling, 70, 315–327. https://doi.org/10.1016/j.jmgm.2016.10.008
Meng, S., Cao, J., Feng, Q., Peng, J., & Hu, Y. 2013. Roles of chlorogenic acid on regulating glucose and lipids metabolism: A review. Evidence-Based Complementary and Alternative Medicine, 2013. https://doi.org/10.1155/2013/801457
Mondal, P., Gupta, V., Das, G., Pradhan, K., Khan, J., Gharai, P. K., & Ghosh, S. 2018. Peptide-Based Acetylcholinesterase Inhibitor Crosses the Blood-Brain Barrier and Promotes Neuroprotection. ACS Chemical Neuroscience, 9(11), 2838–2848. https://doi.org/10.1021/acschemneuro.8b00253
Motamayor, J. C., Mockaitis, K., Schmutz, J., Haiminen, N., Livingstone, D., Cornejo, O., … Kuhn, D. N. 2013. The genome sequence of the most widely cultivated cacao type and its use to identify candidate genes regulating pod color. Genome Biology, 14(6), r53. https://doi.org/10.1186/gb-2013-14-6-r53
Pires, D. E. V., Blundell, T. L., & Ascher, D. B. 2015. pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of Medicinal Chemistry, 58(9), 4066–4072. https://doi.org/10.1021/acs.jmedchem.5b00104
Putri, S. P., Irifune, T., Yusianto, & Fukusaki, E. 2019. GC/MS based metabolite profiling of Indonesian specialty coffee from different species and geographical origin. Metabolomics, 15(10), 1–11. https://doi.org/10.1007/s11306-019-1591-5
Rath, S. N., Jena, L., Bhuyan, R., Mahanandia, N. C., & Patri, M. 2021. In silico discovery and evaluation of phytochemicals binding mechanism against human Catechol-O-methyltransferase as a putative bioenhancer of L-DOPA therapy in parkinson disease. Genomics and Informatics, 19(1), 1–13. https://doi.org/10.5808/gi.20061
Remya, C., Dileep, K. V., Koti Reddy, E., Mantosh, K., Lakshmi, K., Sarah Jacob, R., … Omkumar, R. V. 2021. Neuroprotective derivatives of tacrine that target NMDA receptor and acetyl cholinesterase – Design, synthesis and biological evaluation. Computational and Structural Biotechnology Journal, 19, 4517–4537. https://doi.org/10.1016/j.csbj.2021.07.041
Sakhuja, Rajeev; Kondabolu, Krishnakanth; Cordova-Sintjago, Tania; Travers, Sean; Vincek, Adam S; Kim, Myong Sang; Abboud, Khalil A.; Fang, Lijuan; Sun, Zhuming; Canal, Clinton E.; Booth, R. G. 2015. Novel 4-Substituted-N,N-dimethyltetrahydronaphthalen-2- amines: Synthesis, Affinity, and In Silico Docking Studies at Serotonin 5-HT2-type and Histamine H1 G Protein-Coupled Receptors. Bioorg Med Chem, 23(7), 1588–1600. https://doi.org/10.1016/j.bmc.2015.01.060
Santomauro, D. F., Mantilla Herrera, A. M., Shadid, J., Zheng, P., Ashbaugh, C., Pigott, D. M., … Ferrari, A. J. 2021. Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic. The Lancet, 398(10312), 1700–1712. https://doi.org/10.1016/s0140-6736(21)02143-7
Sari, Dewi Ratih Tirto; Krisnamurti, G. C. 2021. 1-dehydrogingerdione , Senyawa Volatil Jahe sebagai Agen Sedatif subtitutif ? - aminobutyrate ( GABA ); Kajian Biokomputasi. Prosiding Seminar Nasional Biologi, 7(1), 389–395. https://doi.org/https://doi.org/10.24252/psb.v7i1.24709
Soca?a, K., Szopa, A., Serefko, A., Poleszak, E., & Wla?, P. 2021. Neuroprotective effects of coffee bioactive compounds: A review. International Journal of Molecular Sciences, 22(1), 1–64. https://doi.org/10.3390/ijms22010107
Wasim, S., Kukkar, V., Awad, V. M., Sakhamuru, S., & Malik, B. H. 2020. Neuroprotective and Neurodegenerative Aspects of Coffee and Its Active Ingredients in View of Scientific Literature. Cureus, 12(8), 5–11. https://doi.org/10.7759/cureus.9578
Yuan, G., Gedeon, N. G., Jankins, T. C., & Jones, G. B. 2015. Novel approaches for targeting the adenosine A2A receptor. Expert Opinion on Drug Discovery, 10(1), 63–80. https://doi.org/10.1517/17460441.2015.971006
Zhang, C., Hu, L., Liu, D., Huang, J., & Lin, W. 2020. Circumdatin D Exerts Neuroprotective Effects by Attenuating LPS-Induced Pro-Inflammatory Responses and Downregulating Acetylcholinesterase Activity In Vitro and In Vivo. Frontiers in Pharmacology, 11(May), 1–16. https://doi.org/10.3389/fphar.2020.00760
Downloads
Published
2022-02-22
How to Cite
Sari, D. R. T. ., & Krisnamurti, G. C. . (2022). In Silico Repositioning Strategies of Theobromine and Caffeine for Psychiatric and Neurological Disorders. Proceeding International Conference on Religion, Science and Education, 1, 685–692. Retrieved from http://sunankalijaga.org/prosiding/index.php/icrse/article/view/854
Issue
Section
Articles
