DOI: https://doi.org/10.14710/jksa.25.3.97-107

In Silico Screening of Cinnamon (Cinnamomum burmannii) Bioactive Compounds as Acetylcholinesterase Inhibitors

Department of Biochemistry, Faculty of Mathematics and Natural Sciences, IPB University, Bogor, 16680, Indonesia

Received: 18 Dec 2021; Revised: 2 Mar 2022; Accepted: 8 Mar 2022; Published: 31 Mar 2022.
Open Access Copyright 2022 Jurnal Kimia Sains dan Aplikasi under http://creativecommons.org/licenses/by-sa/4.0.

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Abstract
Alzheimer’s is a progressive and neurodegenerative disease that mainly affects people aged 65 years and older. The pathophysiology of Alzheimer’s is possibly related to the depletion of the neurotransmitter acetylcholine (ACh) due to beta-amyloid plaques and neurofibrillary tangles. Secondary metabolites found in cinnamon bark (Cinnamomum burmannii) have the potential as anticholinesterases to treat Alzheimer’s symptoms. This study aimed to identify the potency of bioactive compounds from cinnamon bark as AChE inhibitors in silico through analysis of binding energy, inhibition constants, and types of interactions. The research was conducted by screening virtually 60 test ligands using the PyRx program and molecular docking using the Autodock Tools program. The results of the ligand-receptor interaction analysis showed that 12 of the 15 tested ligands had potential as AChE inhibitors. Epicatechin and medioresinol are the ligands with the best potential for AChE inhibition with affinity close to the natural ligand or donepezil. Epicatechin has a binding energy of −10.0 kcal/mol and inhibition constant of 0.0459 M, with four hydrogen bonds and seven hydrophobic bonds. Meanwhile, medioresinol has −9.9 kcal/mol binding energy and inhibition constant of 0.0543 M, with one hydrogen bond and thirteen hydrophobic bonds.
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Keywords: Alzheimer; acetylcholinesterase; cinnamon; molecular docking
Funding: Institut Pertanian Bogor

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Section: Research Articles
Language : EN
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  1. Indu Bhushan, Manjot Kour, Guneet Kour, Shriya Gupta, Supriya Sharma, Arvind Yadav, Alzheimer’s disease: Causes & treatment–A review, Annals of Biotechnology, 1, 1, (2018), 1-8 http://dx.doi.org/10.33582/2637-4927/1002
  2. Anil Kumar Singhal, Vijay Naithani, Om Prakash Bangar, Medicinal plants with a potential to treat Alzheimer and associated symptoms, International Journal of Nutrition, Pharmacology, Neurological Diseases, 2, 2, (2012), 84-91 https://doi.org/10.4103/2231-0738.95927
  3. lzheimer’s Disease International, World Alzheimer Report 2021. Journey through the diagnosis of dementia, Alzheimer’s Disease International, London, 2021
  4. lzheimer’s Indonesia, Statistik tentang demensia, 2019
  5. Begüm Nurpelin Sağlık, Serkan Levent, Derya Osmaniye, Ulviye Acar Çevik, Betül Kaya Çavuşoğlu, Yusuf Özkay, Ali Savaş Koparal, Zafer Asım Kaplancıklı, Design, synthesis, and biological activity evaluation of new donepezil-like compounds bearing thiazole ring for the treatment of Alzheimer’s disease, Crystals, 10, 8, (2020), 637 https://doi.org/10.3390/cryst10080637
  6. Jagmohan Sharma, K. Ramanathan, Rao Sethumadhavan, Identification of potential inhibitors against acetylcholinesterase associated with Alzheimer's diseases: a molecular docking approach, Journal of Computational Methods in Molecular Design, 1, 1, (2011), 44-51
  7. Kamlesh Sharma, Cholinesterase inhibitors as Alzheimer's therapeutics (Review), Molecular Medicine Reports, 20, 2, (2019), 1479-1487 https://doi.org/10.3892/mmr.2019.10374
  8. Mery Budiarti, Wahyu Jokopriambodo, Ani Isnawati, Karakterisasi minyak atsiri dari simplisia basah ranting dan daun sebagai alternatif subtitusi kulit batang cinnamomum burmannii blume, Jurnal Kefarmasian Indonesia, (2018), 125-136 https://doi.org/10.22435/jki.v8i2.323
  9. Aleix Gimeno, María José Ojeda-Montes, Sarah Tomás-Hernández, Adrià Cereto-Massagué, Raúl Beltrán-Debón, Miquel Mulero, Gerard Pujadas, Santiago Garcia-Vallvé, The light and dark sides of virtual screening: what is there to know?, International Journal of Molecular Sciences, 20, 6, (2019), 1-24 https://doi.org/10.3390/ijms20061375
  10. Eduardo Habib Bechelane Maia, Letícia Cristina Assis, Tiago Alves De Oliveira, Alisson Marques Da Silva, Alex Gutterres Taranto, Structure-based virtual screening: from classical to artificial intelligence, Frontiers in Chemistry, 8, (2020), 343 https://doi.org/10.3389/fchem.2020.00343
  11. Fauzan Zein Muttaqin, Wayan Ayu Puje Astuti, Ellin Febrina, Aiyi Asnawi, Penapisan Virtual Berbasis Struktur dari Database Bahan Alam Zinc Sebagai Inhibitor Bruton Tyrosine Kinase, Jurnal Ilmiah Ibnu Sina, 4, 2, (2019), 400-409
  12. Madhu Katyayani Balijepalli, Ayuba Sunday Buru, Raghavendra Sakirolla, Mallikarjuna Rao Pichika, Cinnamomum genus: A review on its biological activities, International Journal of Pharmacy and Pharmaceutical Sciences, 9, 2, (2017), 1-11
  13. Edward J. Okello, Joshua Mather, Comparative kinetics of acetyl-and butyryl-cholinesterase inhibition by green tea catechins| relevance to the symptomatic treatment of Alzheimer’s disease, Nutrients, 12, 4, (2020), 1090 https://doi.org/10.3390/nu12041090
  14. Helen M. Berman, John Westbrook, Zukang Feng, Gary Gilliland, Talapady N. Bhat, Helge Weissig, Ilya N. Shindyalov, Philip E. Bourne, The protein data bank, Nucleic Acids Research, 28, 1, (2000), 235-242 https://doi.org/10.1093/nar/28.1.235
  15. Minky Son, Chanin Park, Shailima Rampogu, Amir Zeb, Keun Woo Lee, Discovery of novel acetylcholinesterase inhibitors as potential candidates for the treatment of Alzheimer’s disease, International Journal of Molecular Sciences, 20, 4, (2019), 1-15 https://doi.org/10.3390/ijms20041000
  16. Muhammad Fakhruri, Yuni Rahmayanti, Potensi Fitokimia Citrus Aurantium (Hesperetin, Naringenin) dalam Menghambat Xantin Okisidase Pada Hiperurisemia Secara In Silico, Jurnal Health Sains, 2, 1, (2021), 79-89
  17. Garrett M. Morris, Ruth Huey, William Lindstrom, Michel F. Sanner, Richard K. Belew, David S. Goodsell, Arthur J. Olson, AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility, Journal of Computational Chemistry, 30, 16, (2009), 2785-2791 https://doi.org/10.1002/jcc.21256
  18. Roman A. Laskowski, Malcolm W. MacArthur, David S. Moss, Janet M. Thornton, PROCHECK: a program to check the stereochemical quality of protein structures, Journal of Applied Crystallography, 26, 2, (1993), 283-291 https://doi.org/10.1107/S0021889892009944
  19. Christopher A. Lipinski, Lead-and drug-like compounds: the rule-of-five revolution, Drug Discovery Today: Technologies, 1, 4, (2004), 337-341 https://doi.org/10.1016/j.ddtec.2004.11.007
  20. Peter Juma Ochieng, Tony Sumaryada, Daniel Okun, Molecular docking and pharmacokinetic prediction of herbal derivatives as maltase-glucoamylase inhibitor, Asian Journal of Pharmaceutical and Clinical Research, 10, 9, (2017), 392-398 https://doi.org/10.22159/ajpcr.2017.v10i9.19337
  21. Oleg Trott, Arthur J. Olson, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, Journal of Computational Chemistry, 31, 2, (2010), 455-461 https://doi.org/10.1002/jcc.21334
  22. Christopher Llynard D. Ortiz, Gladys C. Completo, Ruel C. Nacario, Ricky B. Nellas, Potential inhibitors of galactofuranosyltransferase 2 (GlfT2): Molecular docking, 3D-QSAR, and in silico ADMETox Studies, Scientific Reports, 9, 1, (2019), 1-28 https://doi.org/10.1038/s41598-019-52764-8
  23. Jonah Cheung, Ebony N. Gary, Kazuro Shiomi, Terrone L. Rosenberry, Structures of human acetylcholinesterase bound to dihydrotanshinone I and territrem B show peripheral site flexibility, ACS Medicinal Chemistry Letters, 4, 11, (2013), 1091-1096 https://doi.org/10.1021/ml400304w
  24. Changdev G. Gadhe, Anand Balupuri, Seung Joo Cho, In silico characterization of binding mode of CCR8 inhibitor: homology modeling, docking and membrane based MD simulation study, Journal of Biomolecular Structure and Dynamics, 33, 11, (2015), 2491-2510 https://doi.org/10.1080/07391102.2014.1002006
  25. Bosco K. Ho, Robert Brasseur, The Ramachandran plots of glycine and pre-proline, BMC Structural Biology, 5, 1, (2005), 1-11 https://doi.org/10.1186/1472-6807-5-14
  26. Oliviero Carugo, K. Djinović-Carugo, Half a century of Ramachandran plots, Acta Crystallographica Section D: Biological Crystallography, 69, 8, (2013), 1333-1341 https://doi.org/10.1107/S090744491301158X
  27. Gita Syahputra, Simulasi docking kurkumin enol, bisdemetoksikurkumin dan analognya sebagai inhibitor enzim12-lipoksigenase, Jurnal Biofisika, 10, 1, (2014), 55-67
  28. Christopher A. Lipinski, Franco Lombardo, Beryl W. Dominy, Paul J. Feeney, Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings, Advanced Drug Delivery Reviews, 23, 1-3, (1997), 3-25 https://doi.org/10.1016/S0169-409X(00)00129-0
  29. Xiaochun Wu, Lloyd R. Whitfield, Barbra H. Stewart, Atorvastatin transport in the Caco-2 cell model: contributions of P-glycoprotein and the proton-monocarboxylic acid co-transporter, Pharmaceutical Research, 17, 2, (2000), 209-215 https://doi.org/10.1023/A:1007525616017
  30. Violeta Ivanović, Miroslav Rančić, Biljana Arsić, Aleksandra Pavlović, Lipinski’s rule of five, famous extensions and famous exceptions, Chemia Naissensis, 3, 1, (2020), 171-177
  31. Loita Datu Nindita, Modeling Hubungan Kuantitatif Struktur Dan Aktivitas (HKSA) Pinocembrin Dan Turunannya Sebagai Anti Kankermodelling a Quantitative Structure and Activity Relationship (QSAR) in Pinocembrin and Its Derivative as the Anti-Cancer, UNESA Journal of Chemistry, 3, 2, (2014), 26-34
  32. Shawn M. Lamothe, Jun Guo, Wentao Li, Tonghua Yang, Shetuan Zhang, The human ether-a-go-go-related gene (hERG) potassium channel represents an unusual target for protease-mediated damage, Journal of Biological Chemistry, 291, 39, (2016), 20387-20401 https://doi.org/10.1074/jbc.M116.743138
  33. James E. Klaunig, Chemical Carcinogenesis, in: C.D. Klaassen (Ed.) Casarett and Doull's Toxicology: The Basic Science of Poisons (8th edition), McGraw-Hill Education, New York, 2013
  34. Vincent James Cogliano, Robert Baan, Kurt Straif, Yann Grosse, Béatrice Lauby-Secretan, Fatiha El Ghissassi, Véronique Bouvard, Lamia Benbrahim-Tallaa, Neela Guha, Crystal Freeman, Laurent Galichet, Christopher P. Wild, Preventable Exposures Associated With Human Cancers, JNCI: Journal of the National Cancer Institute, 103, 24, (2011), 1827-1839 https://doi.org/10.1093/jnci/djr483
  35. Yesi Astri, Truly Sitorus, Joseph I. Sigit, Muchtan Sujatno, Toksisitas Akut per Oral Ekstrak Etanol Daun Dewa (Gynura pseudochina (Lour.) DC) terhadap Kondisi Lambung Tikus Jantan dan Betina Galur Wistar, Majalah Kedokteran Bandung, 44, 1, (2012), 38-43 http://dx.doi.org/10.15395/mkb.v44n1.71
  36. Dave Eaton, Steven G. Gilbert, Principles of Toxicology, in: C.D. Klaassen (Ed.) Casarett & Doull’s Toxicology: The Basic Science of Poisons (8th edition), McGraw-Hill Education, New York, 2013
  37. Xiao Li, Lei Chen, Feixiong Cheng, Zengrui Wu, Hanping Bian, Congying Xu, Weihua Li, Guixia Liu, Xu Shen, Yun Tang, In silico prediction of chemical acute oral toxicity using multi-classification methods, Journal of Chemical Information and Modeling, 54, 4, (2014), 1061-1069 https://doi.org/10.1021/ci5000467
  38. J. Christian Baber, David C. Thompson, Jason B. Cross, Christine Humblet, GARD: a generally applicable replacement for RMSD, Journal of Chemical Information and Modeling, 49, 8, (2009), 1889-1900 https://doi.org/10.1021/ci9001074
  39. Nursamsiar Nursamsiar, Maya M. Mangande, Akbar Awaluddin, Syamsu Nur, Aiyi Asnawi, In Silico Study of Aglycon Curculigoside A and Its Derivatives as α-Amilase Inhibitors, Indonesian Journal of Pharmaceutical Science and Technology, 7, 1, (2020), 29-37 https://doi.org/10.24198/ijpst.v7i1.23062
  40. Mohd Ahmar Rauf, Swaleha Zubair, Asim Azhar, Ligand docking and binding site analysis with PyMOL and Autodock/Vina, International Journal of Basic and Applied Sciences, 4, 2, (2015), 168 https://doi.org/10.1007/s10822-010-9352-6
  41. Syed Sikander Azam, Sumra Wajid Abbasi, Molecular docking studies for the identification of novel melatoninergic inhibitors for acetylserotonin-O-methyltransferase using different docking routines, Theoretical Biology and Medical Modelling, 10, 1, (2013), 1-16 https://doi.org/10.1186/1742-4682-10-63
  42. Shibaji Ghosh, Kalyanashis Jana, Bishwajit Ganguly, Revealing the mechanistic pathway of cholinergic inhibition of Alzheimer's disease by donepezil: a metadynamics simulation study, Physical Chemistry Chemical Physics, 21, 25, (2019), 13578-13589 https://doi.org/10.1039/C9CP02613D
  43. Danna De Boer, Nguyet Nguyen, Jia Mao, Jessica Moore, Eric J. Sorin, A comprehensive review of cholinesterase modeling and simulation, Biomolecules, 11, 4, (2021), 1-35 https://doi.org/10.3390/biom11040580
  44. Mariyana Atanasova, Nikola Yordanov, Ivan Dimitrov, Strahil Berkov, Irini Doytchinova, Molecular docking study on galantamine derivatives as cholinesterase inhibitors, Molecular Informatics, 34, 6 7, (2015), 394-403 https://doi.org/10.1002/minf.201400145
  45. Rollando Rollando, Pendekatan Struktur Aktivitas dan Penambatan Molekul Senyawa 2-iminoethyl 2-(2-(1-hydroxypentan-2-yl) phenyl) acetate Hasil Isolasi Fungi Endofit Genus Fusarium sp pada Enzim β-ketoasil-ACP KasA Sintase, Pharmaceutical Journal of Indonesia, 3, 2, (2018), 45-51 http://dx.doi.org/10.21776/ub.pji.2017.003.02.2
  46. George A. Jeffrey, An introduction to hydrogen bonding, Oxford University Press New York, 1997
  47. Thomas Balle, Tommy Liljefors, Molecular Recognition, in: K. Stromgaard, P. Krogsgaard-Larsen, U. Madsen (Eds.) Textbook of Drug Design and Discovery (5th edition), 2017
  48. Yaghoub Pourshojaei, Ardavan Abiri, Razieh Eskandari, Fatemeh Dourandish, Khalil Eskandari, Ali Asadipour, Synthesis, biological evaluation, and computational studies of novel fused six-membered O-containing heterocycles as potential acetylcholinesterase inhibitors, Computational Biology and Chemistry, 80, (2019), 249-258 https://doi.org/10.1016/j.compbiolchem.2019.04.004
  49. Arwansyah Arwansyah, Laksmi Ambarsari, Tony I. Sumaryada, Simulasi docking senyawa kurkumin dan analognya sebagai inhibitor reseptor androgen pada kanker prostat, Current Biochemistry, 1, 1, (2014), 11-19
  50. Doni Dermawan, Riyadi Sumirtanurdin, Deti Dewantisari, Molecular Dynamics Simulation Estrogen Receptor Alpha againts Andrographolide as Anti Breast Cancer, Indonesian Journal of Pharmaceutical Science and Technology, 6, 2, (2019), 65-76 https://doi.org/10.24198/ijpst.v6i2.18168

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