Computational Investigation of the Interaction Mechanism of Some anti-Alzheimer Drugs with the Acetylcholinesterase Enzyme

Year 2023, Volume: 8 Issue: 1, 11 - 21, 30.06.2023

Sefa ÇELİK A. Demet DEMİRAG Ali Osman COŞGUN Ayşen ÖZEL Sevim AKYÜZ

https://doi.org/10.56171/ojn.1109606

Abstract

The molecular structures of the lowest-energy conformers of donepezil (C24H29NO3), rivastigmine (C14H22N2O2), and galantamine (C17H21NO3), which are extensively used in Alzheimer's disease and other memory disorders, were identified using the Spartan06 program and the MMFF method. The optimized geometries, obtained with the same method, were used as initial data in molecular docking investigations with the Acetylcholinesterase enzyme. The binding modes, binding affinities, and interactions were comparatively determined as consequence of the calculations.

Keywords

Acetylcholinesterase Enzyme, Alzheimer, Donepezil, Rivastigmine, Galantamine, Molecular docking

Bazı Anti-Alzheimer İlaçlarının Asetilkolinesteraz Enzimiyle Etkileşim Mekanizmasının Hesaplamalı İncelemesi

Abstract

Alzheimer hastalığı ve diğer hafıza bozukluklarında yaygın olarak kullanılan donepezil (C24H29NO3), rivastigmin (C14H22N2O2) ve galantaminin (C17H21NO3) en düşük enerjili konformerlerinin moleküler yapıları Spartan06 programı ve MMFF yöntemi kullanılarak belirlenmiştir. Aynı yöntemle elde edilen optimize geometriler, Asetilkolinesteraz enzimi ile moleküler kenetlenme araştırmalarında başlangıç verisi olarak kullanılmıştır. Hesaplamalar sonucunda bağlanma modları, bağlanma afiniteleri ve etkileşimler karşılaştırmalı olarak belirlenmiştir.

Keywords

Asetilkolinesteraz Enzimi, Alzheimer, Donepezil, Rivastigmin, Galantamin, Moleküler Kenetlenme

References

• 1. Soreq, H., Seidman, S. Acetylcholinesterase — new roles for an old actor. Nature Reviews Neuroscience 2, 294–302 (2001). https://doi.org/10.1038/35067589.
• 2. Villemagne, V. L., Burnham, S., Bourgeat, P., Brown, B., Ellis, K. A., Salvado, O., ... & Masters, C. L. (2013). Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study. The Lancet Neurology, 12(4), 357-367.
• 3. Jack, C. R., Knopman, D. S., Jagust, W. J., Shaw, L. M., Aisen, P. S., & Weiner, M. W. & Trojanowski JQ (2010). Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. The Lancet Neurology, 9(1), 119-128.
• 4. Huang, H. C., & Jiang, Z. F. (2009). Accumulated amyloid-β peptide and hyperphosphorylated tau protein: relationship and links in Alzheimer's disease. Journal of Alzheimer's disease, 16(1), 15-27.
• 5. Iqbal, K., & Grundke-Iqbal, I. (2010). Alzheimer's disease, a multifactorial disorder seeking multitherapies. Alzheimer's & Dementia, 6(5), 420-424.
• 6. Shoghi-Jadid, K., Small, G. W., Agdeppa, E. D., Kepe, V., Ercoli, L. M., Siddarth, P., ... & Barrio, J. R. (2002). Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. The American Journal of Geriatric Psychiatry, 10(1), 24-35.
• 7. De Felice, F. G., Wu, D., Lambert, M. P., Fernandez, S. J., Velasco, P. T., Lacor, P. N., ... & Klein, W. L. (2008). Alzheimer's disease-type neuronal tau hyperphosphorylation induced by Aβ oligomers. Neurobiology of aging, 29(9), 1334-1347.
• 8. Norstrom, E. (2017). Metabolic processing of the amyloid precursor protein—new pieces of the Alzheimer’s puzzle. Discovery Medicine, 23(127), 269-276.
• 9. Edwards III, G., Zhao, J., Dash, P. K., Soto, C., & Moreno-Gonzalez, I. (2020). Traumatic brain injury induces tau aggregation and spreading. Journal of neurotrauma, 37(1), 80-92.
• 10. Kovacs, G. G. (2018). Tauopathies. Handbook of clinical neurology, 145, 355-368.
• 11. Iqbal, K., Liu, F., Gong, C. X., & Grundke-Iqbal, I. (2010). Tau in Alzheimer disease and related tauopathies. Current Alzheimer Research, 7(8), 656-664.
• 12. Panza, F., Lozupone, M., Logroscino, G., & Imbimbo, B. P. (2019). A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease. Nature Reviews Neurology, 15(2), 73-88.
• 13. Doody, R. S., Stevens, J. C., Beck, C., Dubinsky, R. M., Kaye, J. A., Gwyther, L. M. S. W., ... & Cummings, J. L. (2001). Practice parameter: Management of dementia (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 56(9), 1154-1166.
• 14. Frank, L. M., Brown, E. N., & Wilson, M. (2000). Trajectory encoding in the hippocampus and entorhinal cortex. Neuron, 27(1), 169-178.
• 15. Pennanen, C., Kivipelto, M., Tuomainen, S., Hartikainen, P., Hänninen, T., Laakso, M. P., ... & Soininen, H. (2004). Hippocampus and entorhinal cortex in mild cognitive impairment and early AD. Neurobiology of aging, 25(3), 303-310.
• 16. Gómez-Isla, T., Price, J. L., McKeel Jr, D. W., Morris, J. C., Growdon, J. H., & Hyman, B. T. (1996). Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer’s disease. Journal of Neuroscience, 16(14), 4491-4500.
• 17. Eichenbaum, H., & Lipton, P. A. (2008). Towards a functional organization of the medial temporal lobe memory system: role of the parahippocampal and medial entorhinal cortical areas. Hippocampus, 18(12), 1314-1324.
• 18. Goldman-Rakic, P. S. (1996). The prefrontal landscape: implications of functional architecture for understanding human mentation and the central executive. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, 351(1346), 1445-1453.
• 19. Perry, J. (1977). Frege on demonstratives. The philosophical review, 86(4), 474-497.
• 20. PERRY, E. K., Perry, R. H., Blessed, G., & Tomlinson, B. E. (1978). Changes in brain cholinesterases in senile dementia of Alzheimer type. Neuropathology and applied neurobiology, 4(4), 273-277.
• 21. Atack, J. R., Perry, E. K., Bonham, J. R., Perry, R. H., Tomlinson, B. E., Blessed, G., & Fairbairn, A. (1983). Molecular forms of acetylcholinesterase in senile dementia of Alzheimer type: selective loss of the intermediate (10S) form. Neuroscience letters, 40(2), 199-204.
• 22. Fishman, E. B., Siek, G. C., MacCallum, R. D., Bird, E. D., Volicer, L., & Marquis, J. K. (1986). Distribution of the molecular forms of acetylcholinesterase in human brain: alterations in dementia of the Alzheimer type. Annals of neurology, 19(3), 246-252.
• 23. Palmert, M. R., Podlisny, M. B., Witker, D. S., Oltersdorf, T., Younkin, L. H., Selkoe, D. J., & Younkin, S. G. (1989). The beta-amyloid protein precursor of Alzheimer disease has soluble derivatives found in human brain and cerebrospinal fluid. Proceedings of the National Academy of Sciences, 86(16), 6338-6342.
• 24. Zhang, L., Tang, W., Chao, F. L., Zhou, C. N., Jiang, L., Zhang, Y., ... & Tang, Y. (2020). Four-month treadmill exercise prevents the decline in spatial learning and memory abilities and the loss of spinophilin-immunoreactive puncta in the hippocampus of APP/PS1 transgenic mice. Neurobiology of Disease, 136, 104723.
• 25. Çokuğraş, A. N. (2003). Butyrylcholinesterase: structure and physiological importance. Turk J Biochem, 28(2), 54-61.
• 26. Dasarathy, S., & Merli, M. (2016). Sarcopenia from mechanism to diagnosis and treatment in liver disease. Journal of hepatology, 65(6), 1232-1244.
• 27. Walsh, C. T. (1984). Suicide substrates, mechanism-based enzyme inactivators: recent developments. Annual review of biochemistry, 53(1), 493-535.
• 28. Chao, C. C., Hu, S. X., Ehrlich, L., & Peterson, P. K. (1995). Interleukin-1 and tumor necrosis factor-α synergistically mediate neurotoxicity: involvement of nitric oxide and of N-methyl-D-aspartate receptors. Brain, behavior, and immunity, 9(4), 355-365.
• 29. Enz, A., Amstutz, R., Boddeke, H., Gmelin, G., & Malanowski, J. (1993). Brain selective inhibition of acetylcholinesterase: a novel approach to therapy for Alzheimer's disease. Progress in brain research, 98, 431-438.
• 30. Zarotsky, V., Sramek, J. J., & Cutler, N. R. (2003). Galantamine hydrobromide: an agent for Alzheimer’s disease. American journal of health-system pharmacy, 60(5), 446-452.
• 31. McHardy, S. F., Wang, H. Y. L., McCowen, S. V., & Valdez, M. C. (2017). Recent advances in acetylcholinesterase inhibitors and reactivators: an update on the patent literature (2012-2015). Expert opinion on therapeutic patents, 27(4), 455-476.
• 32. Trang, A., & Khandhar, P. B. (2021). Physiology, acetylcholinesterase. In StatPearls [Internet]. StatPearls Publishing.
• 33. McGleenon, B. M., Dynan, K. B., & Passmore, A. P. (1999). Acetylcholinesterase inhibitors in Alzheimer’s disease. British journal of clinical pharmacology, 48(4), 471.
• 34. Lazarevic-Pasti, T., Leskovac, A., Momic, T., Petrovic, S., & Vasic, V. (2017). Modulators of acetylcholinesterase activity: From Alzheimer's disease to anti-cancer drugs. Current medicinal chemistry, 24(30), 3283-3309.
• 35. Mehta, M., Adem, A., & Sabbagh, M. (2012). New acetylcholinesterase inhibitors for Alzheimer's disease. International Journal of Alzheimer’s disease, 2012.
• 36. Gong, C. X., Liu, F., Grundke-Iqbal, I., & Iqbal, K. (2005). Post-translational modifications of tau protein in Alzheimer’s disease. Journal of neural transmission, 112(6), 813-838.
• 37. Komori, T. (1999). Tau‐positive dial Inclusions in Progressive Supranuclear Palsy, Corticobasal Degeneration and Pick's Disease. Brain pathology, 9(4), 663-679.
• 38. Kovacs, G. G. (2019). Molecular pathology of neurodegenerative diseases: principles and practice. Journal of clinical pathology, 72(11), 725-735.
• 39. Iida, M. A., Farrell, K., Walker, J. M., Richardson, T. E., Marx, G. A., Bryce, C. H., ... & Crary, J. F. (2021). Predictors of cognitive impairment in primary age-related tauopathy: an autopsy study. Acta Neuropathologica Communications, 9(1), 1-12.
• 40. Respondek, G., & Höglinger, G. U. (2016). The phenotypic spectrum of progressive supranuclear palsy. Parkinsonism & related disorders, 22, S34-S36.
• 41. Levin, J., Kurz, A., Arzberger, T., Giese, A., & Höglinger, G. U. (2016). The differential diagnosis and treatment of atypical parkinsonism. Deutsches Ärzteblatt International, 113(5), 61.
• 42. Faujan, N. H., Zakaria, N., & Mohammad, N. N. (2019). Molecular docking studies on th e interaction of anti-Alzheimer compounds with amyloid beta peptides. J. Multidiscip. Eeng. Sci. Technol., 6, 132-136.
• 43. Zarini-Gakiye, E., Amini, J., Sanadgol, N., Vaezi, G., & Parivar, K. (2020). Recent updates in the Alzheimer’s disease etiopathology and possible treatment approaches: a narrative review of current clinical trials. Current Molecular Pharmacology, 13(4), 273-294.
• 44. Sugimoto, H., Ogura, H., Arai, Y., Iimura, Y., & Yamanishi, Y. (2002). Research and development of donepezil hydrochloride, a new type of acetylcholinesterase inhibitor. The Japanese journal of pharmacology, 89(1), 7-20.
• 45. Heravi, M. M., & Zadsirjan, V. (2020). Prescribed drugs containing nitrogen heterocycles: An overview. RSC Advances, 10(72), 44247-44311.
• 46. Fowler, A. C. (2020). Pharmaceutical line extensions in the United States. 47. Yan, Z., & Feng, J. (2004). Alzheimer's disease: interactions between cholinergic functions and β-amyloid. Current Alzheimer Research, 1(4), 241-248.
• 48. Howard, R. J., Juszczak, E., Ballard, C. G., Bentham, P., Brown, R. G., Bullock, R., ... & Rodger, M. (2007). Donepezil for the treatment of agitation in Alzheimer's disease. New England Journal of Medicine, 357(14), 1382-1392.
• 49. Hashimoto, M., Kazui, H., Matsumoto, K., Nakano, Y., Yasuda, M., & Mori, E. (2005). Does donepezil treatment slow the progression of hippocampal atrophy in patients with Alzheimer’s disease?. American Journal of Psychiatry, 162(4), 676-682.
• 50. Emre, M., Aarsland, D., Albanese, A., Byrne, E. J., Deuschl, G., De Deyn, P. P., ... & Lane, R. (2004). Rivastigmine for dementia associated with Parkinson's disease. New England Journal of Medicine, 351(24), 2509-2518.
• 51. Ravisankar, P., Parvathi, Y. S., Sri, K. C., Ameen, S. A., Kiranmai, D., Ram, R. S., ... & Babu, P. S. (2017). A Comprehensive Analysis on Different Types of Hypothesis, Diagnosis and Treatment of Alzheimer's Disease. IOSR-JDMS, 16(4), 97-108.
• 52. Hampel, H., Mesulam, M. M., Cuello, A. C., Farlow, M. R., Giacobini, E., Grossberg, G. T., ... & Khachaturian, Z. S. (2018). The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease. Brain, 141(7), 1917-1933.
• 53. Scott, L. J., & Goa, K. L. (2000). Galantamine. Drugs, 60(5), 1095-1122.
• 54. Rodda, J., Morgan, S., & Walker, Z. (2009). Are cholinesterase inhibitors effective in the management of the behavioral and psychological symptoms of dementia in Alzheimer's disease? A systematic review of randomized, placebo-controlled trials of donepezil, rivastigmine and galantamine. International psychogeriatrics, 21(5), 813-824.
• 55. Shanbhag, T., & Shenoy, S. (2015). Pharmacology: Prep Manual for Undergraduates E-book. Elsevier Health Sciences.
• 56. Sugarman, D. E., De Aquino, J. P., Poling, J., & Sofuoglu, M. (2019). Feasibility and effects of galantamine on cognition in humans with cannabis use disorder. Pharmacology Biochemistry and Behavior, 181, 86-92.
• 57. Halgren, T. A. (1996). Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94. Journal of computational chemistry, 17(5‐6), 490-519.
• 58. Shao, Y., Molnar, L. F., Jung, Y., Kussmann, J., Ochsenfeld, C., Brown, S. T., ... & DiStasio Jr, R. A. (2006). Advances in methods and algorithms in a modern quantum chemistry program package. Physical Chemistry Chemical Physics,8(27), 3172-3191.
• 59. Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading.J. Comput. Chem. 2010,31, 455-461.
• 60. Harel, M., Kryger, G., Rosenberry, T. L., Mallender, W. D., Lewis, T., Fletcher, R. J., ... & Sussman, J. L. (2000). Three-dimensional structures of Drosophila melanogaster acetylcholinesterase and of its complexes with two potent inhibitors. Protein Science, 9(6), 1063-1072.
• 61. 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.
• 62. Rodrigues, G. C., Scotti, L., & Scotti, M. (2017). Molecular docking study of triterpenoid azadirachtin A on acetylcholinesterase of Drosophila melanogaster (Diptera: Drosophilidae), MOL2NET, 3, 10.3390/mol2net-03-05054.
• 63. Kondapalli, N., Sruthi, K. (2020). Novel Tacrine and Hesperetin analogues: Design, Molecular docking and in silico ADME studies to identify potential Acetyl choline esterase inhibitors for Alzheimer’s disease. Journal of Faculty of Pharmacy of Ankara University, 44(1), 18-32.
• 64. Rodrigues, G. C. S., dos Santos Maia, M., Silva Cavalcanti, A. B., de Sousa, N. F., Scotti, M. T., & Scotti, L. (2021). In silico studies of lamiaceae diterpenes with bioinsecticide potential against Aphis gossypii and Drosophila melanogaster. Molecules, 26(3), 766.
• 65. NIH, National Library of Medicine, https://pubchem.ncbi.nlm.nih.gov.
• 66. Baskaran, K. P., Arumugam, A., Kandasamy, R., & Alagarsamy, S. (2020). Insilico method for prediction of maximum binding affinity and ligand-protein interaction studies on Alzheimer's disease. Int J Res Granthaalayah, 8(11), 362-370.