Volume 5, Issue 3, May 2019, Page: 26-30
Molecular Modelling Studies of Pyridazinone Derivatives as Antibutyrylcholinesterases
Mehmet Abdullah Alagoz, Department of Pharmaceutical Chemistry, Inonu University Faculty of Pharmacy, Malatya, Turkey
Zeynep Ozdemir, Department of Pharmaceutical Chemistry, Inonu University Faculty of Pharmacy, Malatya, Turkey
Azime Berna Ozcelik, Department of Pharmaceutical Chemistry, Gazi University Faculty of Pharmacy, Malatya, Turkey
Received: Jul. 30, 2019;       Accepted: Aug. 26, 2019;       Published: Sep. 16, 2019
DOI: 10.11648/j.ijpc.20190503.11      View  42      Downloads  20
Abstract
Background: Butyrylcholinesterase (BChE) is known serine hydrolase enzymes responsible for the hydrolysis of acetylcholine (ACh). Although the role of the other serine hydrolase enzyme, acetylcholinesterase (AChE) in cholinergic transmission is well known, the role of BChE has not been elucidated sufficiently. The hydrolysis of acetylcholine in the synaptic healthy brain cells mainly carried out by AChE, it is accepted that contribution to the hydrolysis of BChE is very low; but both AChE and BChE are known to play an active role in neuronal development and cholinergic transmission. Docking is a method that predicts the preferential orientation of a molecule (small molecule) to a second (protein) molecule when connected to form a stable complex. It is used to predict the affinity of small molecule drug candidates against protein targets, their binding to these proteins, and hence their biological activity. Objective: In this study, we examined a series of pyridazinone-derived compounds, previously synthesized by our research group, for the compatibility of BChE enzyme and some physicochemical properties of the compounds in silico. Method: The compounds were optimized by conjugated gradient method by creating three dimensional models with OPLS_2005 force field parameters with 2D Sketcher and MacroModel (Schrödinger, LLC, NY) software in Maestro (Schrödinger, LLC, NY). Results: When the activities of the compounds were compared with the physicochemical parameters calculated by computerized methods, some parameters were found to be directly related to the activity. Conclusion: This study supports that the researchers may use to calculate various physicochemical properties and to make molecular modeling studies before working with pyridazinone derivates.
Keywords
Butyrylcholinesterase (BChE), Molecular Modelling, Pyridazinone
To cite this article
Mehmet Abdullah Alagoz, Zeynep Ozdemir, Azime Berna Ozcelik, Molecular Modelling Studies of Pyridazinone Derivatives as Antibutyrylcholinesterases, International Journal of Pharmacy and Chemistry. Vol. 5, No. 3, 2019, pp. 26-30. doi: 10.11648/j.ijpc.20190503.11
Copyright
Copyright © 2019 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Reference
[1]
A. Imramovsky, V. Pejchal, S. Štepankova, K. Vorcakova, J. Jampilek, J. Vanco, P. Šimunek, K. Kralovec, L. Bruckova, J. Mandikova, and F. Trejtnar, “Synthesis and in vitro evaluation of new derivatives of 2- substituted-6- fluorobenzo [d] thiazoles as cholinesterase inhibitors,” Bioorg. Med. Chem. vol. 21, pp. 1735–1748, 2013.
[2]
S. Darvesh, D. L. Grantham, and D. A. Hopkins, “Distribution of butyrylcholinesterase in the human amygdala,” J. Comp. Neurol. vol.393, pp. 374-390, 1998.
[3]
M. M. Mesulam, A. Guillozet, P. Shaw, A. Levey, E. G. Duysen, and O. Lockridge, “Acetylcholinesterase knockouts establish central cholinergic pathways and can use butyrylcholinesterase to hydrolyze acetylcholine,” Neurosci. vol. 110 (4), pp. 627-639, 2002
[4]
N. H. Greig, T. Utsuki, Q. Yu, X. Zhu, H. W. Holloway, T. Perry, B. Lee, D. K. Ingram, and D. K. Lahiri, “A new therapeutic target in Alzheimer's disease treatment: Attention to butyrylcholinesterase,” Curr. Med. Res. Opin. vol. 17 (3), pp. 159-165, 2001.
[5]
M. Mehta, A. Adem, and M. Sabbagh, “New acetylcholinesterase inhibitors for Alzheimer’s disease,” Int. J. Alzheimers Dis. https:/org/10.1155/2012/728983, 2012.
[6]
A. Chatonnet, and O. Lockridge, “Comparison of butyrylcholinesterase and acetylcholinesterase,” Biochem. J. vol. 260 (3), pp. 625-634, 1989. B.
[7]
W. Liu, H. Wang, X. Li, Y. Xu, J. Zhang, W. Wang, Q. Gong, X. Qiu, J. Zhu, F. Mao, H. Zhang, and J. Li “Design, synthesis and evaluation of vilazodone-International Journal of Pharmacy and Chemistry tacrine hybrids as multitarget-directed ligands against depression with cognitive impairment,” Bioorg. Med. Chem. vol. 26 (12), pp. 3117-3125, 2018.
[8]
K. Lao, N. Ji, X. Zhang, W. Qiao, and Z. Tang, “Drug development for Alzheimer’s disease: review,” J. Drug Target. https://doi.org/10.1080/1061186X.2018.1474361, 2018.
[9]
P. Anand, and P. Singh, “A review on cholinesterase inhibitors for Alzheimer’s disease,” Arch. Pharm. Res. vol. 36, pp. 375–399, 2013.
[10]
A. Anand, A. A. Patience, N. Sharma, and N. Khuran, “The present and future of pharmacotherapy of Alzheimer’s disease: A comprehe nsive review.” Eur. J. Pharmacol. vol. 815, pp. 364–375, 2017.
[11]
A. B. Özçelik, M. Gökçe, İ. Orhan, F. Kaynak, and M. F. Şahin, “Synthesis and antimicrobial, acetylcholinesterase and butyryl cholinesterase inhibitory avtivities of novel ester and derivatives of 3(2H)-pyridazinone,” Arzneim. Forsch. vol. 60 (7), pp. 452–458, 2010.
[12]
J. L. Banks, H. S. Beard, Y. X. Cao, A. E. Cho, W. Damm, R. Farid, A. K. Felts, T. A. Halgren, D. T. Mainz, J. R. Maple, R. Murphy, D. M. Phillipp, M. P. Repasky, L. Y. Zhang, B. J. Berne, R. A. Friesner, E. Gallicchio, and R. M. Levy, Integrated modeling program, applied chemical theory (IMPACT),” J. Comput. Chem. vol. 26, pp. 1752–1780, 2005.
[13]
H. M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T. N. Bhat, H. Weissig, I. N. Shindyalov, and P. E. Bourne, “The Protein Data Bank,” Nucleic Acids Res. vol. 28, pp. 235-242, 2000.
[14]
R. A. Friesner, R. B. Murphy, M. P. Repasky, L. L. Frye, J. R. Greenwood, T. A. Halgren, P. C. Sanschagrin, and D. T. Mainz, “Extra Precision Glide: Docking and Scoring Incorporating a Model of Hydrophobic Enclosure for Protein-Ligand Complexes,” J. Med. Chem. vol. 49, pp. 6177–6196, 2006.
[15]
R. A. Friesner, J. L. Banks, R. B. Murphy, T. A. Halgren, J. J. Klicic, D. T. Mainz, M. P. Repasky, E. H. Knoll, M. Shelley, J. K. Perry, D. E. Shaw, P. Francis, and P. S. Shenkin, “Glide: a new approach for rapid, accurate docking and scoring. 1. Method and Assessment of Docking Accuracy,” J. Med. Chem. vol. 47 (7), pp. 1739–1749, 2004.
[16]
T. A. Halgren, R. B. Murphy, R. A. Friesner, H. S. Beard, L. L. Frye, W. T. Pollard, and J. L. Banks, “Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening,” J. Med. Chem. vol. 47 (7), pp. 1750–1759, 2004.
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