Molecular Modelling Studies of Pyridazinone Derivatives as Antibutyrylcholinesterases

Mehmet Abdullah Alagoz; Zeynep Ozdemir; Azime Berna Ozcelik

doi:doi:10.11648/j.ijpc.20190503.11

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Molecular Modelling Studies of Pyridazinone Derivatives as Antibutyrylcholinesterases

Mehmet Abdullah Alagoz, Zeynep Ozdemir, Azime Berna Ozcelik

Published in International Journal of Pharmacy and Chemistry (Volume 5, Issue 3)

Received: 30 July 2019 Accepted: 26 August 2019 Published: 16 September 2019

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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.

Published in	International Journal of Pharmacy and Chemistry (Volume 5, Issue 3)
DOI	10.11648/j.ijpc.20190503.11
Page(s)	26-30
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Butyrylcholinesterase (BChE), Molecular Modelling, Pyridazinone

References

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APA Style

Mehmet Abdullah Alagoz, Zeynep Ozdemir, Azime Berna Ozcelik. (2019). Molecular Modelling Studies of Pyridazinone Derivatives as Antibutyrylcholinesterases. International Journal of Pharmacy and Chemistry, 5(3), 26-30. https://doi.org/10.11648/j.ijpc.20190503.11

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ACS Style

Mehmet Abdullah Alagoz; Zeynep Ozdemir; Azime Berna Ozcelik. Molecular Modelling Studies of Pyridazinone Derivatives as Antibutyrylcholinesterases. Int. J. Pharm. Chem. 2019, 5(3), 26-30. doi: 10.11648/j.ijpc.20190503.11

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AMA Style

Mehmet Abdullah Alagoz, Zeynep Ozdemir, Azime Berna Ozcelik. Molecular Modelling Studies of Pyridazinone Derivatives as Antibutyrylcholinesterases. Int J Pharm Chem. 2019;5(3):26-30. doi: 10.11648/j.ijpc.20190503.11

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@article{10.11648/j.ijpc.20190503.11,
  author = {Mehmet Abdullah Alagoz and Zeynep Ozdemir and Azime Berna Ozcelik},
  title = {Molecular Modelling Studies of Pyridazinone Derivatives as Antibutyrylcholinesterases},
  journal = {International Journal of Pharmacy and Chemistry},
  volume = {5},
  number = {3},
  pages = {26-30},
  doi = {10.11648/j.ijpc.20190503.11},
  url = {https://doi.org/10.11648/j.ijpc.20190503.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijpc.20190503.11},
  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.},
 year = {2019}
}

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TY  - JOUR
T1  - Molecular Modelling Studies of Pyridazinone Derivatives as Antibutyrylcholinesterases
AU  - Mehmet Abdullah Alagoz
AU  - Zeynep Ozdemir
AU  - Azime Berna Ozcelik
Y1  - 2019/09/16
PY  - 2019
N1  - https://doi.org/10.11648/j.ijpc.20190503.11
DO  - 10.11648/j.ijpc.20190503.11
T2  - International Journal of Pharmacy and Chemistry
JF  - International Journal of Pharmacy and Chemistry
JO  - International Journal of Pharmacy and Chemistry
SP  - 26
EP  - 30
PB  - Science Publishing Group
SN  - 2575-5749
UR  - https://doi.org/10.11648/j.ijpc.20190503.11
AB  - 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.
VL  - 5
IS  - 3
ER  -

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Author Information

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

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APA Style

Mehmet Abdullah Alagoz, Zeynep Ozdemir, Azime Berna Ozcelik. (2019). Molecular Modelling Studies of Pyridazinone Derivatives as Antibutyrylcholinesterases. International Journal of Pharmacy and Chemistry, 5(3), 26-30. https://doi.org/10.11648/j.ijpc.20190503.11

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ACS Style

Mehmet Abdullah Alagoz; Zeynep Ozdemir; Azime Berna Ozcelik. Molecular Modelling Studies of Pyridazinone Derivatives as Antibutyrylcholinesterases. Int. J. Pharm. Chem. 2019, 5(3), 26-30. doi: 10.11648/j.ijpc.20190503.11

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AMA Style

Mehmet Abdullah Alagoz, Zeynep Ozdemir, Azime Berna Ozcelik. Molecular Modelling Studies of Pyridazinone Derivatives as Antibutyrylcholinesterases. Int J Pharm Chem. 2019;5(3):26-30. doi: 10.11648/j.ijpc.20190503.11

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@article{10.11648/j.ijpc.20190503.11,
  author = {Mehmet Abdullah Alagoz and Zeynep Ozdemir and Azime Berna Ozcelik},
  title = {Molecular Modelling Studies of Pyridazinone Derivatives as Antibutyrylcholinesterases},
  journal = {International Journal of Pharmacy and Chemistry},
  volume = {5},
  number = {3},
  pages = {26-30},
  doi = {10.11648/j.ijpc.20190503.11},
  url = {https://doi.org/10.11648/j.ijpc.20190503.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijpc.20190503.11},
  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.},
 year = {2019}
}

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TY  - JOUR
T1  - Molecular Modelling Studies of Pyridazinone Derivatives as Antibutyrylcholinesterases
AU  - Mehmet Abdullah Alagoz
AU  - Zeynep Ozdemir
AU  - Azime Berna Ozcelik
Y1  - 2019/09/16
PY  - 2019
N1  - https://doi.org/10.11648/j.ijpc.20190503.11
DO  - 10.11648/j.ijpc.20190503.11
T2  - International Journal of Pharmacy and Chemistry
JF  - International Journal of Pharmacy and Chemistry
JO  - International Journal of Pharmacy and Chemistry
SP  - 26
EP  - 30
PB  - Science Publishing Group
SN  - 2575-5749
UR  - https://doi.org/10.11648/j.ijpc.20190503.11
AB  - 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.
VL  - 5
IS  - 3
ER  -

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