Synthesis, characterization, molecular docking, dynamics simulations, and in silico absorption, distribution, metabolism, and excretion (ADME) studies of new thiazolylhydrazone derivatives as butyrylcholinesterase inhibitors
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Ayşen Işık
,
Ismail Celik
Abstract
In this study, two novel series of thiazolylhydrazone derivatives containing 4-ethylpiperazine (3a–3f) and 4-methoxyphenylpiperazine (3g–3l) side chains were synthesized and their structures were characterized by spectral (1H NMR, 13C NMR, and MS spectra) analyses. In vitro inhibitory activities of synthesized compounds against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were determined by Ellman method. According to the results, all compounds showed a weak inhibitory effect on AChE, while promising results were obtained on BChE. Among the synthesized compounds, the activities of the derivatives carrying 4-ethylpiperazine (3a–3f) structure were found to be more effective than the compounds carrying 4-methoxyphenyl piperazine (3g–3l) derivatives. Especially, compound 3f bearing the nitro substituent was found to be the most promising compound on BChE in the series. The absorption, distribution, metabolism, and excretion (ADME) parameters of the synthesized compounds were predicted by using the SwissADME server. The potential binding mode and stability of compound 3f with BChE were investigated by the molecular docking and dynamics simulations. The results showed that 3f was strongly bound up with BChE with the optimal conformation; in addition, their binding free energy reached −167.936 ± 13.109 kJ/mol.
Acknowledgment
Special thanks to WEBGRO Macromolecular Simulations (https://simlab.uams.edu/index.php) for providing high-performance computing for their molecular dynamics simulations.
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Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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Research funding: None declared.
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Conflict of interest statement: The authors declare no conflict of interest.
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Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/znc-2021-0316).
© 2022 Walter de Gruyter GmbH, Berlin/Boston
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Articles in the same Issue
- Frontmatter
- Research Articles
- Synthesis, characterization, molecular docking, dynamics simulations, and in silico absorption, distribution, metabolism, and excretion (ADME) studies of new thiazolylhydrazone derivatives as butyrylcholinesterase inhibitors
- Study on the synthesis and structure-activity relationship of 1,2,3-triazoles against toxic activities of Bothrops jararaca venom
- In-silico elucidation reveals potential phytochemicals against angiotensin-converting enzyme 2 (ACE-2) receptor to fight coronavirus disease 2019 (COVID-19)
- Comparative study of phenolic profile, antioxidant and antimicrobial activities of aqueous extract of white and green tea
- Methylglyoxal and high glucose inhibit VEGFR2 phosphorylation at specific tyrosine residues
- Antidepressant alkaloids from the rhizomes of Corydalis decumbens
- Synthesis of new derivatives containing pyridine, investigation of MAO inhibitory activities and molecular docking studies
- Rapid Communications
- Chemical composition and bioactivities of Magnolia candollii H.Keng essential oil
- Chemical composition and anticholinesterase activity of Lepisanthes rubiginosa (Roxb.) Leenh. essential oil
