Theoretical Article
Year 2024,
Volume: 4 Issue: 2, 60 - 63, 23.04.2024
Abstract
Cholinesterases are important in ensuring hemostasis in our body. Excessive increase in cholinesterase function causes various cholinergic dysfunctions. Alzheimer's is a disease characterized by loss of cholinergic activity, which is especially common in the elderly. One of the cholinesterase inhibitors most commonly used to stop the progression of Alzheimer's disease is donepezil. Due to some side effects of donepezil, the synthesis and design of new analogues that may be alternatives to donepezil are reported in the literature. In this study, molecular docking studies were performed to compare the in silico AChE inhibitory potential of some new structural analogs of donepezil. Molecular docking studies were performed using Autodock4.2 tools. In this study, the hypothesis emerges that especially compound 1 and compound 5 have the potential to inhibit AChE at least as much as donepezil. In silico docking studies showed that donepezil derivatives designed with bioisosteres of the piperidine ring in donepezil have high binding affinity towards acetylcholine esterase. These results need to be confirmed by synthesis of the donepezil analogues designed in the study and in vitro activity measurements.
Keywords
Acetylcholinesterase Inhibitor bioisostere donepezil Molecular Docking Simulations piperidine
References
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Year 2024,
Volume: 4 Issue: 2, 60 - 63, 23.04.2024
Abstract
References
- 1. Brown JH, Laiken N. Acetylcholine and Muscarinic Receptors. Primer on the Autonomic Nervous System. Elsevier; 2012:75-78. [CrossRef]
- 2. Roy A, Fields WC, Rocha-Resende C, et al. Cardiomyocyte-secreted acetylcholine is required for maintenance of homeostasis in the heart. The FASEB Journal. 2013;27(12):5072. [CrossRef]
- 3. Hasselmo ME. The role of acetylcholine in learning and memory. Current Opinion in Neurobiology. 2006;16(6):710-715. [CrossRef]
- 4. A. S. Acetylcholine. Oxford: Academic Press. 2014;49-50. [CrossRef]
- 5. Krsti DZ, Lazarevi T, Bond A, Vasi V. Acetylcholinesterase inhibitors: Pharmacology and toxicology. Curr Neuropharmacol. 2013;11(3):315-35. [CrossRef]
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- 17. Chernykh AV, Tkachenko AN, Feskov IO, et al. Practical Synthesis of Fluorinated Piperidine Analogues Based on the 2-Azaspiro [3.3] heptane Scaffold. Synlett. 2016;27(12):1824-1827. [CrossRef]
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- 23. Azam SS, Abbasi SW. Molecular docking studies for the identification of novel melatoninergic inhibitors for acetylserotonin-O-methyltransferase using different docking routines. Theoretical Biology and Medical Modelling. 2013;10:1-16. [CrossRef]
- 24. Johnson G, Moore S. The peripheral anionic site of acetylcholinesterase: structure, functions and potential role in rational drug design. Current Pharmaceutical Design. 2006;12(2):217-225. [CrossRef]
- 25. Peitzika S-C, Pontiki E. A review on recent approaches on molecular docking studies of novel compounds targeting acetylcholinesterase in Alzheimer disease. Molecules. 2023;28(3):1084. [CrossRef]
There are 25 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Pharmacology and Pharmaceutical Sciences (Other) |
| Journal Section | Reviews |
| Authors | |
| Publication Date | April 23, 2024 |
| Submission Date | February 1, 2024 |
| Acceptance Date | April 10, 2024 |
| Published in Issue | Year 2024 Volume: 4 Issue: 2 |
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