Synthesis, docking, pharmacokinetic prediction, and acetylcholinesterase inhibitory evaluation of N-(2-(piperidine-1-yl)ethyl)benzamide derivatives as potential anti-Alzheimer agents
Background and purpose: Alzheimer’s disease is the most common form of dementia and the sixth most common cause of death in the US according to the Alzheimer’s Association. As regards, to date, no effective treatments are available because of the multifactorial nature of the disease, therefore, a la...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Medknow Publications
2024-12-01
|
| Series: | Research in Pharmaceutical Sciences |
| Subjects: | |
| Online Access: | https://journals.lww.com/10.4103/RPS.RPS_257_23 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841556320243679232 |
|---|---|
| author | Ahmad Mohammadi-Farani Farzaneh Moradi Amin Hosseini Alireza Aliabadi |
| author_facet | Ahmad Mohammadi-Farani Farzaneh Moradi Amin Hosseini Alireza Aliabadi |
| author_sort | Ahmad Mohammadi-Farani |
| collection | DOAJ |
| description | Background and purpose:
Alzheimer’s disease is the most common form of dementia and the sixth most common cause of death in the US according to the Alzheimer’s Association. As regards, to date, no effective treatments are available because of the multifactorial nature of the disease, therefore, a large body of recent research has been allocated to the design and development of multi-target-directed ligands that can become effective drug candidates.
Experimental approach:
A novel series of benzamide derivatives (5a-5l) containing piperidine core were synthesized in the current work. After identification of the chemical structures of the members of this series using 1H NMR, IR, and MS spectra, their anti-acetylcholinesterase activity was assessed by the Ellman᾽s test. Docking studies were also performed to investigate the binding mode and determine the interacting amino acids with the corresponding ligands. Finally, the pharmacokinetic (ADME parameters) of the most potent derivative (5d) was predicted and compared with donepezil.
Findings/Results:
Compound 5d possessing the fluorine atom substitution at position ortho was the most active compound in these series (IC50 = 13 ± 2.1 nM). This compound demonstrated superior activity than the reference drug donepezil (IC50 = 0.6 ± 0.05 µM). Molecular docking showed a significant hydrogen bonding of the carbonyl group of compounds 5d with tyrosine 121 into the active site of acetylcholinesterase. Fortunately, this compound showed better promising ADME properties than donepezil.
Conclusion and implication:
The benzamide derivatives introduced in this paper could be proposed as potential anti-acetylcholinesterase. |
| format | Article |
| id | doaj-art-eff535e4c0e144419f985ba508cde2fc |
| institution | Kabale University |
| issn | 1735-5362 1735-9414 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Research in Pharmaceutical Sciences |
| spelling | doaj-art-eff535e4c0e144419f985ba508cde2fc2025-01-07T09:56:57ZengWolters Kluwer Medknow PublicationsResearch in Pharmaceutical Sciences1735-53621735-94142024-12-0119669871110.4103/RPS.RPS_257_23Synthesis, docking, pharmacokinetic prediction, and acetylcholinesterase inhibitory evaluation of N-(2-(piperidine-1-yl)ethyl)benzamide derivatives as potential anti-Alzheimer agentsAhmad Mohammadi-FaraniFarzaneh MoradiAmin HosseiniAlireza AliabadiBackground and purpose: Alzheimer’s disease is the most common form of dementia and the sixth most common cause of death in the US according to the Alzheimer’s Association. As regards, to date, no effective treatments are available because of the multifactorial nature of the disease, therefore, a large body of recent research has been allocated to the design and development of multi-target-directed ligands that can become effective drug candidates. Experimental approach: A novel series of benzamide derivatives (5a-5l) containing piperidine core were synthesized in the current work. After identification of the chemical structures of the members of this series using 1H NMR, IR, and MS spectra, their anti-acetylcholinesterase activity was assessed by the Ellman᾽s test. Docking studies were also performed to investigate the binding mode and determine the interacting amino acids with the corresponding ligands. Finally, the pharmacokinetic (ADME parameters) of the most potent derivative (5d) was predicted and compared with donepezil. Findings/Results: Compound 5d possessing the fluorine atom substitution at position ortho was the most active compound in these series (IC50 = 13 ± 2.1 nM). This compound demonstrated superior activity than the reference drug donepezil (IC50 = 0.6 ± 0.05 µM). Molecular docking showed a significant hydrogen bonding of the carbonyl group of compounds 5d with tyrosine 121 into the active site of acetylcholinesterase. Fortunately, this compound showed better promising ADME properties than donepezil. Conclusion and implication: The benzamide derivatives introduced in this paper could be proposed as potential anti-acetylcholinesterase.https://journals.lww.com/10.4103/RPS.RPS_257_23acetylcholinesterasealzheimer’s diseasepiperidinesynthesis |
| spellingShingle | Ahmad Mohammadi-Farani Farzaneh Moradi Amin Hosseini Alireza Aliabadi Synthesis, docking, pharmacokinetic prediction, and acetylcholinesterase inhibitory evaluation of N-(2-(piperidine-1-yl)ethyl)benzamide derivatives as potential anti-Alzheimer agents Research in Pharmaceutical Sciences acetylcholinesterase alzheimer’s disease piperidine synthesis |
| title | Synthesis, docking, pharmacokinetic prediction, and acetylcholinesterase inhibitory evaluation of N-(2-(piperidine-1-yl)ethyl)benzamide derivatives as potential anti-Alzheimer agents |
| title_full | Synthesis, docking, pharmacokinetic prediction, and acetylcholinesterase inhibitory evaluation of N-(2-(piperidine-1-yl)ethyl)benzamide derivatives as potential anti-Alzheimer agents |
| title_fullStr | Synthesis, docking, pharmacokinetic prediction, and acetylcholinesterase inhibitory evaluation of N-(2-(piperidine-1-yl)ethyl)benzamide derivatives as potential anti-Alzheimer agents |
| title_full_unstemmed | Synthesis, docking, pharmacokinetic prediction, and acetylcholinesterase inhibitory evaluation of N-(2-(piperidine-1-yl)ethyl)benzamide derivatives as potential anti-Alzheimer agents |
| title_short | Synthesis, docking, pharmacokinetic prediction, and acetylcholinesterase inhibitory evaluation of N-(2-(piperidine-1-yl)ethyl)benzamide derivatives as potential anti-Alzheimer agents |
| title_sort | synthesis docking pharmacokinetic prediction and acetylcholinesterase inhibitory evaluation of n 2 piperidine 1 yl ethyl benzamide derivatives as potential anti alzheimer agents |
| topic | acetylcholinesterase alzheimer’s disease piperidine synthesis |
| url | https://journals.lww.com/10.4103/RPS.RPS_257_23 |
| work_keys_str_mv | AT ahmadmohammadifarani synthesisdockingpharmacokineticpredictionandacetylcholinesteraseinhibitoryevaluationofn2piperidine1ylethylbenzamidederivativesaspotentialantialzheimeragents AT farzanehmoradi synthesisdockingpharmacokineticpredictionandacetylcholinesteraseinhibitoryevaluationofn2piperidine1ylethylbenzamidederivativesaspotentialantialzheimeragents AT aminhosseini synthesisdockingpharmacokineticpredictionandacetylcholinesteraseinhibitoryevaluationofn2piperidine1ylethylbenzamidederivativesaspotentialantialzheimeragents AT alirezaaliabadi synthesisdockingpharmacokineticpredictionandacetylcholinesteraseinhibitoryevaluationofn2piperidine1ylethylbenzamidederivativesaspotentialantialzheimeragents |