Synthesis and Evaluation of Anti-acetylcholinesterase Activity of 2-(2-(4-(2-Oxo-2-phenylethyl)piperazin-1-yl) ethyl)Isoindoline-1,3-dione Derivatives with Potential Anti-Alzheimer Effects
Objective(s): Alzheimer's disease (AD) is a neurodegenerative disorder in elderly patients. Decrease in cholinergic neurotransmission is the main known cause in the pathophysiology of the disease. Improvement and potentiation of the cholinergic system could be beneficial for treatment of the AD...
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| Format: | Article |
| Language: | English |
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Mashhad University of Medical Sciences
2013-10-01
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| Series: | Iranian Journal of Basic Medical Sciences |
| Subjects: | |
| Online Access: | http://ijbms.mums.ac.ir/pdf_1866_c35e303ca75b2ff194e595de6dd9cad3.html |
| _version_ | 1818787667713720320 |
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| author | Alireza Aliabadi Alireza Foroumadi Ahmad Mohammadi-Farani Mahdi Garmsiri Mahvar |
| author_facet | Alireza Aliabadi Alireza Foroumadi Ahmad Mohammadi-Farani Mahdi Garmsiri Mahvar |
| author_sort | Alireza Aliabadi |
| collection | DOAJ |
| description | Objective(s): Alzheimer's disease (AD) is a neurodegenerative disorder in elderly patients. Decrease in cholinergic neurotransmission is the main known cause in the pathophysiology of the disease. Improvement and potentiation of the cholinergic system could be beneficial for treatment of the AD. Acetylcholinesterase inhibitors such as donepezil can enhance the duration of action of acetylcholine (Ach) and therefore, through this mechanism improve the symptoms of AD. Materials and Methods: In the current study, based on the potential inhibitory activity of phthalimide derivatives towards acetylcholinesterase enzyme, a new series of phthalimide-based compounds were synthesized (4a-4e) and anti-acetylcholinesterase effect was assessed using Ellman's test. Compound 4b with 4-Fluorophenyl moiety was the most potent derivative in this series (IC50
= 16.42 ± 1.07 μM). It was shown that, none of the synthesized compounds showed superior inhibitory potency compared to donepezil (0.41 ± 0.09 μM) as a reference drug.
Conclusion:
The new synthesized phthalimide based analogs could function as potential acetylcholinesterase inhibitors. Further studies are necessary for development of potent analogs. |
| first_indexed | 2024-12-18T14:11:25Z |
| format | Article |
| id | doaj.art-82683110780b4fa985454538e357c3d1 |
| institution | Directory Open Access Journal |
| issn | 2008-3866 2008-3874 |
| language | English |
| last_indexed | 2024-12-18T14:11:25Z |
| publishDate | 2013-10-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj.art-82683110780b4fa985454538e357c3d12022-12-21T21:05:08ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742013-10-011610104910541866Synthesis and Evaluation of Anti-acetylcholinesterase Activity of 2-(2-(4-(2-Oxo-2-phenylethyl)piperazin-1-yl) ethyl)Isoindoline-1,3-dione Derivatives with Potential Anti-Alzheimer EffectsAlireza Aliabadi0Alireza Foroumadi1Ahmad Mohammadi-Farani2Mahdi Garmsiri Mahvar31Novel Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran 2Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran3Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran1Novel Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.4Department of Pharmacology, Toxicology and Medical Services, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran2Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran5Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, IranObjective(s): Alzheimer's disease (AD) is a neurodegenerative disorder in elderly patients. Decrease in cholinergic neurotransmission is the main known cause in the pathophysiology of the disease. Improvement and potentiation of the cholinergic system could be beneficial for treatment of the AD. Acetylcholinesterase inhibitors such as donepezil can enhance the duration of action of acetylcholine (Ach) and therefore, through this mechanism improve the symptoms of AD. Materials and Methods: In the current study, based on the potential inhibitory activity of phthalimide derivatives towards acetylcholinesterase enzyme, a new series of phthalimide-based compounds were synthesized (4a-4e) and anti-acetylcholinesterase effect was assessed using Ellman's test. Compound 4b with 4-Fluorophenyl moiety was the most potent derivative in this series (IC50 = 16.42 ± 1.07 μM). It was shown that, none of the synthesized compounds showed superior inhibitory potency compared to donepezil (0.41 ± 0.09 μM) as a reference drug. Conclusion: The new synthesized phthalimide based analogs could function as potential acetylcholinesterase inhibitors. Further studies are necessary for development of potent analogs.http://ijbms.mums.ac.ir/pdf_1866_c35e303ca75b2ff194e595de6dd9cad3.htmlAcetylcholinesterase Alzheimer Phthalimide Synthesis |
| spellingShingle | Alireza Aliabadi Alireza Foroumadi Ahmad Mohammadi-Farani Mahdi Garmsiri Mahvar Synthesis and Evaluation of Anti-acetylcholinesterase Activity of 2-(2-(4-(2-Oxo-2-phenylethyl)piperazin-1-yl) ethyl)Isoindoline-1,3-dione Derivatives with Potential Anti-Alzheimer Effects Iranian Journal of Basic Medical Sciences Acetylcholinesterase Alzheimer Phthalimide Synthesis |
| title | Synthesis and Evaluation of Anti-acetylcholinesterase Activity of 2-(2-(4-(2-Oxo-2-phenylethyl)piperazin-1-yl) ethyl)Isoindoline-1,3-dione Derivatives with Potential Anti-Alzheimer Effects |
| title_full | Synthesis and Evaluation of Anti-acetylcholinesterase Activity of 2-(2-(4-(2-Oxo-2-phenylethyl)piperazin-1-yl) ethyl)Isoindoline-1,3-dione Derivatives with Potential Anti-Alzheimer Effects |
| title_fullStr | Synthesis and Evaluation of Anti-acetylcholinesterase Activity of 2-(2-(4-(2-Oxo-2-phenylethyl)piperazin-1-yl) ethyl)Isoindoline-1,3-dione Derivatives with Potential Anti-Alzheimer Effects |
| title_full_unstemmed | Synthesis and Evaluation of Anti-acetylcholinesterase Activity of 2-(2-(4-(2-Oxo-2-phenylethyl)piperazin-1-yl) ethyl)Isoindoline-1,3-dione Derivatives with Potential Anti-Alzheimer Effects |
| title_short | Synthesis and Evaluation of Anti-acetylcholinesterase Activity of 2-(2-(4-(2-Oxo-2-phenylethyl)piperazin-1-yl) ethyl)Isoindoline-1,3-dione Derivatives with Potential Anti-Alzheimer Effects |
| title_sort | synthesis and evaluation of anti acetylcholinesterase activity of 2 2 4 2 oxo 2 phenylethyl piperazin 1 yl ethyl isoindoline 1 3 dione derivatives with potential anti alzheimer effects |
| topic | Acetylcholinesterase Alzheimer Phthalimide Synthesis |
| url | http://ijbms.mums.ac.ir/pdf_1866_c35e303ca75b2ff194e595de6dd9cad3.html |
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