Cargando…
Synthesis, docking and acetylcholinesterase inhibitory assessment of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives with potential anti-Alzheimer effects
BACKGROUND: Alzheimer’s disease (AD) as neurodegenerative disorder, is the most common form of dementia accounting for about 50-60% of the overall cases of dementia among persons over 65 years of age. Low acetylcholine (ACh) concentration in hippocampus and cortex areas of the brain is one of the ma...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3704662/ https://www.ncbi.nlm.nih.gov/pubmed/23758724 http://dx.doi.org/10.1186/2008-2231-21-47 |
_version_ | 1782276063152308224 |
---|---|
author | Mohammadi-Farani, Ahmad Ahmadi, Aram Nadri, Hamid Aliabadi, Alireza |
author_facet | Mohammadi-Farani, Ahmad Ahmadi, Aram Nadri, Hamid Aliabadi, Alireza |
author_sort | Mohammadi-Farani, Ahmad |
collection | PubMed |
description | BACKGROUND: Alzheimer’s disease (AD) as neurodegenerative disorder, is the most common form of dementia accounting for about 50-60% of the overall cases of dementia among persons over 65 years of age. Low acetylcholine (ACh) concentration in hippocampus and cortex areas of the brain is one of the main reasons for this disease. In recent years, acetylcholinesterase (AChE) inhibitors like donepezil with prevention of acetylcholine hydrolysis can enhance the duration of action of acetylcholine in synaptic cleft and improve the dementia associated with Alzheimer’s disease. RESULTS: Design, synthesis and assessment of anticholinesterase activity of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives showed prepared compounds can function as potential acetylcholinesterase inhibitor. Among 12 synthesized derivatives, compound 4a with ortho chlorine moiety as electron withdrawing group exhibited the highest potency in these series (IC(50) = 0.91 ± 0.045 μM) compared to donepezil (IC(50) = 0.14 ± 0.03 μM). The results of the enzyme inhibition test (Ellman test) showed that electron withdrawing groups like Cl, F and NO(2) can render the best effect at position ortho and para of the phenyl ring. But compound 4g with methoxy group at position 3(meta) afforded a favorable potency (IC(50) = 5.5 ± 0.7 μM). Furthermore, docking study confirmed a same binding mode like donepezil for compound 4a. CONCLUSIONS: Synthesized compounds 4a-4l could be proposed as potential anticholinesterase agents. |
format | Online Article Text |
id | pubmed-3704662 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-37046622013-07-09 Synthesis, docking and acetylcholinesterase inhibitory assessment of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives with potential anti-Alzheimer effects Mohammadi-Farani, Ahmad Ahmadi, Aram Nadri, Hamid Aliabadi, Alireza Daru Research Article BACKGROUND: Alzheimer’s disease (AD) as neurodegenerative disorder, is the most common form of dementia accounting for about 50-60% of the overall cases of dementia among persons over 65 years of age. Low acetylcholine (ACh) concentration in hippocampus and cortex areas of the brain is one of the main reasons for this disease. In recent years, acetylcholinesterase (AChE) inhibitors like donepezil with prevention of acetylcholine hydrolysis can enhance the duration of action of acetylcholine in synaptic cleft and improve the dementia associated with Alzheimer’s disease. RESULTS: Design, synthesis and assessment of anticholinesterase activity of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives showed prepared compounds can function as potential acetylcholinesterase inhibitor. Among 12 synthesized derivatives, compound 4a with ortho chlorine moiety as electron withdrawing group exhibited the highest potency in these series (IC(50) = 0.91 ± 0.045 μM) compared to donepezil (IC(50) = 0.14 ± 0.03 μM). The results of the enzyme inhibition test (Ellman test) showed that electron withdrawing groups like Cl, F and NO(2) can render the best effect at position ortho and para of the phenyl ring. But compound 4g with methoxy group at position 3(meta) afforded a favorable potency (IC(50) = 5.5 ± 0.7 μM). Furthermore, docking study confirmed a same binding mode like donepezil for compound 4a. CONCLUSIONS: Synthesized compounds 4a-4l could be proposed as potential anticholinesterase agents. BioMed Central 2013-06-07 /pmc/articles/PMC3704662/ /pubmed/23758724 http://dx.doi.org/10.1186/2008-2231-21-47 Text en Copyright © 2013 Mohammadi-Farani et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Mohammadi-Farani, Ahmad Ahmadi, Aram Nadri, Hamid Aliabadi, Alireza Synthesis, docking and acetylcholinesterase inhibitory assessment of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives with potential anti-Alzheimer effects |
title | Synthesis, docking and acetylcholinesterase inhibitory assessment of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives with potential anti-Alzheimer effects |
title_full | Synthesis, docking and acetylcholinesterase inhibitory assessment of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives with potential anti-Alzheimer effects |
title_fullStr | Synthesis, docking and acetylcholinesterase inhibitory assessment of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives with potential anti-Alzheimer effects |
title_full_unstemmed | Synthesis, docking and acetylcholinesterase inhibitory assessment of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives with potential anti-Alzheimer effects |
title_short | Synthesis, docking and acetylcholinesterase inhibitory assessment of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives with potential anti-Alzheimer effects |
title_sort | synthesis, docking and acetylcholinesterase inhibitory assessment of 2-(2-(4-benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives with potential anti-alzheimer effects |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3704662/ https://www.ncbi.nlm.nih.gov/pubmed/23758724 http://dx.doi.org/10.1186/2008-2231-21-47 |
work_keys_str_mv | AT mohammadifaraniahmad synthesisdockingandacetylcholinesteraseinhibitoryassessmentof224benzylpiperazin1ylethylisoindoline13dionederivativeswithpotentialantialzheimereffects AT ahmadiaram synthesisdockingandacetylcholinesteraseinhibitoryassessmentof224benzylpiperazin1ylethylisoindoline13dionederivativeswithpotentialantialzheimereffects AT nadrihamid synthesisdockingandacetylcholinesteraseinhibitoryassessmentof224benzylpiperazin1ylethylisoindoline13dionederivativeswithpotentialantialzheimereffects AT aliabadialireza synthesisdockingandacetylcholinesteraseinhibitoryassessmentof224benzylpiperazin1ylethylisoindoline13dionederivativeswithpotentialantialzheimereffects |