Synthesis, docking and acetylcholinesterase inhibitory assessment of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives with potential anti-Alzheimer effects

التفاصيل البيبلوغرافية
العنوان: Synthesis, docking and acetylcholinesterase inhibitory assessment of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives with potential anti-Alzheimer effects
المؤلفون: Aram Ahmadi, Hamid Nadri, Ahmad Mohammadi-Farani, Alireza Aliabadi
المصدر: DARU Journal of Pharmaceutical Sciences
بيانات النشر: Springer Science and Business Media LLC, 2013.
سنة النشر: 2013
مصطلحات موضوعية: Synaptic cleft, business.industry, medicine.drug_class, Stereochemistry, Phthalimide, Building and Construction, Isoindoline, Ellman test, Pharmacology, Acetylcholinesterase, Anti-Alzheimer, Docking, Synthesis, chemistry.chemical_compound, chemistry, Acetylcholinesterase inhibitor, Docking (molecular), Medicine, business, Donepezil, Acetylcholinesterase (AChE), Acetylcholine, Research Article, medicine.drug
الوصف: 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 (IC50 = 0.91 ± 0.045 μM) compared to donepezil (IC50 = 0.14 ± 0.03 μM). The results of the enzyme inhibition test (Ellman test) showed that electron withdrawing groups like Cl, F and NO2 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 (IC50 = 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.
تدمد: 2008-2231
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ca39586872e22fd30e1f4bc06af16f3bTest
https://doi.org/10.1186/2008-2231-21-47Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....ca39586872e22fd30e1f4bc06af16f3b
قاعدة البيانات: OpenAIRE