جستجوی مقالات مرتبط با کلیدواژه « acetylcholinesterase » در نشریات گروه « علوم »

Based on the important interactions of donepezil with cholinesterase receptor, a series of coumarin-based N-benzyl pyridinium derivatives (5a-l) were synthesized and had in-vitro evaluation for their acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities. It was revealed that compound 5l with plausible IC50 values of 0.247 µM and 1.68 µM on AChE and BuChE, respectively was the most potent anticholinesterase inhibitor compared to other synthesized compounds. The enzyme kinetic assay of compound 5l was conducted on the AChE enzyme and the compound 5l was found to be a non-competitive inhibitor of the AChE (Ki= 0.356). In addition, the compound 5l remarkably protected PC12 neurons against H2O2-induced cell death. The docking study of compound 5l revealed that the inhibitor occupied both CAS and PAS binding sites of the AChE enzyme. we have synthesized 12 products in two steps reactions and high to moderate yields. The first step involves the nucleophilic substitution reaction between 4-hydroxycoumarin and pyridyl chloride (3-pyridinium and 4-pyridinium) derivatives, which produces an intermediate of 3. Following the reaction of this intermediate with benzyl chloride derivatives, led to the synthesis of final products 5. The results were compared with donepezil and tacrine as standard drugs for AChE and BuChE inhibitory assays. Based on the IC50 values, the tendency to inhibit synthetic compounds in final products for AChE is better than BuChE. Among the products in AChE inhibitory assay, the 3-pyridinium series showed more effectiveness than the 4-pyridinium series. Docking studies and product interactions with cholinesterase receptor active sites clearly show the role of 3-pyridinium derivatives in receptor binding.

Alzheimer's disease is an irreversible chronic neurodegenerative disease which is the most common cause of dementia among older adults. According to amyloid hypothesis, cholin neurotransmitters have important roles in CNS memory function, therefore cholinesterase inhibitors can improve the Alzheimer's symptoms. In recent decades, marine creatures have become interested for their huge medicinal effects and potential of pharmaceutical preparations. Marine classifications contain pharmacologically active compounds with capibilities for improvement of cognitive disorders. This article provides a comprehensive overview of cholinesterase inhibitors from marines in 4 categories contain seaweeds, marine sponges, coelenterates and other invertebrates over the 47 years from 1970 to 2017 which resulted into important bioactive extracts and isolated compounds which representing a diverse range of structural classes such as pyrrole derivatives, sesquiterpene acetates, tetrazacyclopentazulene, bromotyrosine derivatives, plastoquinones, farnesylacetones and poly-alkylpyridinium polymers (Poly-APS). For each structural group, the important compounds with cholinesterase inhibition activities were introduced. The result showed marins can be considered as important sources to discover new cholinesterase inhibitiors.

Inhibition of acetylcholinesterase and butyrylcholinesterase (AChE and BuChE) as two major forms of cholinesterases (ChEs) is considered as the common approach for the treatment of Alzheimer's disease (AD). The present study was done to explore the anticholinesterase inhibition property of coumarin Mannich base derivatives. A series of cumarin Manich bases were synthesized (4a-h) through one-pot tri-component reaction in an environmentally friendly condition and evaluated against AChE and BuChE by Ellman's assay. Ligand-protein docking simulation was also performed for the most active compound 4a. Additionally, the criteria of drug likeness of the target compounds was predicted using SwissADME web service. All compounds exhibited weak to moderate inhibitory activity against both AChE and BuChE enzymes. Compound 4a containing p-tolyl piperazin group showed the best activity against AChE (42.4 % at 32 µM), while compound 4g bearing phenylpiperazine moiety was the best BuChE inhibitor (43.9% at 32 µM). Ligand-protein docking simulation also exhibited that the main part of compound 4a in ChE inhibitory activity is amine moiety. Moreover, the prediction of "Lipinski's rule of five" showed that most target compounds can cross the BBB and have properties that would make them likely orally active compounds in humans. This study suggested that the synthesized cumarin Manich bases with some more structural modifications may be considered as a potential compound to target AChE and BuChE.