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

A highly sensitive, fast and convenient colorimetric assay for acetylcholinesterase (AChE) activity was developed. To do this, phosalone was used to aggregate citrate-coated gold nanoparticles which caused its color to be changed from wine-red to blue. This aggregation was significantly hindered with AChE, due to its preferential reaction with phosalone, and the corresponding color change was probed spectrophotometrically as a function of AChE activity. The ratio of the measured absorbances at the wavelengths of 520 and 650 nm (A520/A650) was found to be linear with the activity of AChE from 0.050 to 1.0 U mL−1 (R2 = 0.9912). A limit of 0.030 U mL−1 for detection of AChE was achieved based on signal to noise ratio of 3. The procedure was successfully applied for determination of AChE in real samples as well as quantitation of phosalone in diverse fields such as food and agricultural industries as well as pharmaceutical, healthcare and environmental affairs.

The present study aims to evaluate the levels of acetyl cholinesterase activity, specific activity, and total protein in blood samples obtained from persons who have received a diagnosis of autism spectrum disorder. Furthermore, the objective of this study is to determine the most favourable parameters for acetyl cholinesterase concentration, substrate concentration, pH level, temperature, and duration. In addition, the present study aims to ascertain the Km and Vmax values of acetyl cholinesterase in blood samples obtained from patients diagnosed with autism spectrum disorder. A complete collection of 100 samples was procured from individuals who have been diagnosed with autism spectrum disorder (ASD). The study's results suggest that persons diagnosed with ASD demonstrate reduced levels of enzyme activity in comparison to the control group. Moreover, the enzymatic activity in individuals with ASD is shown to be significantly elevated compared to the control group. In contrast to the control group, individuals diagnosed with ASD exhibit decreased amounts of total protein. persons with ASD exhibit slight deviations in the thermodynamic characteristics of enzymes, including the activation energy, ΔG, ΔS, Pz, and ΔH*, when compared to persons in the control group.

Alzheimer's disease (AD) is one of the most common neurodegenerative conditions and a major contributor to dementia in the elderly and its prevalence is rising quickly. There are currently 50 million AD sufferers globally, according to the epidemiological data. The most noticeable signs of AD are nearly nonexistent, and they typically include forgetting of recent events. The development of extracellular Amyloid-beta 42 plaques, intracellular hyperphosphorylated Tau tangles, oxidative overload because of mitochondrial malfunction, and genetic abnormalities are just a few of the mechanisms that contribute to AD. Through temporary palliative therapy, which reduces the rate of cognitive damage linked to AD, the current treatment primarily addresses symptoms. In numerous studies, medicinal plants have been linked to potential anti-AD effects. This review aims to explain the underlying pathways of action of various plant-mediated extracts, plant-secondary metabolites, and herbal remedies preparations tested against AD as published in various preclinical and clinical research studies.

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.

Acetylcholinesterase is a promising therapeutic candidate for the treatment of neurodegenerative disorders, acetylcholine dysfunction and other cognitive problems. In the current study, a 3D-QSAR approach was applied to a series of benzimidazole derivatives to reveal the key influencing factors contributing to their acetylcholinesterase inhibition activity and selectivity. The developed two models, CoMFA and CoMSIA, were found to be internally validated using a training set of compounds, and both models demonstrated significant statistical reliability. Contour maps of developed models were employed to examine the main structural characteristics of inhibitors that affected their potency. It was found that electrostatic and hydrophobic interactions are significantly important for improving inhibitory activities, leading to the design of four novel acetylcholinesterase inhibitors. Among the newly designed compounds, compound A1 with the highest predicted activity was subjected to detailed molecular docking and compared to the most active compound. Further, 100 ns molecular dynamics (MD) simulation was conducted to explore the binding modes and conformational modifications throughout the interaction of compound A1 and acetylcholinesterase. The docking and MD simulation findings showed that the newly designed compound A1 remained stable within the active site of the identified acetylcholinesterase receptor, demonstrating its promise as a new potential acetylcholinesterase drug candidate.

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.

In this work, the effect of ligand's length on interaction energy of six oximes, A [2-(hydroxyimino)-N-((1-(2-(2-((hydroxyimino)methyl)-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)methyl)acetamide], B [2-(hydroxyimino)-N-((1-(3-(2-((hydroxyimino)methyl)-1H-imidazol-1-yl)propyl)-1H-1,2,3-triazol-4-yl)methyl)acetamide], C [2-(hydroxyimino)-N-((1-(4-(2-((hydroxyimino)methyl)-1H-imidazol-1-yl)butyl)-1H-1,2,3-triazol-4-yl)methyl)acetamide], D [2-(hydroxyimino)-N-((1-(5-(2-((hydroxyimino)methyl)-1H-imidazol-1-yl)pentyl)-1H-1,2,3-triazol-4-yl)methyl)acetamide], E [2-(hydroxyimino)-N-((1-(6-(2-((hydroxyimino)methyl)-1H-imidazol-1-yl)hexyl)-1H-1,2,3-triazol-4-yl)methyl)acetamide] and F [2-(hydroxyimino)-N-((1-(7-(2-((hydroxyimino)methyl)-1H-imidazol-1-yl)heptyl)-1H-1,2,3-triazol-4-yl)methyl)acetamide] with tabun inhibited acetylcholinesterase (t-AChE) is investigated by using docking methods. The results show that the size of ligand's length, due to changing the position of interactive groups of oximes in active site of enzyme can regulate oxime-enzyme interaction energy for better reactivation of inhibited cholinesterases by oximes. Indeed, increment of oxime-enzyme interaction energy has paradoxical effects both increasing of oxime affinity to t-AChE, and decreasing of the rate of the oxime access to phosphorus atom within tabun binding to the acetylcholinesterase active site. The obtained results show that to design an oxime as a drug, the length of oxime should be chosen in a size that the interaction of oxime and enzyme is neither too weak to couple, nor too strong to limit oxime mobility in reactivation t-AChE after coupling.