SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2024
·
IF 4.3
Xiujuan Huang,Yuanyuan Cheng,Qi Zhou,Yifeng Tu,Jilin Yan
Acetylcholinesterase (AChE) is an important enzyme in the central and peripheral nervous system that regulates the balance of the neurotransmitter acetylcholine. In this work, a simple, selective and sensitive fluorescence assay was developed toward AChE activity. A conventional AChE substrate acetylthiocholine iodide (ATCI) was applied. Instead directly rendering a signaling, it was found that free iodide ions was released during the enzymatic hydrolysis of ATCI. These ions further catalyzed the oxidation of non-emissive o-phenylenediamine (OPD) into a fluorescent product. This gave a response differed from frequently-adopted sulfhydryl- -based signals and thus minimized related interferences. All materials included in this process were directly available and no additional syntheses were required. Due to the extra iodide-based catalysis included, this scheme was capable of providing a sensitive response toward AChE in the range of 0.01–8 U/L, with a limit of detection at 0.006 U/L. This method was further extended onto chlorpyrifos as an exemplary AChE inhibitor, with a detection down to 3 pM.
研究领域:
分析化学
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生物化学
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酶学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF ENVIRONMENTAL ANALYTICAL CHEMISTRY
·
2023
·
IF 2.6
Lili Miao,Zheng Li,Yu Chen,Yiming Gao,Junwei Di
A sensitive photoelectrochemical biosensor was constructed for the detection of chlorpyrifos. The sensor was prepared on indium tin oxide (ITO) electrode using photoelectric material bismuth vanadate (BiVO4) and acetylcholinesterase (AChE). It is found that the photocurrent of ITO/BiVO4 electrode was largely dependent on its treatment temperature. The highest anodic photocurrent response of the ITO/BiVO4 photoelectrode was obtained after the treatment at 300°C. The thiocholine, produced in the catalytic reaction at ITO/BiVO4/AChE electrode surface, can greatly enhanced the anodic photocurrent. In addition, the adsorption of chlorpyrifos on the surface of the AChE caused a decrease in the intensity of the photocurrent. Under the optimisation of experimental conditions, the decrease of the photocurrent showed a good linear range from 1 pM to 10 nM under irradiation of visible light. The detection limit is calculated as 0.25 pM with a 10% inhibition rate. The ITO/BiVO4/AChE photoelectrode exhibited high sensitivity, acceptable stability and good reproducibility. The biosensor can be provided to the potential applications for detection of pesticide residues in food.
研究领域:
分析化学
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环境科学
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生物传感器
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农药残留分析
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产品关联
DOI
高影响因子
TALANTA
·
2022
·
IF 6.556
Feng Zhang,Sihui Li,Chao Liu,Kun Fang,Yongmei Jiang,Jianyong Zhang,Jie Lan,Lei Zhu,Hanqing Pang,Gang Wang
Insufficient acetylcholine (ACh) can cause cognitive and memory dysfunction, clinically known as, Alzheimer's disease (AD). Acetylcholinesterase (AChE) can hydrolyze ACh into acetic acid and inactivate choline . Therefore, inhibiting the activity of AChE would help to improve the effectiveness of AD treatment . Currently, the methods for rapid screening of AChE inhibitors are limited. This study reports the application of AChE-immobilized magnetic nanoparticles as a drug screening tool to screen AChE inhibitors for natural products . First, AChE was immobilized on a surface of amino-modified magnetic nanoparticles using covalent binding and the AChE concentration, and the pH as well as time was optimized to obtain the maximum enzyme immobilization yield (61.4 μg/mg), and the kinetic model indicated that AChE-immobilized magnetic nanoparticles and the substrate had the high affinity and specificity. Then, a ligand fishing experiment was carried out using a mixed model of tacrine (an inhibitor of AChE) and caffeic acid (a non-inhibitor of AChE) to verify the specificity of the immobilized AChE, and the conditions for ligand fishing were further optimized. Finally, the optimized immobilized AChE was combined with UPLC-MS to screen for AChE inhibitors in Selaginella doederleinii Hieron extracts. Four compounds were confirmed to be potent AChE inhibitors. Among the four compounds, amentoflavone had a stronger AChE inhibitory effect than tacrine (positive control) with an IC 50 of 0.73 ± 0.009 μmol/L. The results showed that AChE-functionalized magnetic nanoparticles can be used in the discovery of target drugs from complex matrices.
研究领域:
药理学
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纳米技术
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分析化学
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神经科学
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2022
·
IF 6.556
Jia Liu,Rui Ma,Wei Ha,Hai-Xia Zhang,Yan-Ping Shi
The inhibition of acetylcholinesterase (AChE) from decomposing acetylcholine (ACh) is regarded as a common therapeutic strategy for Alzheimer's disease (AD). Screening AChE inhibitors is of great significance for AD treatment . In this work, AChE was physically absorbed on the synthesized MnO 2 -ZIF-67 through electrostatic interaction for the first time, and the fabricated MnO 2 -ZIF-67 immobilized AChE coupled with capillary electrophoresis (CE) was applied to screening AChE inhibitor. The established MnO 2 -ZIF-67 immobilized AChE with excellent pH, thermal and organic solvents tolerance stability was evaluated by Ellman's method. Huperzine A was used as model inhibitor to investigate the inhibition kinetics of the immobilized AChE, which possess the feasibility and applicability for its inhibitor screening. The screening mechanism of AChE inhibitor was based on the Ellman's method and measured by the changes of 5-thio-2-nitrobenzoic acid (TNB), which was produced by the reaction of thiocholine (TCh) with 5,5-dithiobis-(2-nitrobenzoic acid) (DTNB). Benefiting from the advantages of convenience and high sensitivity, the proposed platform was employed to screen AChE inhibitors from 11 compounds isolated from Inula macrophylla , and macrophyllic acid A (compound 1 ), dibutyl phthalate (compound 2 ) exhibited strong AChE inhibitory activity. Thus, this work not only provides a promising platform for monitoring AChE activity, but also holds great potential for the further exploration of active components with AChE inhibitory activity from Inula macrophylla .
研究领域:
药学
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分析化学
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神经科学
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药理学
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植物化学
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产品关联
DOI
高影响因子
ARCHIV DER PHARMAZIE
·
2024
·Vol. 357
·期 5
·2300693
·
IF 4.3
Jingfang Zhai,Canhua Hao,Xiaojing Wang,Yuexing Cao,Yinbo Pan,Min Zhou,Jie Sun,Chuanyou Li
Aβ 1−42 and acetylcholinesterase (AChE) are two key therapeutic targets for Alzheimer's disease (AD). The purpose of this study is to develop a dual-target inhibitor that inhibits both of these targets by fusing the chemical structure of baicalein and donepezil. Among them, we modified the structure of baicalein to arylcoumarin, synthesized three kinds of structural compounds, and evaluated their biological activities. The results showed that compound 3b had the strongest inhibitory effect on AChE (IC 50 = 0.05 ± 0.02 µM), which was better than those of donepezil and baicalein. In addition, compound 3b has a strong ability to inhibit the aggregation of Aβ 1−42 and protect nerve cells, and it can also penetrate the blood–brain barrier well. Using a zebrafish behavioral analyzer test, it was found that compound 3b can alleviate the behavioral effects of AlCl 3 -induced zebrafish larval movement retardation, which has a certain guiding significance for simulating the movement disorders of AD patients. In summary, compound 3b is expected to become a multifunctional agent for treating and alleviating the symptoms of AD patients.
研究领域:
药理学
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神经科学
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药物设计
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生物化学
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DOI
高影响因子
ANALYTICA CHIMICA ACTA
·
2020
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IF 5.977
Liping Zhao,Ge Yang,Linsen Li,Chao Zhu,Yao Ma,Feng Qu
Construction of new enzyme reactor based on aptamer functionalized magnetic nanoparticles conjugated organic framework (COF) for acetylcholinesterase immobilization has been an enabling endeavor in this work. The aptamer against acetylcholinesterase was selected through a method based on capillary electrophoresis in one round. A new magnetic COF material rich of carboxyl groups was firstly synthesized, and its surface was then modified with the selected aptamer through covalently linking. Acetylcholinesterase was immobilized to fabricate the enzyme reactor Fe 3 O 4 @COF-Apt-AChE through the high affinity and specificity with its binding aptamer. The as constructed enzyme reactor was comprehensively characterized and the key factors that affected its catalysis efficiency were investigated in detail. Owing to the surface modification of the magnetic COF materials by aptamer for acetylcholinesterase immobilization, the immobilized enzyme exhibited improved substrates affinity. What’s more, good reusability (more than 8 times) and prolonged stability (enzyme activity still kept at 90% after 42 days) were also achieved. Finally, the enzyme reactor could be applied in AChE inhibitors screening, which expanded its application capability. The proposed protocol not only paves a new way for fabrication of novel aptamer functionalized magnetic COF materials as enzyme reactors, but also indicates a broadened application of the integration of aptamer and its enzyme.
研究领域:
纳米技术
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生物化学
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酶工程
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材料科学
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分析化学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2017
·
IF 3.671
Ke-Lin Chen,Ling Gan,Zhen-Hua Wu,Jin-Fang Qin,Wen-Xia Liao,Huang Tang
A series of 4- substituted sampangine derivatives (4-aminoalkylaminosampangine Ar–NH(CH 2 ) n NR 1 R 2 ) has been designed, synthesized, and tested for their ability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and β-myloid (Aβ) aggregation. The synthetic compounds exhibited high AChE inhibitory activity and a significant in vitro inhibitory potency toward the self-induced Aβ aggregation. While, treatment of SH-SY5Y cells overexpressing the Swedish mutant form of human β-amyloid precursor protein (APPsw) with derivatives was associated with significant reduction of Aβ42 secretion levels. Moreover, most of the synthetic compounds were predicted to be able to cross the blood-brain barrier (BBB) to reach their targets in the central nervous system (CNS) according to a parallel artificial membrane permeation assay for BBB. The result encourages us to study this class of compounds thoroughly and systematically.
研究领域:
药理学
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神经科学
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化学
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DOI
PubMed
高影响因子
ACS Omega
·
2021
·
IF 3.512
Lin-Xi Wan,Yong-Qi Zhen,Zhen-Xiang He,Yang Zhang,Lan Zhang,Xiaohuan Li,Feng Gao,Xian-Li Zhou
A new series of N-aryltacrine derivatives were designed and synthesized as cholinesterase inhibitors by the late-stage modification of tacrine, using the palladium-catalyzed Buchwald–Hartwig cross-coupling reaction. In vitro inhibition assay against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) demonstrated that most of the synthesized compounds had potent AChE inhibitory activity with negative inhibition of BuChE. Among them, N-(4-(trifluoromethyl)phenyl)-tacrine (3g) and N-(4-methoxypyridin-2-yl)-tacrine (3o) showed the most potent activity against AChE (IC50 values of 1.77 and 1.48 μM, respectively). The anti-AChE activity of 3g and 3o was 3.5 times more than that of tacrine (IC50 value of 5.16 μM). Compound 3o also displayed anti-BuChE activity with an IC50 value of 19.00 μM. Cell-based assays against HepG2 and SH-SY5Y cell lines revealed that 3o had significantly lower hepatotoxicity compared to tacrine, with additional neuroprotective activity against H2O2-induced damage in SH-SY5Y cells. The advantages including synthetic accessibility, high potency, low toxicity, and adjunctive neuroprotective activity make compound 3o a new promising multifunctional candidate for the treatment of Alzheimer’s disease.
研究领域:
药物化学
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药理学
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神经科学
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DOI
PubMed
高影响因子
PLoS One
·
2024
·Vol. 19
·期 1
·e0297434
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IF 2.9
Haiyun Jiang,Li Kong,Hongguang Tang,Zhenzhen Wang,Caiping Liu,Jianhui Zhang,Yuxin Chen,Jinyang Shen,Yue Zhou
This study aimed to obtain a high yield and purity of Sargassum pallidum polyphenol extracts (SPPE) and study its enzyme activity. Fresh Sargassum pallidum seaweed was selected for optimization of ultrasound-assisted extraction (UAE) conditions and purification conditions using macroporous resin and Sephadex LH20 to obtain SPPE. The SPPE was characterized using UPLC-QTOF-MS/MS and α-amylase, α-glucosidase, tyrosinase, and AchE inhibitory activity were determined. The maximum extraction rate of SPPE was 7.56 mg GAE/g and the polyphenol purity reached 70.5% after macroporous resin and Sephadex LH-20 purification. A total of 50 compounds were identified by UPLC-QTOF-MS/MS. The IC 50 values of SPPE were 334.9 μg/mL, 6.290 μg /mL, 0.834 mg /mL and 0.6538 mg /mL for α-amylase, α-glucosidase, tyrosinase and AchE, respectively. Molecular docking technology further revealed the effects of SPPE on the above enzymes. This study provided information on the potential hypoglycemic, whitening and anti-Alzheimer’s disease biological activities of SPPE, which had guiding significance for the purification and development of other seaweed polyphenols.
研究领域:
海洋生物学
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植物化学
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酶学
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药学
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产品关联
DOI
PubMed
高影响因子
ANALYST
·
2020
·Vol. 145
·期 24
·7849-7857
·
IF 3.978
Chang Liu,Chunyu Huang,Ruixue Ma,Wanying Zhai,Jingjing Deng,Tianshu Zhou
This work demonstrates a new strategy for sensing cerebrospinal acetylcholinesterase (AChE) as a cholinergic biomarker for brain dysfunction based on graphene quantum dot (GQD)-functionalized lanthanide infinite coordination polymer (Ln-ICP) nanoparticles. The ICPs used in this work were comprised of two components, i.e. a supramolecular Ln-ICP host formed by the coordination between the GMP ligand and central metal ion Tb3+, and guest GQDs with abundant functional groups, which were utilized as antenna ligands to further sensitize the fluorescence of Tb/GMP. Upon excitation at 300 nm, the obtained GQD@Tb/GMP ICP nanoparticles exhibited enhanced green fluorescence from Tb/GMP. With the addition of Cu2+, the competitive coordination between Cu2+ and GQDs weakened the antenna effect, leading to a decrease in the fluorescence of GQD@Tb/GMP ICPs. However, in the presence of thiocholine (TCh), a thiol-containing compound hydrolyzed from acetylthiocholine (ATCh) by AChE, a stronger coordination interaction between Cu2+ and TCh occurred, resulting in the restoration of the fluorescence of GQD@Tb/GMP ICPs. Using the method established herein, the cerebrospinal AChE fluctuation of rats with acute organophosphorus pesticide (OP) poisoning or chronic Alzheimer's disease (AD) could be monitored. This study essentially provides a novel approach to realize the direct monitoring of a biomarker for brain dysfunction by regulating the competitive coordination interaction reversibly, which is critical in the early diagnosis and therapy of brain diseases.
研究领域:
纳米技术
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生物化学
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神经科学
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分析化学
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医学诊断
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产品关联
DOI
PubMed
高影响因子
INORGANIC CHEMISTRY
·
2023
·
IF 4.6
Yinhui Yi,Xun Zhou,Diyan Liao,Jieling Hou,Hongde Liu,Gangbing Zhu
The sensitive detection of acetylcholinesterase (AChE) and organophosphorus pesticides (OPs) is very important for the protection of human health. Herein, a hybrid material, Pt NPs/Fe-MOF, consisting of a metal–organic framework (MIL-88B-NH2, Fe-MOF) decorated with platinum nanoparticles (Pt NPs), was prepared first and exhibited remarkably improved and excellent peroxidase-mimicking activity compared to the Fe-MOF material resulting from the synergistic catalysis effect between Fe-MOF and Pt NPs, which can effectively catalyze 3,3′,5,5′-tetramethylbenzidine (TMB) oxidation to generate a blue product (oxidized TMB, oxTMB). Interestingly, in the presence of AChE and acetylcholinesterase, the peroxidase-mimicking activity from Pt NPs/Fe-MOF was inhibited obviously, and thus, a colorimetric sensing platform for AChE can be constructed; more importantly, after the addition of OPs, this nanozyme activity can be recovered, inducing the further successful construction of a sensitive colorimetric sensing platform for OPs. The related sensing mechanism and condition optimization were studied, and the as-prepared Pt NPs/Fe-MOF nanozyme-based colorimetric method for AChE and OP detection displayed superior analytical performances with wide linearities and low detection limits. Furthermore, the designed method offers satisfactory real application ability. We expect the as-proposed Pt NPs/Fe-MOF nanozyme-based colorimetric sensing platform for AChE and OPs via the enzyme cascade reaction to show great potential application.
研究领域:
分析化学
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纳米技术
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环境科学
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生物技术
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2023
·
IF 3.8
Junjie Wang,Hui Zhou,Yang Li,Yeshu Mu,Jinghua Li,Chen Hong,Wen Luo
A novel series of benzo[ cd ]indol-2(1 H )-one-donepezil (BIO-DPZ) hybrids (5a-m, 6a-k) was designed, synthesized and evaluated as cholinesterase inhibitors and living cell imaging agents. These compounds were potent inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Compound 6a exhibited the strongest inhibitory activity against AChE with an IC 50 value of 0.16 μM. Compound 6i had the strongest inhibition of BuChE with an IC 50 value of 5.37 μM. Kinetic and molecular modeling studies showed that 6a bound both catalytic active site and peripheral anionic site of AChE. Compounds 6a and 6i both showed lower SH-SY5Y, HepG2 and HL-7702 cytotoxicity than the mitoxantrone. Promisingly, the most active compound, 6a, was successfully used in living SH-SY5Y cell imaging and had predictable lipophilicity and blood-brain-barrier permeation properties. These hybrids should undergo further systematic study in the treatment of Alzheimer's disease.
研究领域:
药理学
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神经科学
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药物化学
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DOI
高影响因子
危险品化学品经营许可证（带存储）