ANALYST
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2026
·
IF 3.6
Jun Zhang,Wenzhu Jiang,Zhiping Xu,Lin Zhang
Generally, unstable metal–organic frameworks (MOFs) have been less commonly employed in many applications compared to stable MOFs. However, given the vast number of such unstable MOFs and the diversity of their instability behaviors, exploring their effective utilization is both necessary and significant. Unlike previous reports, this work mainly focused on the specific instability of Cu-BTC towards thiocholine, which was generated through the enzymatic hydrolysis of acetylthiocholine chloride (ATCl) by acetylcholinesterase (AChE). In detail, Cu-BTC exhibited outstanding peroxidase-like activity, efficiently catalyzing the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) into its oxidized form, generating a strong UV–vis absorption peak at 655 nm. Upon the addition of AChE and its substrate ATCl, the substrate was hydrolyzed by AChE to yield thiocholine (TCl), which triggered the disintegration of Cu-BTC, thereby inhibiting TMB oxidation. As expected, based on the thiocholine-induced disintegration of Cu-BTC, the sensor enabled the selective and sensitive visual detection of the AChE inhibitor chlorpyrifos with a low detection limit of 8.95 pM. This method was successfully applied to pesticide analysis in spiked vegetable samples, achieving recoveries ranging from 98.83% to 109.81% with relative standard deviations below 2.57%. The proposed strategy not only provides a simple and visual approach for food safety monitoring but also opens new possibilities for exploiting unstable MOFs as smart sensing platforms.
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BIOELECTROCHEMISTRY
·
2019
·
IF 4.474
Pan Zhang,Tingting Sun,Shengzhong Rong,Dongdong Zeng,Hongwei Yu,Ze Zhang,Dong Chang,Hongzhi Pan
Long-term accumulation of organophosphate pesticides in environment presents a potential hazard to human and animal health. Towards this, a highly sensitive amperometric AChE-biosensor based on conjugated polymer and Ag-rGO-NH 2 nanocomposite has been successfully developed. First, 4, 7-di (furan-2-yl) benzo thiadiazole (FBThF) was electrochemically polymerized on the electrode surface. Then, Ag-rGO-NH 2 nanocomposite and acetylcholinesterase (AChE) are modified on the polymer membrane surface. In this way, a novel amperometric AChE-biosensor was successfully prepared. The as-prepared biosensor possessed excellent conductivity, catalytic activity , and biocompatibility which were attributed to the synergistic effects of poly(FBThF) and Ag-rGO-NH 2 and provided a hydrophilic surface for AChE adhesion. Under optimized conductions, the linear range was 0.099–9.9 μg L −1 with a regression coefficient of 0.9947 for malathion , 0.0206–2.06 μg L −1 with a regression coefficient of 0.9969 for trichlorfon . The detection limit is calculated to be about 0.032 μg L −1 for malathion and 0.001 μg L −1 for trichlorfon (S/N = 3). Moreover, the biosensor exhibited acceptable reproducibility and long-term stability, which makes it possible to provide a novel and promising tool for analysis of organophosphate pesticides.
研究领域:
分析化学
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环境科学
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生物医学工程
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BIOORGANIC CHEMISTRY
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2018
·
IF 3.929
Qi He,Jing Liu,Jin-Shuai Lan,Jiaoli Ding,Yongbing Sun,Yuanying Fang,Neng Jiang,Zunhua Yang,Liyuan Sun,Yi Jin,Sai-Sai Xie
A series of new coumarin-dithiocarbamate hybrids were designed and synthesized as multitarget agents for the treatment of Alzheimer’s disease. Most of them showed potent and clearly selective inhibition towards AChE and MAO-B. Among these compounds, compound 8f demonstrated the most potent inhibition to AChE with IC 50 values of 0.0068 μM and 0.0089 μM for eeAChE and hAChE, respectively. Compound 8g was identified as the most potent inhibitor to hMAO-B, and it is also a good and balanced inhibitor to both hAChE and hMAO-B (0.114 µM for hAChE; 0.101 µM for hMAO-B). Kinetic and molecular modeling studies revealed that 8g was a dual binding site inhibitor for AChE and a competitive inhibitor for MAO-B. Further studies indicated that 8g could penetrate the BBB and exhibit no toxicity on SH-SY5Y neuroblastoma cells. More importantly, 8g did not display any acute toxicity in mice at doses up to 2500 mg/kg and could reverse the cognitive dysfunction of scopolamine-induced AD mice. Overall, these results highlighted 8g as a potential multitarget agent for AD treatment and offered a starting point for design of new multitarget AChE/MAO-B inhibitors based on dithiocarbamate scaffold.
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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JOURNAL OF MEDICINAL CHEMISTRY
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2021
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IF 7.446
Hong Yao,Giuseppe Uras,Pengfei Zhang,Shengtao Xu,Ying Yin,Jie Liu,Shuai Qin,Xinuo Li,Stephanie Allen,Renren Bai,Qi Gong,Haiyan Zhang,Zheying Zhu,Jinyi Xu
Based on a multitarget strategy, a series of novel tacrine–pyrimidone hybrids were identified for the potential treatment of Alzheimer’s disease (AD). Biological evaluation results demonstrated that these hybrids exhibited significant inhibitory activities toward acetylcholinesterase (AChE) and glycogen synthase kinase 3 (GSK-3). The optimal compound 27g possessed excellent dual AChE/GSK-3 inhibition both in terms of potency and equilibrium (AChE: IC50 = 51.1 nM; GSK-3β: IC50 = 89.3 nM) and displayed significant amelioration on cognitive deficits in scopolamine-induced amnesia mice and efficient reduction against phosphorylation of tau protein on Ser-199 and Ser-396 sites in glyceraldehyde (GA)-stimulated differentiated SH-SY5Y cells. Furthermore, compound 27g exhibited eligible pharmacokinetic properties, good kinase selectivity, and moderate neuroprotection against GA-induced reduction in cell viability and neurite damage in SH-SY5Y-derived neurons. The multifunctional profiles of compound 27g suggest that it deserves further investigation as a promising lead for the prospective treatment of AD.
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JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
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2026
·
IF 5.3
Wei Li,Yan Guo,Xiaoli Wang,Chunyan Yang,Jiang Zhu,Zhongcheng Cao
Alzheimer’s disease (AD) still lacks therapies that definitively halt its progression. Dual AChE/MAO-B inhibitors offer a promising strategy to address both symptoms and pathology. Here, we designed and synthesised a series of donepezil-safinamide hybrids. The optimised compound 28c was identified as a potent inhibitor of AChE (IC50 = 1.70 μM) and MAO-B (IC50 = 0.18 μM). Mechanistic studies indicated that 28c acts as a reversible mixed-type inhibitor of AChE and a competitive reversible inhibitor of MAO-B. Molecular docking and molecular dynamic simulations revealed that 28c could strongly and stably bind to MAO-B and AChE mainly through van der Waals interactions. Moreover, compound 28c demonstrated effective blood-brain barrier penetration, exhibited suitable stability in mouse plasma and brain homogenate, and showed a favourable safety profile both in vitro and in vivo. Furthermore, 28c could attenuate AD-related symptoms and exert hippocampal neuroprotection effect in vivo, highlighting its promise as an anti-AD candidate.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Yanwen Zhu,Zhaoliang Hu,Yunen Liu,Tingcai Yan,Ling Liu,Yanqun Wang,Bing Bai
Hydrogen sulfide (H 2 S), or dihydrogen sulfane (H 2 S n ), acts as a signal molecule through the beneficial mechanism of persulfidation, known as the post-translational transformation of cysteine residues to persulfides. We previously reported that Glutathione (GSH) could regulate enzyme activity through S-desulfurization or glutathionylation of residues to generate protein-SG or protein-SSG, releasing H 2 S. However, little is known about the mechanisms by which H 2 S n and GSH affect the disulfide bonds . In this study, we provide direct evidences that H 2 S n and GSH modify the sulfhydryl group on Cys272, which forms disulfide bonds in acetylcholinesterase (AChE), to generate Cys-SSH and Cys-SSG, respectively. Glutathionylation of disulfide is a two-step reaction based on nucleophilic substitution, in which the first C S bond is broken, then the S S bond is broken to release H 2 S. H 2 S n and GSH controlled self-breathing motion in enzyme catalysis by disconnecting specific disulfide bonds and modifying cysteine residues, thereby regulating AChE activity. Here, we elucidated H 2 S n and GSH mechanisms on disulfide in the AChE system and proposed a self-breathing control theory induced by H 2 S n and GSH. These theoretical findings shed light on the biological functions of H 2 S n and GSH on sulfhydryl and disulfide bonds and enrich the theory of enzyme activity regulation.
研究领域:
生物化学
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分子生物学
·
酶学
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SENSORS AND ACTUATORS B-CHEMICAL
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2023
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IF 8.4
Yu Wang,Qilin Zhao,Yu Xue,Donghui Wu,Bing Zhang,Jian Sun,Xiurong Yang
Acetylcholinesterase (AChE) activity and its inhibitor assays play a vital role in the early diagnosis and drug screening of certain diseases. In this work, we for the first time found that the protein-inorganic hybrid nanoflowers (HNFs) [BSA-Cu 3 (PO 4 ) 2 ] exhibits an obvious laccase-like catalytic activity . Further, through the regulation of laccase-mimicking activity, we developed a convenient and original colorimetric tactic for sensitive and selective assaying of acetylcholinesterase (AChE) activity and its inhibitors. Most surprisingly, AChE can catalyze acetylthiocholine (ATCh) into thiocholine (TCh), which could significantly enhance the catalytic activity of BSA-Cu 3 (PO 4 ) 2 HNFs. The enhanced laccase-like activity accelerates the chromogenic reaction between 2,4-dichlorophenol (2,4-DP) and 4-aminoantipyrine (4-AP), and the relevant product exhibits a red color which is owing to the reduction of Cu 2+ in the HNFs to Cu + by TCh. According to the facile signal-on response with clear response mechanism, our method has been successfully applied for the highly sensitive detection of AChE activity with a linear range of 0.25–5 mU/mL, and testing AChE inhibitors , especially obtaining satisfactory results in real samples. It is expected that such facile strategy could pave the way for the potential applications of biometric catalysts in disease diagnosis and environmental monitoring.
研究领域:
生物化学
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医学诊断
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环境监测
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高影响因子
MOLECULES
·
2016
·Vol. 21
·期 2
·132
·
IF 2.465
Zeng Li,Chaoyu Mu,Bin Wang,Juan Jin
This study designed and synthesized a series of new graveoline analogs on the basis of the structural characteristics of acetylcholinesterase (AChE) dual-site inhibitors. The activity of these analogs was also evaluated. Results showed that the synthesized graveoline analogs displayed stronger inhibitory activity against AChE and higher selectivity than butyrylcholine esterase (BuChE) (Selectivity Index from 45 to 486). When the two sites in the graveoline parent ring substituting phenyl and amino terminal had six chemical bonds (n= 3) and the terminal amino was piperidine, compound5cshowed the best activity. Furthermore, the mechanism of action and binding mode were explored by enzyme kinetic simulation, molecular docking, and thioflavin T-based fluorometric assay. Cytotoxicity assay showed that the low concentration of the analogs did not affect the viability of the neurocyte SH-SY5Y.Keywords:graveoline analogs;acetylcholinesterase (AChE);butyrylcholine esterase (BuChE);structure–function relationships (SARs);mechanism
研究领域:
神经科学
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药物化学
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老年医学
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BIOSENSORS & BIOELECTRONICS
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2024
·
IF 10.7
Chen Zhan,Jiahui Zhang,Junxing Hao,Zhihong Liu,Chengguo Hu
A drop-casting method for the scalable construction of a solar cell-type light-addressable photoelectrochemical (PEC) sensor on commercial phenol resin (PR) plates is reported. The sensor was fabricated by laser writing of addressable laser-induced graphene (LIG) electrode arrays on PR plates with ring-disc dual-electrode cell configurations using a 405 nm laser machine. Beneficial from the good hydrophilicity of PR-based LIG and the excellent film formation of bismuth sulfide nanorods (Bi 2 S 3 NRs), uniform Bi 2 S 3 photovoltaic films can be reproducibly deposited onto the LIG disc photoanode array via drop casting modification, which show a sensitive photocurrent response toward thiocholine (TCl) when the ring cathode array was coated with Ag/AgCl. An acetylcholinesterase (AChE)-based PEC biosensor was therefore constructed by a similar drop-casting modification method. The resulting biosensor exhibits good sensitivity toward an AChE inhibitor , i.e., galantamine hydrobromide (GH), with a calibration range of 10–300 μM and a detection limit of 7.33 μM (S/N = 3). Moreover, the biosensor possesses good storage stability, which can achieve the high-throughput screening of AChE inhibitor drugs from traditional Chinese medicines (TCMs). The present work thus demonstrates the promising application of LIG technology in constructing light-addressable PEC sensing devices with high performance and low cost.
研究领域:
生物传感器
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光电化学
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药物筛选
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纳米材料
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电化学
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CHEMICAL PHYSICS LETTERS
·
2026
·
IF 2.9
Wei-Lin Zhu,Lei Meng,Liang Shen
Multifunctional carbon dots from lemon peel (LP-CDs) were synthesized via hydrothermal method. • Toxicity assessment confirmed that LP-CDs were of low toxicity. • LP-CDs reduced apoptosis and alleviated oxidative stress in PC-12 cells caused by hydrogen peroxide. • LP-CDs were found to inhibit AChE activity. • LP-CDs exhibited the ability to mitigate Aβ aggregation. In this study, multifunctional food-derived carbon dots from lemon peel (LP-CDs) were synthesized by a green hydrothermal method for relieving Alzheimer's disease, by inhibiting acetylcholinesterase (AChE) activity, amyloid β-peptide (Aβ) aggregation and alleviating oxidative stress. Firstly, LP-CDs possessed an average particle size of 2.54 nm, and optimal emission and excitation wavelengths of 454 nm and 362 nm. Secondly, LP-CDs demonstrated good antioxidant and AChE inhibitory activities in vitro. Thirdly, through thioflavin T fluorescence analysis and transmission electron microscopy, it was preliminarily confirmed that LP-CDs had potential ability of inhibiting Aβ aggregation. Fourthly, LP-CDs could reduce apoptosis and alleviate oxidative stress in PC-12 cells and reduced malondialdehyde levels in cells. Compared with traditional single target ingredient, LP-CDs are expected to achieve multi-targets synergy with higher bioavailability, which deserves further in vivo study. Download: Download high-res image (224KB) Download: Download full-size image
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PEST MANAGEMENT SCIENCE
·
2014
·Vol. 71
·期 4
·607-615
·
IF 2.743
Yong-Hao Ye,Cong Li,Jun Yang,Liang Ma,Yu Xiao,Jun Hu,Nasir Ahmed Rajput,Cong-Fen Gao,Ying-Ying Zhang,Ming-Hua Wang
BACKGROUND Application of a matrix-immobilised target enzyme for screening inhibitors is widely used in drug development, but there are few studies in insecticide discovery. In this paper, an economical and effective immobilised acetylcholinesterase (AChE) column was prepared using the sol–gel embedment method, which was further combined with high-performance liquid chromatography for screening the AChE inhibitors and insecticidal compounds from complex natural products. RESULTS AChE inhibitory constituents magnolol and honokiol were isolated from the ethanol extract of Magnolia officinalis , with IC 50 values of 0.069 and 0.057 mM respectively. In an in vivo bioassay, magnolol and honokiol showed insecticidal activity against Nilaparvata lugens , with LC 50 values of 0.324 and 0.137 mM, which are comparable with that of commonly used insecticide chlorpyrifos (0.233 mM). Moreover, molecular docking was carried out against a homology model of N. lugens AChE. The complexes showed that magnolol and honokiol placed themselves nicely into the active site of the enzyme and exhibited an interaction energy that was in accordance with our activity profile data. CONCLUSION These results demonstrate that magnolol and honokiol have great applied potential to be developed as natural insecticides, and an immobilised AChE column is very useful as a rapid screening tool for target enzymes towards potent inhibitors. © 2014 Society of Chemical Industry
研究领域:
生物化学
·
昆虫学
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药理学
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天然产物化学
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Marine Drugs
·
2019
·Vol. 17
·期 7
·401
·
IF 3.772
Isabel Gómez-Betancur,Jianping Zhao,Lin Tan,Lina Preciado
Marine organisms are recognized as a source of compounds with interesting biological activities.Vibrio neocaledonicushas been reported on for its high effectiveness against corrosion in metals but it has been little studied for its chemical and biological activities. In this study, four compounds were isolated fromV. neocaledonicus: indole (1); 1H-indole-3-carboxaldehyde (2); 4-hydroxybenzaldehyde (3) and Cyclo (-Pro-Tyr) (4); using a bioassay-guided method, since in a previous study it was found that the ethyl acetate extract was active on the enzymes acetylcholinesterase (AChE), alpha-glucosidase (AG) and xanthine oxidase (XO). The inhibitory activities of the three compounds against AChE, AG and XO was also evaluated. In addition, the enzymatic inhibitory activity of indole to the toxins from the venom ofBothrops asperwas tested. Results showed that indole exhibited strong inhibitory activity to AG (IC50= 18.65 ± 1.1 μM), to AChE, and XO (51.3% and 44.3% at 50 μg/mL, respectively). 1H-indole-3-carboxaldehyde displayed strong activity to XO (IC50= 13.36 ± 0.39 μM). 4-hydroxybenzaldehyde showed moderate activity to XO (50.75% at 50 μg/mL) and weak activity to AChE (25.7% at 50 μg/mL). Furthermore, indole showed a significant in vitro inhibition to the coagulant effect induced by 1.0 μg of venom. The findings were supported by molecular docking. This is the first comprehensive report on the chemistry ofV. neocaledonicusand the bioactivity of its metabolites.Keywords:Vibrio neocaledonicus;acetylcholinesterase (AChE);alphaglucosidase (AG);xanthine oxidase (XO);indole;bioactive compounds;snake venom
研究领域:
海洋生物学
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药理学
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生物化学
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