PEST MANAGEMENT SCIENCE
·
2014
·Vol. 71
·期 4
·607-615
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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
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昆虫学
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药理学
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天然产物化学
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
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2020
·
IF 4.831
Shaochun Shi,Huibin Wang,Jian Wang,Yvxi Wang,Xiaobian Xue,Zilin Hou,Guo-Dong Yao,Xiao-Xiao Huang,Hongwei Zhao,Qingbo Liu,Shao-Jiang Song
7- O -galloyltricetiflavan (GTF), a natural flavonoid, is known to exert anti-oxidation and neuroprotective activity, which are related to the prevention of Alzheimer’s disease (AD). In this study, three series of GTF hybrids have been designed, synthesized and evaluated as multifunctional agents for treatment AD. The biological assays indicated that most of them showed strong inhibitory effect on self-induced β -amyloid (A β ) aggregation, and a significant ability to inhibit ChEs. Among them, compound A15 exhibited best inhibition of A β aggregation (78.81% at 20 μM), potent AChE inhibitory potencies (IC 50 , 0.56 μM), and compound C4 presented the highest ability to inhibit BuChE (IC 50 , 5.77 μM). Furthermore, kinetic, molecular modeling and molecular dynamics studies revealed that A15 and C4 could interact with the catalytic active site of AChE and BuChE, respectively. In addition, compounds A15 and C4 could cross the blood–brain barrier in vitro. More importantly, A15 and C4 also showed excellent neuroprotective activities against H 2 O 2 -induced human neuroblastoma SH-SY5Y cells damage and nearly no toxicity on SH-SY5Y cells. All of these outstanding in vitro results indicated A15 and C4 as the leading structure worthy of further investigation.
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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产品关联
DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
·
2022
·
IF 6.449
Chuks Fidelis Nwanade,Min Wang,Hongxia Li,Abolfazl Masoudi,Zhijun Yu,Jingze Liu
Plant essential oils (EOs) are usually complex mixtures of volatile compounds, and these compounds can vary in composition as a result of biotic and abiotic factors. Thus, understanding the contribution of the individual compounds particularly their interactions with respect to acaricidal activity is important for the use of EOs as an alternative to synthetic acaricides . Herein, the acaricidal activity of constituents from EOs of cinnamon ( Cinnamomum zeylanicum and Cinnamomum cassia ) against Haemaphysalis longicornis was investigated using the nymphal and adult immersion tests. Among the test compounds, benzyl benzoate showed the highest toxicity against the nymphs (LC 50 = 24.41 µL/mL) and adults (LC 50 = 3.99 µL/mL). All combinations at their sublethal concentration (LC 30 ) exhibited synergy. The binary mixture of benzyl benzoate + cinnamaldehyde presented the highest synergy ratio (3.42) while tertiary mixtures of cinnamaldehyde + eugenol + linalool showed the least synergy ratio (1.20). Enzyme assays revealed that benzyl benzoate significantly inhibited AChE activity ( p < 0.05). The ecotoxicological assessments of benzyl benzoate and cinnamaldehyde indicate likely minimal effects on non-target terrestrial invertebrate, Tenebrio molitor . On the other hand, they were toxic to non-target aquatic species , Daphnia magna . Based on our results, the acaricidal activity of cinnamon EO against H . longicornis may be linked to the content of benzyl benzoate whose presence may be synergistic to the activity of other compounds.
研究领域:
昆虫学
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药理学
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毒理学
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植物科学
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产品关联
DOI
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
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
TALANTA
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2022
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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
Journal of Applied Spectroscopy
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2018
·Vol. 85
·期 3
·437-444
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IF 0.611
Zhao Lingzhi,Zhao Liu,Zhang Chenxiao,Li Yanqi
We demonstrate the utility of 4-chloro-7-nitrobenzofurazan (NBD-Cl), a simple, low-cost probe, for colorimetrically and fluorescently detecting and differentiating similar thiol species, including cysteine, homocysteine, and glutathione, as well as for assaying acetylcholinesterase (AChE) activity. This assay is a potential tool for investigating thiol functions in disease and diagnosis, and for screening AChE inhibitors. We envision that this versatile probe, which is commercially available and inexpensive, will be useful for further elucidating the roles of thiols in biology and also shows applicability for analysis of AChE inhibitors in physiological samples.
研究领域:
分析化学
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生物化学
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分子生物学
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诊断学
✓ 已验证
产品关联
DOI
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
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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
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
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2022
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IF 8.008
Yu Wang,Yu Xue,Qilin Zhao,Shuang Wang,Jian Sun,Xiurong Yang
Alzheimer’s disease (AD) is a common chronic neurodegenerative disease that manifests as cognitive impairment and behavioral deficits and severely threatens the health of the elderly. Acetylcholinesterase (AChE) plays a vital role in biological signaling and is an essential target for the early diagnosis and treatment of AD. Herein, 2D Zn-TCPP(Fe) nanosheets (NSs) employing Zn2+ and Fe-bound tetrakis(4-carboxyphenyl)porphyrin ligands were prepared through a surfactant-assisted synthetic method. The ultrathin two-dimensional (2D) metal–organic framework structures exhibited high peroxidase-like activity, which allowed the catalysis of the H2O2-initiated oxidation of colorless 3,3′,5,5′-tetramethylbenzidine (TMB) to blue oxidized TMB (ox-TMB). Such catalytic performance inspired us to develop a convenient, rapid, and sensitive acetylcholinesterase activity assay, during which AChE can catalyze the substrate acetylthiocholine (ATCh) to produce thiocholine (TCh), and TCh could especially enable the degradation of 2D Zn-TCPP(Fe) NSs accompanied by the reduction of ox-TMB production. Our proposed sensing system exhibited favorable selectivity and sensitivity (LOD of 0.029 mU/mL) and has excellent potential to evaluate AChE activity in human serum samples and to screen AChE inhibitors. This colorimetric assay could provide an alternative pathway for early diagnosis and drug screening of AD, facilitating the development of AD therapy.
研究领域:
神经退行性疾病
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生物化学
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纳米技术
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诊断方法
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药物筛选
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2021
·
IF 3.205
Hui-Peng Song,Hui Zhang,Rui Hu,Hong-He Xiao,Hua Guo,Wei-Hong Yuan,Xin-Tong Han,Xin-Yi Xu,Xin Zhang,Zi-Xuan Ding,Ming-Yue Zhao,Ting-Guo Kang,Hui-Yang Sun,An Chang,Yue-Hua Chen,Ming Xie
Lead compound is an important concept for modern drug discovery. In this study, a new concept of lead chemome and an efficient strategy to discover lead chemome were proposed. Compared with the concept of lead compound, lead chemome can provide not only the starting point for drug development, but also the direction for structure optimization. Two traditional Chinese medicines of Mahonia bealei and Mahonia fortunei were used as examples to illustrate the strategy. Based on natural chromatogram-effect correlation (NCEC), berberine, palmatine and jatrorrhizine were discovered as acetylcholinesterase (AchE) inhibitors. Taking the three compounds as template molecules, a lead chemome consisting of 10 structurally related natural compounds were generated through natural structure-effect correlation (NSEC). In the lead chemome, the IC 50 values of jatrorrhizine, berberine, coptisine, palmatine and epiberberine are at nanomolar level, which are comparable to a widely used drug of galantamine. Pharmacophore modeling shows that the positive ionizable group and aromatic rings are important substructures for AchE inhibition. Molecular docking further shows that pi-cation interaction and pi-pi stacking are critical for compounds to maintain nanomolar IC 50 values. The structure–activity information is helpful for drug design and structure optimization. This work also expanded the traditional understanding of “stem is the medicinal part of Mahonia bealei and Mahonia fortunei ”. Actually, all parts except the leaf of Mahonia bealei exhibited potent AchE-inhibitory activity. This study provides not only a strategy to discover lead chemome for modern drug development, but also a reference for the application of different parts of medicinal plants.
研究领域:
药理学
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中药学
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药物发现
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天然产物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）