Methods and Applications in Fluorescence
·
2024
·Vol. 12
·期 2
·025003
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IF 2.4
Conghuan Lin,Huizhi Du
Forsythoside E is one secondary metabolite of Forsythia suspensa (Thunb.) Vahl. In the study, the interactions between forsythoside E and two types of cholinesterases, acetylcholinesterase and butyrylcholinesterase were investigated in the different conditions. Forsythoside E increased the fluorescence intensity of acetylcholinesterase but quenched the fluorescence of butyrylcholinesterase. Aβ25-35 used in the study may not form complexes with cholinesterases, and did not affect the interaction between forsythoside E and cholinesterases. The charged quaternary group of AsCh interacted with the 'anionic' subsite in acetylcholinesterase, which did not affect the interaction between forsythoside E and acetylcholinesterase. The enhancement rate of forsythoside E to acetylcholinesterase fluorescence from high to low was acid solution (pH 6.4), neutral solution (pH 7.4) and alkaline solution (pH 8.0), while the reduction rate of forsythoside E to butyrylcholinesterase fluorescence was in reverse order. Metal ions may interact with cholinesterases, and increased the effects of forsythoside E to cholinesterases fluorescence, in order that Fe3+ was the highest, followed by Cu2+, and Mg2+. A forsythoside E-butyrylcholinesterase complex at stoichiometric ratio of 1:1 was spontaneously formed, and the static quenching was the main quenching mode in the process of forsythoside E binding with butyrylcholinesterase. The K values of two complexes were pretty much the same, suggesting that the interaction between cholinesterases and forsythoside E was almost unaffected by acid–base environment and metal ions. The n numbers of two cholinesterases approximately equaled to one, indicating that there was only one site on each cholinesterase applicable for forsythoside E to bind to.
研究领域:
生物化学
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药理学
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产品关联
DOI
PubMed
高影响因子
Phytochemistry Letters
·
2020
·
IF 1.459
Yang Liu,Xiao-Chang Yao,Jing Li,Zhen-Xing Zou,Chen Xi,Kang-Ping Xu,Feng-Hua Kang,Ping-Sheng Xu,Gui-Shan Tan
Two new unsaturated fatty acid esters ( 1 and 2 ) and five new unsaturated fatty acids ( 4 – 8) , together with two known analogs ( 3 and 9 ) were isolated from the aerial parts of Lycopodiastrum casuarinoides. Their structures were unambiguously elucidated by obtaining extensive spectroscopic data and comparing them with data in the literature. The absolute configurations of 1 and 2 were established by a modified Mosher's method. All compounds were evaluated in vitro for their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compound 8 exhibited the most potent inhibitory activity against AChE with an IC 50 value of 1.16 ± 0.13 μM.
研究领域:
植物化学
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药理学
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DOI
高影响因子
MOLECULES
·
2017
·Vol. 22
·期 7
·1067
·
IF 2.861
Bo Li,Ai-Ling Huang,Yi-Long Zhang,Zeng Li,Hai-Wen Ding,Cheng Huang,Xiao-Ming Meng,Jun Li
In this study we designed and synthesized a series of new hesperetin derivatives on the basis of the structural characteristics of acetylcholinesterase (AChE) dual-site inhibitors. The activity of the novel derivatives was also evaluated. Results showed that the synthesized hesperetin derivatives displayed stronger inhibitory activity against AChE and higher selectivity than butyrylcholine esterase (BuChE) (selectivity index values from 68 to 305). The Lineweaver-Burk plot and molecular docking study showed that these compounds targeted both the peripheral anionic site (PAS) and catalytic active site (CAS) of AChE. The derivatives also showed a potent self-induced β-amyloid (Aβ) aggregation inhibition and a peroxyl radical absorbance activity. Moreover, compound4fsignificantly protected PC12 neurons against H2O2-induced cell death at low concentrations. Cytotoxicity assay showed that the low concentration of the derivatives does not affect the viability of the SH-SY5Y neurons. Thus, these hesperetin derivatives are potential multifunctional agents for further development for the treatment of Alzheimer’s disease.Keywords:hesperetin derivatives;acetylcholinesterase (AChE);butyrylcholine esterase (BuChE);β-amyloid (Aβ);multifunctional
研究领域:
药理学
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神经科学
✓ 已验证
DOI
PubMed
高影响因子
Food & Function
·
2018
·Vol. 9
·期 2
·1173-1178
·
IF 3.289
Zhipeng Yu,Sijia Wu,Wenzhu Zhao,Long Ding,Yue Fan,David Shiuan,Jingbo Liu,Feng Chen
Alzheimer's disease (AD) is a global health issue affecting millions of elderly people worldwide. The aim of the present study was to identify novel anti-AD peptides isolated from albumin. Anti-AD activities of the peptides were evaluated via inhibitory activities on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Furthermore, the potential molecular mechanisms of the KLPGF/AChE were investigated by CDOCKER of Discovery studio 2017. The results revealed that peptide KLPGF could effectively inhibit AChE with an inhibition rate of 61.23% at a concentration of 50 μg mL−1. In addition, the peptide KLPGF came in contact with acylation sites and peripheral anion sites of AChE. The present study demonstrates that the peptide KLPGF could become a potential functional food intervention in AD.
研究领域:
神经生物学
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药理学
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分子生物学
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老年医学
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药物开发
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DOI
高影响因子
METABOLIC BRAIN DISEASE
·
2018
·Vol. 34
·期 1
·173-181
·
IF 2.441
Sun Kaiyue,Bai Yuting,Zhao Rong,Guo Zijiao,Su Xiang,Li Peiqi,Yang Pengyu
The present study was designed to evaluate the effects of matrine (MAT) on scopolamine (SCOP)-induced learning and memory impairment. After successive oral administration of MAT to mice for three days at doses of 0.4, 2, and 10 mg/kg, we assessed improvements in learning and memory and investigated the mechanism of action of SCOP-induced amnesia. Donepezil at a dose of 3 mg/kg was used as a standard memory enhancer. MAT significantly improved SCOP-induced learning and memory impairment in novel object recognition and Y-maze tests at doses of 0.4, 2, and 10 mg/kg. Furthermore, MAT inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities and decreased oxidative stress in the brain, as evidenced by increased total antioxidant capacity, total superoxide dismutase levels, and catalase activities as well as decreased malondialdehyde levels. Additionally, there was a significant negative correlation between the percentage of spontaneous alternation in the Y maze and AChE activity in the cortex and hippocampus. MAT ameliorated SCOP-induced amnesia by the inhibition of both AChE/BuChE activities and oxidative stress. This study provides further evidence to encourage the development of MAT as a drug for the prevention or treatment of Alzheimer’s disease.
研究领域:
神经科学
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药理学
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阿尔茨海默病研究
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产品关联
DOI
PubMed
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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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2023
·
IF 3.8
Yongmei Zhao,Jianwu Lv,Hongli Yu,Kang Huang,Zhihan Du,Wen Luo
A novel series of dictamnine derivatives were synthesized and evaluated as dual inhibitors for cholinesterase and β-amyloid aggregation. These molecules exhibited potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities at the micromolar to sub-micromolar levels. Compound 7k exhibited the strongest inhibitory activity for both AChE and BChE, with IC 50 values of 0.40 μM and 0.63 μM, respectively, improving results from its precursor dictamnine and the commercial inhibitor galanthamine. Kinetic analyses and molecular modeling results indicated a mixed-type inhibition of AChE by compound 7k . In addition, some of the derivatives revealed potent inhibitory activity of AChE induced β-amyloid (Aβ) aggregation. Moreover, 7k did not show toxicity against SH-SY5Y and HL-7702 cells at the tested concentration. Therefore, these dictamnine derivatives, and especially 7k , are suitable candidates for the treatment of Alzheimer's disease and should be further studied.
研究领域:
药物化学
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神经生物学
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有机合成
✓ 已验证
DOI
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
✓ 已验证
DOI
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2022
·
IF 3.841
Jia-bin Su,Wen-long Wu,Chang-E Dong,Shun Yang,Yuan-yuan Feng,Tian Qin,Ke-qi Chen,Jing-jing Qian,Jing-pei Zou,Yu-Han Liu,Shan-ming Liu,Wei-Wei Liu,Da-Hua Shi
Sixteen new 1,3,5-triazine-quinoline derivatives were designed and synthesized and evaluated as cholinesterase inhibitors. The structure of 1,3,5-triazine-quinoline derivatives were confirmed by IR, NMR, HRMS and single crystal X-ray diffraction experiments. Compound 5j had a monoclinic crystal system and P2 1 /c space group. Compound 5k had a monoclinic crystal system and C2/c space group. The cholinesterase inhibitory activity of the synthetic compounds were measured using the colorimetric Ellman's method. Compound 5 g showed best acetylcholinesterase inhibitory activity with IC 50 value of 10.82 μM and butyrylcholinesterase inhibitory activity with IC 50 value of 0.046 μM. Molecular docking showed that the compound 5 g could interacted with the active site of butyrylcholinesterase.
研究领域:
药物化学
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有机化学
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生物化学
✓ 已验证
DOI
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 2
·315
·
IF 4.2
Xiang Cui,Zehong Huang,Shanshan Deng,Yunxia Zhang,Guoyin Li,Lining Wang,Yanru Deng,Changjing Wu
The phytochemical investigation of Cortex Mori Radicis led to the isolation and identification of a new prenylated benzofuranone (1) and four ring-opening derivatives (2–5) named albaphenol A–E, as well as nigranol A (6), together with ten 2-arylbenzofuran derivatives (7–16). The characterization of the structures of the new compounds and the structural revision of nigranol A (6) were conducted using the comprehensive analysis of spectroscopic data (1D/2D NMR, HRESIMS, CD, and XRD). Compounds1–16were tested for their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compounds1and4showed weak BChE-inhibitory activity (IC5045.5 and 61.0 μM); six 2-arylbenzofuran derivatives showed more-potent BChE-inhibitory activity (IC502.5–32.8 μM) than the positive control galantamine (IC5035.3 μM), while being inactive or weakly inhibitory toward AChE. Cathafuran C (14) exhibited the most potent and selective inhibitory activity against BChE in a competitive manner, with a Ki value of 1.7 μM. The structure–activity relationships of the benzofuran-type stilbenes were discussed. Furthermore, molecular docking and dynamic simulations were performed to clarify the interactions of the inhibitor–enzyme complex.
研究领域:
植物化学
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药理学
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神经科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHEMICAL RESEARCH
·
2017
·
IF 0.646
Da-Hua Shi,Zong-Ming Tang,Xiao-Dong Ma,Wei Min,Xiang-Jian Xu,Yu-Wei Liu,Xiao-Kai Song,Wei-Wei Liu,Meng-Qiu Song
Three novel 2-phenylthiazole derivatives were synthesised and characterised by spectroscopic techniques. The structure of the synthesised compounds was unambiguously confirmed by a single-crystal X-ray diffraction analysis of ethyl 2-(4-{[5-(4-benzylpiperidin-1-yl)pentyl]oxy}phenyl)thiazole-4-carboxylate. All of the compounds presented good cholinesterase-inhibition activities and ethyl 2-(4-{[5-(4-benzylpiperidin-1-yl)pentyl]oxy}phenyl)thiazole-4-carboxylate showed the best acetylcholinesterase-inhibition and butyrylcholinesterase-inhibition abilities with IC50 values of 5.19 μM and 5.83 μM. The docking study demonstrated that it could interact with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of acetylcholinesterase and could chelate with metal ions like Cu2+ and Zn2+.
研究领域:
有机化学
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药物化学
·
神经科学
✓ 已验证
DOI
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 6.7
Ziwen Zhang,Shi-Long Zhang,Chengyao Wu,Huan-Huan Li,Liang Zha,Jingbo Shi,Xinhua Liu,Hua-Li Qin,Wenjian Tang
SuFEx click chemistry has been a method for the rapid synthesis of functional molecules with desirable properties. Here, we demonstrated a workflow that allows for in situ synthesis of sulfonamide inhibitors based on SuFEx reaction for high-throughput testing of their cholinesterase activity. According to fragment-based drug discovery (FBDD), sulfonyl fluorides [R–SO 2 F] with moderate activity were identified as fragment hits, rapidly diversified into 102 analogs in SuFEx reactions, and the sulfonamides were directly screened to yield drug-like inhibitors with 70-fold higher potency (IC 50 = 94 nM). Moreover, the improved molecule J8-A34 can ameliorate cognitive function in A β 1−42 -induced mouse model. Since this SuFEx linkage reaction succeeds on picomole scale for direct screening, this methodology can accelerate the development of robust biological probes and drug candidates.
研究领域:
化学
·
药物发现
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神经科学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）