AUSTRALIAN JOURNAL OF CHEMISTRY
·
2021
·Vol. 74
·期 8
·607-612
·
IF 1.321
Yingying Chen,Wenxia Liu,Binbin Zhang,Zhiguang Suo,Feifei Xing,Lingyan Feng,Yingying Chen,Wenxia Liu,Binbin Zhang,Zhiguang Suo,Feifei Xing,Lingyan Feng
A water-soluble and sensitive fluorescent probe N,N′-bis[tris-(2-aminoethyl)amine]-3,4,9,10-perylenetetracarboxylic diimide (PTRIS) was synthesized and, in combination with polydopamine (PDA), utilised in the detection of acetylcholinesterase (AChE) activity. PDA is spontaneously polymerized from dopamine (DA) in aerobic and alkaline solutions. The excellent absorption of PDA results in the aggregation of PTRIS around PDA as well as π–π stacking between them, which consequently quenched the fluorescence of PTRIS due to aggregation induced quenching (AIQ) in 9 min. The hydrolysis product of acetylthiocholine (ATCh) catalyzed by AChE, thiocholine (TCh), was proved to inhibit the polymerization of DA, therefore the free monomeric PTRIS retained its strong fluorescence intensity. The fluorescence was switched off and on depending on the activity of AChE. According to the change of fluorescence intensity at 550 nm, the detection limit of AChE was quantified as 0.02 mU mL−1. It was also proved that this probe possessed excellent selectivity for AChE. Tacrine and the organophosphate pesticide diazinon were further evaluated for inhibitor screening. The half-maximal inhibitory concentration value of tacrine and diazinon was calculated to be 1.4 and 1.6 μM respectively, revealing potential applications for inhibition and pesticide detecting.
研究领域:
分析化学
·
生物化学
·
毒理学
✓ 已验证
DOI
高影响因子
MOLECULES
·
2025
·Vol. 30
·期 17
·3489
·
IF 4.6
Xiaohua Wang,Minglan Ma,Yalan Feng,Jian Liu,Gang Wang
A novel series of multifunctional tacrine–quinoline hybrids were designed, synthesized, and evaluated as potential anti-Alzheimer’s agents. These compounds incorporate tacrine for cholinesterase’s inhibition and 8-hydroxyquinoline for metal chelation. Piperazine was selected as a linker to provide conformational flexibility and to create favorable cation–π interactions with residues in the mid-gorge region of AChE, enhancing dual-site binding with AChE to inhibit Aβ aggregation. In vitro studies demonstrated submicromolar inhibitory activity toward both AChE and BuChE, particularly for compounds16e(IC50= 0.10 μM for AChE, 0.043 μM for BuChE) and16h(IC50= 0.21 μM for AChE, 0.10 μM for BuChE). These compounds also exhibited potent inhibition of self-induced Aβ1–42aggregation (16e: 80.5% ± 4.4%, 16h: 93.2% ± 3.9% at 20 μM). Kinetic analyses revealed mixed-type inhibition, suggesting dual binding to both CAS and PAS of AChE. UV–vis spectrometry confirmed the chelation of Cu2+and Zn2+ions by the 8-hydroxyquinoline moiety. These findings highlight the tacrine–quinoline scaffold as a promising platform for the discovery of a multitarget-directed anti-AD drug.
研究领域:
药物化学
·
神经药理学
·
生物有机化学
·
药物设计
·
阿尔茨海默病研究
✓ 已验证
DOI
PubMed
高影响因子
TALANTA
·
2020
·
IF 5.339
Ting Xiao,Shuang Wang,Mengxia Yan,Jianshe Huang,Xiurong Yang
Acetylcholinesterase (AChE) plays an essential role in biological signal transmission, the aberrant expression of which could cause diverse neurodegenerative diseases. Herein, based on the oxidase-like activity of manganese dioxide nanosheets (MnO 2 NSs), we found that MnO 2 NSs could directly oxidize thiamine into intensely fluorescent thiochrome without the need of peroxides. When AChE was introduced, acetylthiocholine could be hydrolyzed to generate thiocholine, which efficiently triggered the reduction of MnO 2 NSs into Mn 2+ , resulting in the decrease of fluorescence. Owing to the inhibiting effect of tacrine to the AChE activity, the decomposition of MnO 2 was hindered, thus leading to the fluorescence recovery. According to the above mechanism, we constructed a simple, low-cost, label-free, facile and rapid synthetic fluorescent biosensor for highly sensitive and selective detection of AChE activity and screening of its inhibitor. This biosensor obtained a good linear range from 0.02 to 1 mU/mL and an extremely low detection limit of 15 μU/mL for AChE assay, as well as a sensitive screening for tacrine and an excellent applicability in human serum samples. These results suggested that our proposed method would be potentially applied in monitoring the disease progression.
研究领域:
生物化学
·
纳米技术
·
分析化学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL BIOCHEMISTRY
·
2020
·
IF 2.877
Yingying Chen,Wenxia Liu,Binbin Zhang,Zhiguang Suo,Feifei Xing,Lingyan Feng
A reversible fluorescence probe for acetylcholinesterase activity detection was developed based on water soluble perylene derivative, N,N′-di(2-aspartic acid)-perylene-3,4,9,10-tetracarboxylic diimide (PASP). Based on the photo-induced electron transfer (PET), PASP fluorescence in aqueous is quenched after combining with copper ions (Cu 2+ ). Acetylcholinesterase (AChE) is well known to catalyze the hydrolysis of acetylcholine (ATCh) to produce thiocholine, whose affinity is strong enough to capture Cu 2+ by thiol (-SH) group from the complex PASP-Cu, resulting in the fluorescence signal of PASP recovers up to 90%. This optical switch is highly sensitive depended on the coordination and dissociation between PASP and Cu 2+ . We proposed its application for AChE activity detection, as well as its inhibitor screening. According to the change of fluorescence intensity, quantifying the detection limit of AChE was 1.78 mU·mL −1 . Classical inhibitors, tacrine and organophosphate pesticide diazinon, were further evaluated for drug screening. The IC 50 value of tacrine was calculated to be 0.43 μM, and the detection limit of diazinon was 0.22 μM. Both of these performances were much better than previous results, revealing our probe is sensitive and reversible for screening applications.
研究领域:
生物化学
·
分析化学
·
分子生物学
·
药物发现
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF ANALYTICAL CHEMISTRY
·
2021
·
IF 1.134
Guo-Ying CHEN,Hao ZHANG,Cong-Peng ZHAO,Chun-Yan ZHANG,Yuan WANG,Hua CHEN,Feng-Qing YANG
In this study, a capillary electrophoresis-based online immobilized acetylcholinesterase (AChE) microreactor was developed for the determination of organophosphorus pesticide (OPs) residues in six fruit and vegetable juice samples. AChE was immobilized on the inner wall at the inlet of the capillary via polydopamine (PDA) coating. The immobilized AChE activity and other kinetic parameters were evaluated by measuring the peak area of the product (thiocholine). The value of Michaelis-Menten constant ( K m ) was determined to be 3.11 mM, and the half-maximal inhibitory concentration (IC 50 ) and inhibition constant ( K i ) of tacrine on immobilized AChE were measured to be 0.46 μM and 0.27 μM, respectively. The activity of the immobilized AChE remained more than 85.0% of its initial immobilized enzyme activity after 30 runs. Then, the developed strategy was successfully applied to detect the acephate in six fruit and vegetable juice samples (apple, pear, peach, tomato, cucumber and lettuce juice) with a limit of detection (LOD) of 11.0 ng/mL. Results show that the recovery of spiked samples are in the range of 86.0-96.0% with RSD of less than 5.7%. Therefore, the proposed method is capable of achieving rapid analysis of acephate with simple operation when there are no other types of OPs in the real samples.
研究领域:
分析化学
·
环境科学
·
食品科学
✓ 已验证
产品关联
DOI
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
·
药理学
·
神经科学
✓ 已验证
DOI
PubMed
高影响因子
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