Future Medicinal Chemistry
·
2021
·Vol. 13
·期 13
·
IF 3.808
Xin Lu,Yijun Liu,Nan Qin,Hongyu Yang,Yuting Qiao,Xueyang Jiang,Yao Chen,Feng Feng,Wenyuan Liu,You Zhou,Haopeng Sun
Background: Alzheimer's disease is a multifactorial neurological disorder seen in elderly people. Loss of cholinergic transmission and unbalanced tryptophan metabolism kynurenine pathway have been demonstrated in neuropsychiatric diseases. Methods & results: Among the two series of synthesized compounds, compounds 5c and 5h were identified as effective dual BChE/IDO1 inhibitors, with well-balanced micromolar activity. Compounds 5c and 5h exhibited promising ability to ameliorate behavioral impairment by Morris water maze. The safety of miconazole analogs was also validated by PC12 and SH-SY5Y cell lines. Conclusion: These results highlight the ability of 5c and 5h to treat Alzheimer's disease.
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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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
Future Medicinal Chemistry
·
2026
·
IF 3.3
Ziyao Lu,Qinghong Liao,Yuetong Duan,Kaixuan Wang,Siyu He,Weiping Lyu,Xuehong Chen,Qi Li
Objective This study aims to investigate whether butyrylcholinesterase (BChE) inhibitor QY-54 can be used to treat glioblastoma (GBM) and exert a neuroprotective profile.Methods At the cellular level, the effects of QY-54 on the proliferation, invasion, and migration of GBM cells from different species were investigated. At the animal level, the safety of QY-54 in normal mice, its anti-tumor effects in GBM mice, and its effects on cognition protective function were examined.Results At the cellular level, QY-54 exhibited significant inhibitory effects on the proliferation, migration, and invasion of GBM cells derived from different species. At the animal level, QY-54 showed low toxicity in normal mice. Moreover, it significantly inhibited GBM tumor growth, promoted tumor cell apoptosis, suppressed neuroinflammation, protected neurons, and improved the general condition and cognitive function of GBM mice. In Western blot experiments, QY-54 upregulated c-jun N-terminal kinase (JNK) levels to exert an inhibitory effect on glioma.Conclusion QY-54 exhibits dual effects of anti-glioblastoma and cognitive improvement, by inhibiting BChE and activating the JNK signaling pathway. QY-54 is a highly promising drug for the treatment of glioblastoma with neuroprotective profile.
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Shuai Qin,Yujia Ren,Xuxin Yan,Juan Wang,Hai Yang,Xuemei Zhuang,Rong Wang,Shaojun Dong,Daoqing Fan
The accurate analysis and programmed regulation of butyrylcholinesterase (BChE) activity are of paramount significance for many normal physiological activities and disease diagnosis. Nevertheless, there still exist non-negligible drawbacks in previous works, such as the tedious synthesis of frequently used hybridized/doped nanozymes, unsatisfactory accuracy/reliability and adaptability induced by limited output channels, and inferior point-of-care sensing ability. Therefore, development of versatile multimodal biosensors based on cost-effective single-component nanozymes for portable analysis of BChE, intelligent screening of inhibitors, and potential disease diagnosis are urgently needed yet still challenging. To break the above obstacles, herein, taking MnSiO3 nanoparticles with superior OXD-like activity as representative economical single-component nanozymes, we achieved the efficient catalytic oxidation toward a series of optical substrates under broad pH ranges. Collaborative results of experiments and density functional theory calculations elucidated the detailed catalytic mechanism of the MnSiO3 nanozyme. By exploiting the rational natural enzyme/nanozyme tandem catalysis, we constructed a versatile colorimetric–photothermal–fluorescent–RGB quadri-modal platform with flexible-concentration adaptability and realized the portable analysis of BChE in real samples, accompanied by excellent selectivity and competitive LODs. More surprisingly, the clinical diagnosis of patients with aberrant hepatocyte function was validly performed via XNOR-logic-assisted multimodal synergistic validation. Furthermore, taking advantage of the unique interaction between BChE and inhibitors, we fabricated concatenated logic circuits with multichannel outputs and achieved the intelligent logical identification of typical inhibitor drugs. This work not only represented an innovative protocol of multimodal biosensors based on economical and high-performance nanozyme but also enlightened unique horizons for logic-encoded smart analysis of drugs and clinical diagnostics.
研究领域:
生物医学工程
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分子诊断学
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纳米医学
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酶学
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转化医学
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药物代谢
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智能传感
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产品关联
DOI
PubMed
高影响因子
PHYTOCHEMISTRY
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2020
·
IF 3.044
Cai-Ping Yao,Jing Li,Jian-Feng Liu,Zhen-Xing Zou,Feng-Hua Kang,Xiao-Min Li,Dai Li,Kang-Ping Xu,Ping-Sheng Xu,Gui-Shan Tan
Seven undescribed C 27 steroidal glycosides , Seladelicatulasine A–G, including six cholestanol glycosides and one spirostanol glycoside, were isolated from Selaginella delicatula. Their structures were elucidated by 1D/2D NMR spectra and HRESIMS analyses. The absolute configurations of the sugars were determined by enzymatic hydrolysis and GC/MS analyses. These cholestanol glycosides were isolated from the family Selaginellaceae for the first time. Seladelicatulasine F is characterized as a rare B-5,6-secosteroid. In addition, all the compounds were evaluated for their inhibitory activities against cholinesterase (AChE/BChE) and monoamine oxidase (MAO-A/MAO-B). These steroidal glycosides displayed selective inhibition activities on cholinesterase. Seladelicatulasine A, B and E inhibited the AChE activity with IC 50 values of 0.31, 0.09, and 0.04 μ M, respectively. Seladelicatulasine A and F showed the strongest inhibition activity on BChE with IC 50 values of 0.37 and 0.65 μ M, respectively.
研究领域:
药用植物学
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天然产物化学
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生物化学
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神经药理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Chang Xu,Xiao Yu,Guiyang Wang,Shiqing You,Linlin Zhu,Ying Liu,Nuan Zhang,Zhengdong Wang,Bin Liu,Wei Zhang
The butyrylcholinesterase (BChE) is an attractive target for treating Alzheimer's disease. In this study, we report the discovery of five new monoterpene indole alkaloids (MIAs) along with three known analogues from Uncaria sessilifructus Roxb. as BChE inhibitors using affinity ultrafiltration based metabolomic profiling directed isolation strategy. Their structures were well identified through comprehensive spectroscopic and chiroptical analyses. Compounds 1 – 2 featured unique glycosidic linkages with 1, 3-dioxane structure. All the compounds exhibited BChE inhibitory bioactivity without any cytotoxic effects. Enzymatic kinetic and molecular docking analyses of compounds 1 and 6 demonstrated their inhibiting mechanisms and binding patterns to BChE. These findings provide a valuable workflow for efficiently screening ligands that bind to proteins, and scientific recognition in the discovery of BChE inhibitors for treating neurodegenerative disorders.
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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植物化学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
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
MICROCHIMICA ACTA
·
2021
·Vol. 188
·期 11
·1-8
·
IF 5.833
Ma Jinzhu,Ma Lili,Cao Lili,Miao Yuming,Dong Jiangxue,Shi Yu-e,Wang Zhenguang
Butyrylcholinesterase (BChE) is an important indicator for clinical diagnosis of liver dysfunction, organophosphate toxicity, and poststroke dementia. Point-of-care testing (POCT) of BChE activity is still a challenge, which is a critical requirement for the modern clinical diagnose. A portable photothermal BChE assay is proposed through modulating the photothermal effects of Cu 2 O nanoparticles. BChE can catalyze the decomposition of butyrylcholine, producing thiocholine, which further reduce and coordinate with CuO on surface of Cu 2 O nanoparticle. This leads to higher efficiency of formation of Cu 9 S 8 nanoparticles, through the reaction between Cu 2 O nanoparticle and NaHS, together with the promotion of photothermal conversion efficiency from 3.1 to 59.0%, under the excitation of 1064 nm laser radiation. An excellent linear relationship between the temperature change and the logarithm of BChE concentration is obtained in the range 1.0 to 7.5 U/mL, with a limit of detection of 0.076 U/mL. In addition, the portable photothermal assay shows strong detection robustness, which endows the accurate detection of BChE in human serum, together with the screening and quantification of organophosphorus pesticides. Such a simple, sensitive, and robust assay shows great potential for the applications to clinical BChE detection and brings a new horizon for the development of temperature based POCT.
研究领域:
临床诊断
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纳米技术
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生物化学
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医疗器械
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分析化学
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产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2025
·
IF 5.4
Xiabin Chen,Xiaoxuan Li,Huan Liu,Jianzhuang Yao,Yishuang Li,Hualing Li,Zelin Wu,Yun Zhang,Tingjun Hou,Jiye Wang,Shurong Hou
Abnormal activity level of human butyrylcholinesterase (BChE) was detected in patients with cardiovascular disease and neurodegenerative disorders, however, the specific role of BChE in the pathology of these diseases are not known yet. Homocysteine thiolactone (HTL) is a toxic thioester metabolite of homocysteine in conditions of hyperhomocysteinemia (HHcy). Experimental evidences suggest that HTL and resultant N-Hcy proteins that disrupt normal protein function, are associated with the pathology of HHcy-related complications such as cardiovascular diseases. Given the abundance of BChE in the blood and its esterase capacity, it is worthy to investigate the hydrolytic ability of BChE and its genetic polymorphism effects towards the endogenous toxic HTL in order to delineate its function in the complex disease network. In this study, human BChE and acetylcholinesterase (AChE) were examined for their ability in HTL hydrolysis, and BChE demonstrates higher catalytic efficiency than reported serum paraoxonase 1 (PON1). Furthermore, the catalytic mechanism uncovered by Quantum mechanics/Molecular mechanics (QM/MM) molecular dynamics (MD) method helps to understand and substantiate the function of BChE in HTL metabolism. Six frequent BChE nonsynonymous coding single nucleotide polymorphisms (SNPs) variants were recombinantly produced and their catalytic activity was assessed. Differential catalytic efficiency toward HTL was observed among these variants, suggesting their distinct metabolic capability in vivo . These findings highlight the potential protection role of BChE against HTL-induced toxicity, and pave a way for future investigation into BChE’s contribution in HTL metabolism and the possible correlation between specific BChE SNPs and susceptibility for developing HTL-associated diseases.
研究领域:
生物化学
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分子生物学
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酶学
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结构生物学
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遗传学
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心血管研究
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神经科学
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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）