• Bulletin of the Korean Chemical Society
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• 제35권6호
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• pp.1681-1686
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• 2014

A series of hybrid molecules between (${\alpha}$)-lipoic acid (ALA) and 4-amino-1-benzyl piperidines were synthesized and their in vitro cholinesterase (acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)) inhibitory activities were evaluated. Even though the parent compounds did not exhibit any inhibitory activity against cholinesterase (ChE) with the exception of compound 14 ($IC_{50}=255.26{\pm}4.41$ against BuChE), all hybrid molecules demonstrated BuChE inhibitory activity. Some hybrid compounds also displayed AChE inhibitory activity. Specifically, compound 17 was shown to be an effective inhibitor against both AChE ($IC_{50}=1.75{\pm}0.30{\mu}M$) and BuChE ($IC_{50}=5.61{\pm}1.25{\mu}M$) comparable to galantamine ($IC_{50}=1.7{\pm}0.9{\mu}M$ against AChE and $IC_{50}=9.4{\pm}2.5{\mu}M$ against BuChE). Inhibition kinetic studies using compound 17 indicated a mixed inhibition type for AChE and a noncompetitive inhibition type for BuChE. Its binding affinity ($K_i$) values to AChE and BuChE were $3.8{\pm}0.005{\mu}M$ and $7.0{\pm}0.04{\mu}M$, respectively.

• Annals of Clinical Neurophysiology
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• 제23권1호
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• pp.53-55
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• 2021

Congenital myasthenic syndromes (CMSs) are rare genetic disorders characterized by weakness and fatigue resulting from impaired neuromuscular transmission. Genetic testing can confirm the diagnosis for some types of CMS; however, variations in genotype, clinical phenotypes, age at disease onset, and responses to treatment make diagnosis very difficult. Here we present two adult patients who had significant decremental responses in repetitive nerve stimulation testing and multi-minicore pathology, and who responded to treatment with a cholinesterase inhibitor.

• 생물정신의학
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• 제23권2호
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• pp.48-56
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• 2016

Alzheimer's disease (AD) is a neurodegenerative disorder in which neuronal loss causes cognitive decline and other neuropsychiatric problems. It can be diagnosed based on history, examination, and appropriate objective assessments, using standard criteria such as the Diagnostic and Statistical Manual of Mental Disorders or the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA). Brain imaging and biomarkers are making progress in the differential diagnoses among the different disorders. The cholinesterase inhibitors, donepezil, rivastigmine and galantamine and N-methyl-D-aspartate receptors antagonist memantine are approved by the US Food and Drug Administration for AD. Recently some acetylcholinesterase inhibitors gained approval for the treatment of severe AD and became available in a higher dose formulation or a patch formulation. Optimal care in AD is multifactorial and it should include early diagnosis and multidisciplinary care with pharmacological and nonpharmacological interventions including exercise interventions, cognitive interventions and maintenance of social networks.

• Natural Product Sciences
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• 제26권2호
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• pp.165-170
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• 2020

Carica papaya is a medicinal and fruit plant owing biological activities including antioxidant, antiviral, antibacterial and anticancer. The present study aims to investigate the acetyl (AChE) and butyryl (BChE) cholinesterase inhibitory potentials of C. papaya extracts as well as their chemical compositions. The chemical composition of the active extract was identified using a gas chromatography-mass spectrometry (GC-MS). Ellman enzyme inhibition assay showed that the alkaloid-enriched leaf extract of C. papaya possessed significant anti-BChE activity with an enzyme inhibition of 75.9%. GC-MS analysis showed that the alkaloid extract composed mainly the carpaine (64.9%) - a major papaya alkaloid, and some minor constituents such as aliphatic hydrocarbons, terpenes and phenolics. Molecular docking of carpaine revealed that this molecule formed hydrogen bond and hydrophobic interactions with choline binding site and acyl pocket. This study provides some preliminary findings on the potential use of C. papaya leaf as an herbal supplement for the prevention and treatment of Alzheimer's disease.

• International Journal of Industrial Entomology and Biomaterials
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• 제1권1호
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• pp.73-78
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• 2000

We investigated some biochemical properties of acetylcholinesterase (AChE) in the Bombyx mori larval head. 1% Triton X-100 (v/v) was suitable for extracting AChE from the silkworm larval head but 1 M NaCl was not suitable. PAGE analysis showed a single band of AChE that was detected by histochemical staining using acetylthiocholine as a substrate. AChE was also partially purified with Sepharose 6B and DEAE-cellulose column. Finally, the specific activity of partially purified enzyme solution was 7.6. The study on inhibitor specificity indicated that the enzyme under study was a true cholinesterase (ChE) or AChE. AChE activity was maximum at the substrate concentration of $5{\times}10^{-4}$ M and the excess substrate inhibited the AChE activity. The optimal pH and temperature were pH 7.0-9.0 and 30-35$^{\circ}C$.

• 대한의생명과학회지
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• 제13권2호
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• pp.127-133
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• 2007

Heterotrimeric GTP binding proteins (G proteins) mediate signal generated by neurotransmitter and hormones. Among all G proteins, Go is the most abundant in brain but its role in brain is not clearly understood. To determine the function of the alpha subunit of Go (Go$\alpha$), we search for the interacting partner of Go$\alpha$ in brain using yeast two-hybrid system. A resistant to inhibitor of cholinesterase (Ric-8B) was identified as a Go$\alpha$ interacting protein. We confirmed interaction between Go$\alpha$ and Ric-8b employing in vitro affinity binding assay and showed that the Ric-8b increased the function of Go$\alpha$. Our findings indicate that Ric-8b is possible guanine nucleotide exchange factor for Go$\alpha$.

• 한국연초학회지
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• 제20권1호
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• pp.80-86
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• 1998

Changes in activity and classification of esterase isozymes during the tire cycle or Plodia inteipunctella (Hiibner) were investigated by the native polyacrylamide gel electrophoresis. The stage specificity in esterase activity and isozyme pattern was observed throughout the larvalpupal-adult transformation. The activity esterase was highest at the 3-day old adult stage, and the lowest level at the prepupal stage. A total of 12 esterase bands were identified throughout the development, and the bands showing high enzyme activity was observed in the middle part of gel. Twelve esterases on the basis of inhibition by the three types of inhibitors (organophosphates, eserine sulfate and sulfhydryl reagents) were classified into three class, namely, carboxylesterase (CE), arylesterase (ArE) and cholinesterase (ChE), and these classes contained 7, 3 and 2 isozymes, respectively.

• Journal of Chest Surgery
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• 제34권8호
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• pp.634-639
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• 2001

중추성 항콜린성 증후군(Central Anticholinergic Syndrome)은 중추신경계에서 콜린성 신경전달 활성도의 감소로 인하여 다양한 임상 양상을 보이는 질환이다. 이 증후군은 주로 마취시에 사용되는 약제와 연관되며 Physostigmine의 투여 후 증상이 반전되는 것으로 확진된다. 저자들은 뇌혈관 질환의 원인으로 생각되는 난원공 개존증에 대해 개심술을 시행한 후 발생한 중추성 항콜린성 증후군을 Physostigmine의 투여로 확진한 1례에 대하여 보고하는 바이다.

• Molecular & Cellular Toxicology
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• 제2권3호
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• pp.216-221
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• 2006

The cholinesterase-inhibiting organophosphorous (OP) compounds known as nerve agents are highly toxic. The principal toxic mechanism of OP compounds is the inhibition of acethylcholine esterase (AChE) by phosphorylation of its catalytic site. The reversible competitive inhibition of AChE may prevent the subsequent OP intoxication. In this study, three-dimensional quantitative structure-activity relationship (3D-QSAR) was performed to investigate the relationship between the 29 compounds with structural diversity and their bioactivities against AChE. In particular, predictive models were constructed using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The results indicate reasonable model for CoMFA ($q^{2}=0.453,\;r^{2}=0.697$) and CoMSIA ($q^{2}=0.518,\;r^{2}=0.696$). The presence of steric and hydophobic group at naphtyl moiety of the model may lead to the design of improved competitive inhibitors for organophosphorous intoxication.

• 대한한의학회지
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• 제25권4호
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• pp.1-7
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• 2004

Objective : This study was designed to examine the effects of orally administered Prunus persica water extract (PPE), which is used as herbal medicine, for treatment of Yu Xue (stasis of blood) and tacrine on the basal concentration of extracellular acetylcholine in the hippocampus of rats. Methods: To investigate the effects of PPE and tacrine on concentration of extracellular acetylcholine in the hippocampus of rats, the microdialysis technique, under the same experimental conditions, was used. And we used male Wistar rats which were 7 weeks of age and 210-290 g. PPE was extracted with boiling water, and the rats were anesthetized with pentobarbital Na. Their skulls were exposed and a hole was drilled for implantation of a microdialysis probe. In order to increase the recovery of acetylcholine, a probe with a long membrane was used. One day after surgery, the microdialysis probe was perfused with Ringer's solution at a flow rate of 1.5 l/min. The acetylcholine concentration in dialysis samples was measured by high-performance liquid chromatography (HPLC) with electrochemical detection. AChE activity was measured using the radiometric method, as described by Sherman. Results : The comparative effects of PPE and tacrine on hippocampal extracellular acetylcholine concentration was that these cholinesterase inhibitors produced dose-dependent increases in the extracellular acetylcholine concentration. And the effect of PPE and tacrine on rat brain AChE activity was that PPE produced maximal inhibition at 1 h after administration, when AChE activity was 44% of the intact level. AChE activity gradually recovered thereafter, and reached 78% of the intact level at 12 h after administration. Conclusion : In this study, PPE has a potent activity and a long-lasting effect on the central cholinergic system, in terms of the basal concentration of extracellular acetylcholine in the hippocampus and the AChE activity in the brain of rats. And oral administration of PPE increased dose-dependently the basal concentration of extracellular acetylcholine in the hippocampus of rats. PPE may be one of the more useful cholinesterase inhibitors for the treatment of Alzheimer's disease.