• 한국균학회지
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• 제49권2호
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• pp.243-248
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• 2021

본 연구에서는 진균류 유래의 새로운 항치매성 BChE저해물질을 생산할 목적으로 대전광역시 하천에서 분리하여 선별한 비병원성 야생효모들의 무세포추출물들을 제조하여 이들의 BChE 저해활성 측정하였다. 비병원성 야생효모들 중 S. cerevisiae WJSL0113의 무세포추출물이 85.2%의 BChE 저해활성을 보여 최종 선발하였다. 선발 균주의 BChE 저해활성은 시판 주류용 S. cerevisiae과 식용 버섯들의 추출물보다 높은 저해활성을 보였고 선발 균주인 S. cerevisiae WJSL0113을 30℃에서 48시간 배양하였을 때 가장 높은 항치매성 BChE 저해활성을 보였다.

• Natural Product Sciences
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• 제24권2호
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• pp.88-92
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• 2018

The present study was undertaken to investigate the isolated compounds from the stem bark of Garcinia atroviridis as potential cholinesterase inhibitors and the ligand-enzyme interactions of selected bioactive compounds in silico. The in vitro cholinesterase results showed that quercetin (3) was the most active AChE inhibitor ($12.65{\pm}1.57{\mu}g/ml$) while garcinexanthone G (6) was the most active BChE inhibitor ($18.86{\pm}2.41{\mu}g/ml$). It is noteworthy to note that compound 6 was a selective inhibitor with the selectivity index of 11.82. Molecular insight from docking interaction further substantiate that orientation of compound 6 in the catalytic site which enhanced its binding affinity as compared to other xanthones. The nature of protein-ligand interactions of compound 6 is mainly hydrogen bonding, and the hydroxyl group of compound 6 at C-10 is vital in BChE inhibition activity. Therefore, compound 6 is a notable lead for further drug design and development of BChE selective inhibitor.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.165-170
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• 2023

Isolation of the culture broth of a marine-derived Acremonium sp. CNQ-049 guided by HPLC-UV yielded compound 1 (3-phenethyl-2-phenylquinazolin-4(3H)-one), and its inhibitory activities against monoamine oxidases (MAOs), cholinesterases (ChEs), and β-secretase 1 (BACE1) were evaluated. Compound 1 was an effective selective MAO-B inhibitor with an IC₅₀ value of 9.39 µM and a selectivity index (SI) value of 4.26 versus MAO-A. In addition, compound 1 showed a potent selective butyrylcholinesterase (BChE) inhibition with an IC₅₀ value of 7.99 µM and an SI value of 5.01 versus acetylcholinesterase (AChE). However, compound 1 showed weak inhibitions against MAO-A, AChE, and BACE1. The Ki value of compound 1 for MAO-B was 5.22±1.73 µM with competitive inhibition, and the Ki value of compound 1 for BChE was 3.00±1.81 µM with mixed-type inhibition. Inhibitions of MAO-B and BChE by compound 1 were recovered by dialysis experiments. These results suggest that compound 1 is a dual-functional reversible inhibitor of MAO-B and BChE, that can be used as a treatment agent for neurological disorders.

• Bulletin of the Korean Chemical Society
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• 제32권8호
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• pp.2593-2598
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• 2011

Polyphenols (PPs) are known as antioxidant compounds having benign biological activities. In this paper, a series of hybrid molecules between the free or acetyl protected polyphenol compounds were synthesized and their in vitro antioxidant activity (DPPH assay) and cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibition activities were evaluated. As expected, free phenolic hybrid compounds (6 and 8) showed better antioxidant activity than acetyl protected hybrid compounds (5 and 7) from DPPH assay. But the contrast result was obtained from BuChE inhibition assay. Acetyl protected hybrid compounds (5 and 7) showed better inhibition activity for BuChE than free phenolic hybrid compounds (6 and 8). Specifically, 10 (AcFA-AcFA) were shown as an effective inhibitor of BuChE ($IC_{50}=2.3{\pm}0.3{\mu}M$) and also had a great selectivity for BuChE over AChE (more than 170 fold). Inhibition kinetic studies with acetyl protected compounds (5, 7, 9, and 10) indicated that 5, 7 and 10 are a hyperbolic mixed-type inhibition and 10 is a competitive inhibition type. The binding affinity (Ki) value of 10 to BuChE is $2.32{\pm}0.15{\mu}M$.

• Bulletin of the Korean Chemical Society
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• 제34권4호
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• pp.1025-1029
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• 2013

In the previous paper (Bull. Korean Chem. Soc., 2011, 32, 2997), the hybrid molecules between ${\alpha}$-lipoic acid (ALA) and polyphenols (PPs) connected with neutral 2-(2-aminoethoxy)ethanol linker (linker-1) showed new biological activity such as butyrylcholinesterase (BuChE) inhibition. In order to increase the binding affinity of the hybrid compounds to cholinesterase (ChE), the neutral 2-(2-aminoethoxy)ethanol (linker 1) was switched to the cationic 2-(piperazin-1-yl)ethanol linker (linker 2). The $IC_{50}$ values of the linker-2 hybrid molecules for BuChE inhibition were lower than those of linker-1 hybrid molecules (except 9-2) and they also had the same great selectivity for BuChE over AChE (> 800 fold) as linker-1 hybrid molecules. ALA-acetyl caffeic acid (10-2, ALA-AcCA) was shown as an effective inhibitor of BuChE ($IC_{50}=0.44{\pm}0.24{\mu}M$). A kinetic study using 7-2 showed that it is the same mixed type inhibition as 7-1. Its inhibition constant (Ki) to BuChE is $4.3{\pm}0.09{\mu}M$.

• Bulletin of the Korean Chemical Society
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• 제32권spc8호
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• pp.2997-3002
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• 2011

A series of hybrid molecules between (R)-lipoic acid (ALA) and the acetylated or methylated polyphenol compounds were synthesized and their in vitro cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibition activities were checked. The $IC_{50}$ values of all hybrid molecules for a BuChE inhibition were lower than those of the single parent compounds. Specifically, ALA-acetyl protected caffeic acid (11, ALA-AcCA) was shown as an effective inhibitor of BuChE ($IC_{50}=0.5{\pm}0.2\;{\mu}M$) and also had a great selectivity for BuChE over AChE (more than 800 fold). Inhibition kinetic study indicated that 11 is a mixed inhibition type. Its binding affinity ($K_i$) value to BuChE is $1.52{\pm}0.18\;{\mu}M$.

• Bulletin of the Korean Chemical Society
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• 제34권11호
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• pp.3322-3326
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• 2013

A series of hybrid molecules between (${\alpha}$)-lipoic acid (ALA) and benzyl piperazines were synthesized and their in vitro cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibitory activities were evaluated. Even though the parent compounds did not show any inhibitory activity against cholinesterase (ChE), all hybrid molecules showed BuChE inhibitory activity. Some hybrid compounds also displayed AChE inhibitory activity. Specifically, ALA-1-(3-methylbenzyl)piperazine (15) was shown to be an effective inhibitor of both BuChE ($IC_{50}=2.3{\pm}0.7{\mu}M$) and AChE ($IC_{50}=30.31{\pm}0.64{\mu}M$). An inhibition kinetic study using compound 15 indicated a mixed inhibition type. Its binding affinity ($K_i$) value to BuChE is $2.91{\pm}0.15{\mu}M$.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.377.1-377.1
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• 2002

Neuroscience and molecular biology studies show that inappropriate butyrylcholinesterase (BuChE) activity as well as acetylcholinesterase (AChE) activity increases the risk and/or progression of Alzheimer's disease. BuChE may also regarded to participate in the transformation of Abeta (${\beta}$-amyloid) from an initially benign form to an eventually malignant form associated with neuritic tissue degeneration and clinical dementia. (omitted)

• Applied Biological Chemistry
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• 제38권2호
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• pp.174-178
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• 1995

유기인계 살충제인 phosalone의 활성화과정을 통한 독성발현기작에서 cytochrome $P_{450}$의 역할을 조사하기 위하여 시험관 내와 생체 내 system을 이용하였다. Phosalone의 AChE와 BuChE에 대한 이분자 저해 속도상수$(k_i)$는 약 1$10^2\;M^{-1}{\cdot}min^{-1}$으로 측정되어 그 자체로는 저해력이 상당히 낮은 약제임이 관찰되었다. AChE 또는 BuChE/MFO coupling system에서는 $I_{50}$값이 control에서 각각 $3.7{\times}10^{-6}$, $2.5{\times}10^{-7}M$로 관찰되었고, cytochrome $P_{450}$의 조효소인 NADPH를 첨가한 oxidase에서는 $1.2{\times}10^{-8}$과 $6.0{\times}10^{-9}M$로 나타나 약 $40{\sim}300$배 정도의 활성화 효과가 관찰되었다. Cytochrome $P_{450}$의 특이적 저해제인 PB를 처리하였을때 저해곡선이 control쪽으로 이동하여 phosalone의 활성화과정에 cytochrome $P_{450}$이 관여하고 있슴이 확인되었다. 그러나 생체 내 실험에서 생쥐의 뇌 AChE 활성저해는 phosalone만을 투여한 경우 $I_{50}$이 170 mg/kg, PB를 전처리 하였을 경우에서 42.5 mg/kg으로 나타나 PB 처리에 의하여 오히려 약 4배의 상승효과가 관찰되었으며, 쥐 혈액에서의 AChE와 BuChE활성저해 결과는 PB 전처리가 phosalone의 저해 경향에 큰 영향을 주지 않는 것으로 나타나 시험관 내 실험에서의 결과와는 상이하게 나타났다.

• 대한화학회지
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• 제60권2호
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• pp.125-130
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• 2016

With the goal of developing Alzheimer’s disease therapeutics, we have designed and synthesized new triazole linked decursinol derivatives having potency inhibitory activities against cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)]. Since inhibition of cholinesterase (ChE) is still considered to be one of the most effective targets to treat AD patients, many new classes of ChE inhibitors have been synthesized. In an effort of identifying new type of cholinergic drug, decursinol derivatives 11-17 have been synthesized between decursinol and other biological interesting compounds such as lipoic acid, polyphenols, etc by using the click reaction and then evaluated their biological activities. Compound 12 (IC₅₀ = 5.89 ± 0.31 mM against BuChE) showed more effective inhibitory activity against BuChE than galantamine (IC₅₀ = 9.4 ± 2.5 mM). Decursinol derivatives can be considered a new class inhibitor for BuChE and can be applied to be a novel drug candidate to treat AD patients.