• 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 $2.91{\pm}0.15{\mu}M$.

• Natural Product Sciences
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• 제25권2호
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• pp.115-121
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• 2019

Alzheimer's disease is a chronic neurodegenerative disorder with no curative treatment. The commercially available drugs, which target acetylcholinesterase, are not satisfactory. The aim of this study was to investigate the cholinesterase inhibitory activity of Solenostemma argel aerial part. Eight compounds were isolated and identified by NMR: kaempferol-3-O-glucopyranoside (1), kaempferol (2), kaempferol-3-glucopyranosyl($1{\rightarrow}6$)rhamnopyranose (3) p-hydroxybenzoic acid (4), dehydrovomifoliol (5), 14,15-dihydroxypregn-4-ene-3,20-dione (6), 14,15-dihydroxy-pregn-4-ene-3,20-dione-$15{\beta}$-D-glucopyranoside (7) and solargin I (8). Two of them (compounds 2 and 3) could inhibit over 50 % of butyrylcholinesterase activity at $100{\mu}M$. Compound (2) displayed the highest inhibitory effect against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with a slight selectivity towards the latter. Molecular docking studies supported the in vitro results and revealed that (2) had made several hydrogen and ${\pi}-{\pi}$ stacking interactions which could explain the compound potency to inhibit AChE and BChE.

• International Journal of Oral Biology
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• 제35권4호
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• pp.169-175
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• 2010

Cholinesterase (ChE) is one of the most ubiquitous enzymes and in addition to its well characterized catalytic function, the morphogenetic involvement of ChE has also been demonstrated in neuronal tissues and in non-neuronal tissues such as bone and cartilage. We have previously reported that during mouse tooth development, acetylcholinesterase (AChE) activity is dynamically localized in the dental epithelium and its derivatives whereas butyrylcholinesterase (BuChE) activity is localized in the dental follicles. To test the functional conservation of ChE in tooth morphogenesis among different species, we performed cholinesterase histochemistry following the use of specific inhibitors of developing molar and incisors in the hamster from embryonic day 11 (E11) to postnatal day 1 (P1). In the developing molar in hamster, the localization of ChE activity was found to be very similar to that of the mouse. At the bud stage, no ChE activity was found in the tooth buds, but was first detectable in the dental epithelium and dental follicles at the cap and bell stages. AChE activity was found to be principally localized in the dental epithelium whereas BuChE activity was observed in the dental follicle. In contrast to the ChE activity in the molars, BuChE activity was specifically observed in the secretory ameloblasts of the incisors, whilst no AChE activity was found in the dental epithelium of incisors. The subtype and localization of ChE activity in the dental epithelium of the incisor thus differed from those of the molar in hamster. In addition, these patterns also differed from the ChE activity in the mouse incisor. These results strongly suggest that ChE may play roles in the differentiation of the dental epithelium and dental follicle in hamster, and that morphogenetic subtypes of ChE may be variable among species and tooth types.

• 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.

• Ocean and Polar Research
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• 제39권1호
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• pp.45-49
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• 2017

During the search for anticholinesterase compounds from marine organisms, we were able to isolate 6,6'-bieckol from a red alga, Grateloupia elliptica. This compound showed moderate acetylcholinesterase (AChE) inhibitory activity in a micromole range ($IC_{50}$ $44.5{\mu}M$). However, for butyrylcholinesterase (BuChE), a new target for the treatment of Alzheimer's disease (AD), it showed particularly potent inhibitory activity ($IC_{50}$ $27.4{\mu}M$), which is more potent compared to AChE. It also inhibits BACE-1, a new target for reducing the generation of ${\beta}-amyloid$.

• Environmental Analysis Health and Toxicology
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• 제8권1_2호
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• pp.1-10
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• 1993

This study was done to determine the toxic effect of fthalide in rats which have oral administration at levels of 100 mg/kg/day for twelve days. It was examined the hematogram and serological parameters, and also the content of cytochrome P-450, the activity of NADPH-cytochrome c reductase, glucose-6-phosphatase, cholinesterase and carboxylesterase in liver. Any significant alteration of hematogram was not found but the value of AST, LDH and content of glucose in serum were statistically increased. The content of cytochrome P-450, the activty of NADPH-cytochrome c reductase were increased but glucose-6-phosphatase were slightly decreased compare with that of control group. The activity of cholinesterase was decreased slightly and on the contrary the activity of carboxylesterase was found to be the tendeny of increase in both of liver and serum.

• 한국환경보건학회지
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• 제22권3호
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• pp.8-16
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• 1996

Effects of water extract of aloe vera on lead-induced neurotoxicity were investigated in sciatic nerve isolated from rat. The mechanism on toxicity reduction by measuring activities of axonal enzymes, metabolism of myo-inositol in nerve, lead concentration in several organs and so on were further examimed. In the lead-treated rats, the transport rate of axonal enzyme, such as acetyl cholinesterase and choline acetyltransferase, was reduced by from 50% to 30% respectively. Reduction in myo-inositol concentration and $Na^+/K^+$ ATPase activity were also observed in sciatic nerve from lead-treated rat. However, the aloe extract administration significantly eliminated the impairment and maintained myo-inositol concentration to about 85% of normal level. Also aloe extract promoted the excretion rate of lead which is accumulated in blood, sciatic nerve and kidney. These results suggest that lead-induced neurotoxicity was significantly reduced by administration of aloe extract and the mechanism might be partly increase in kidney excretion rate of lead and parity normalization of $Na^+/K^+$ ATPase activity which is critical factor in order to keep nerve maintaining normal myo-inositol level.

• 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.

• Advances in Traditional Medicine
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• 제7권2호
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• pp.182-190
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• 2007

Alzheimer's disease is a neurodegenerative disorder associated with a decline in cognitive abilities. Dementia is one of the aged related mental problems and a characteristic symptom of Alzheimer's disease. Nootropic agents like piracetam and cholinesterase inhibitors like $Donepezil^{\circledR}$ are used in situations where there is organic disorder in learning abilities, but the resulting side-effects associated with these agents have limited their utility. Foeniculum (F.) vulgare Linn. is widely used in Indian traditional systems of medicines and also as a house remedy for nervous debility. The present work was undertaken to assess the potential of F. vulgare as a nootropic and anti-cholinesterase agent in mice. Exteroceptive behavioral models such as Elevated plus maze and Passive avoidance paradigm were employed to assess short term and long term memory in mice. To delineate the possible mechanism through which F. vulgare elicits the anti-amnesic effects, its influence on central cholinergic activity was studied by estimating the whole brain acetylcholinesterase activity. Pretreatment of methanolic extract of fruits of F. vulgare Linn. for 8 successive days, ameliorated the amnesic effect of scopolamine (0.4 mg/kg) and aging induced memory deficits in mice. F. vulgare extract significantly decreased transfer latencies of young mice and aged mice, increased step down latency and exhibited significant anti-acetyl cholinesterase effects, when compared to piracetam, scopolamine and control groups of mice. F. vulgare might prove to be a useful memory restorative agent in the treatment of dementia seen in the elderly.

• Current Research on Agriculture and Life Sciences
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• 제6권
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• pp.171-180
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• 1988

parathion을 rat의 복강내에 매 3일 마다 20회 반복적으로 주사 했을때, 일정한 농도의 parathion을 주사한 rat와 점진적으로 주사량을 증가 시켰을때 rat의 독성정도, 혈액 및 신경조직내 cholinesterase 활성 변화, 혈액내 urea nitrogen 및 creatinine의 함량을 측정한 결과 다음과 같은 성적을 얻었다. 복강내 주사시 rat에 대한 parathion의 $LD_{50}$는 10.5mg/kg였으며 95% 신뢰한계는 6.6~16.8mg/kg였다. 아급성 독성실험에서는 A군이 50%의 폐사율을 보인데 비하여 B군과 C군에서 각각 57% 및 83%의 폐사율을 보여 parathion에 대한 축적효과가 나타났으며 증체량 측정에서도 A군에서 123 g의 증체량을 보인데 비하여 B군과 C군에서 각각 60.7 g, 및 88.4 g 의 증체량을 보여 parathion 투여군에서 체중 증가량이 감소하였다. 혈장내 cholinesterase 활성도는 A군($0.58U/m{\ell}$)에 비해 B군($0.47U/m{\ell}$)과 C군($0.36U/m{\ell}$)에서 각각 19%, 및 38%의 억제를 보였고 AA군($0.31U/m{\ell}$), BB군($0.26U/m{\ell}$) 및 CC군($0.17U/m{\ell}$)에서도 A군에 비해 각각 47%, 55%, 71%까지 유의성(P<.05)있는 감소를 보였다. 척수내 cholinesterase 활성도는 A군(2.484U/g)에 비해 B군(1.87U/g)과 C군(1.29U/g)에서 각각 25%, 및 48%의 억제를 보였고 AA군(1.27U/g), BB군(0.71U/g) 및 CC군(0.25U/g)에서도 A군에 비하여 각각 49%, 71%, 및 90%의 유의성(P<.01)있는 억제를 보였다. 뇌의 cholinesterase 활성도에서는 A군(4.67U/g)에 비해 B군(2.52U/g)과 C군(1.32U1U/g)에서 각각 46%, 및 72%로 억제 되었고 AA군(2.48U/g), BB군(1.08U/g) 및 CC군(0.51U/g)에서는 A군에 비해 각각 47%, 77%, 89%까지 유의성(P<.01)있게 억제되는 축적효과를 보였다. 비단백 질소 화합물이 urea nitrogen과 creatinine 함량은 A군에서 각각 $39.8mg/d{\ell}$와 $1.15mg/d{\ell}$인데 비하여 B군($40.9mg/d{\ell}$, $0.90mg/d{\ell}$) 및 C군($41.4mg/d{\ell}$, $1.08mg/d{\ell}$)에서 유의성 있는 차이를 보이지 않았으나 urea nitrogen 함량은 A군에 비해 B군과 C군에서 다소 증가하는 경향을 보였다.