• 한국응용곤충학회지
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• 제10권1호
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• pp.13-22
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• 1971

이 실험은 이화명나방 월동 유충에 대한 유기인 살출제의 in vitro에 있어서의 ChE저해력과 약제의 화학 구조와의 관계, in vivo에 있어서의 국소 시용법에 의한, 살충제의 독성과 화학 子조와의 관계, 특히 ChE 저해력과 살충력(독성)과의 관계를 비교 연구할 목적으로 실험하였으며 그 결과를 다음과 같이 요약할 수 있다. 1, Phosphate compounds는 thiophosphate compounds보다 in vitro에 있어서의 ChE 저해력은 강하다고 할 수 있으나 in vivo에 있어서의 독성은 비례적으로 반드시 강하다고 할 수 없다. 2. Alcoxy 즉 diethoxy는 dimethoxy보다 ChE 저해력과 독성이 비례적으로 반드시 강하다고 할 수 없다. 3. $(RO)_2PO(S)X$ 부분에 있어서 이 X부분이 달라짐에 따르는 ChE 저해력과 살충력에 대해서는 약제에 따라서 각각 다르게 나타나므로 언급할 수 없다. 4. ChE 저력이 강한 약제는 살충력도 비례적으로 강하다고 할 수 없다. 그러나 화학 구조상 안정성이고 실용 농약인 Ethylparathion, Malathion, Let aycid, EPN, Sumithion 및 Diazinon 등에서 고찰할 때 반드시 비례적인 것은 아니나 어느 정도의 파행 관계가 있지 않은가 추찰된다.

• 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.

• 한국환경과학회지
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• 제11권4호
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• pp.391-397
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• 2002

Carbamate 농약에 대한 cholinesterase(ChE)활성저해 관계를 규명 하고자 in vivo와 in vitro 실험을 하였다. ChE의 최적 pH는 8.0이었다. 병아리 혈장의 ChE 활성은 기질로 acetylcholin를 사용할 경우 24.6 $\mu$mol/min/g protein이었다. in vivo에서 BPMC을 0.32 mg/kg 경구 투여한 15분 후에 ChE 활성이 60%까지 저해되었으며 그 후 12시간 후에 97% 까지 회복이 일어났다. in vitro에서 효소 활성이 50%로 저해되는데 필요한 농도인 I$_{50}$이 Phenyl N-methylcarbamate계에 XMC는 329 $\mu\textrm{g}$/$\ell$였고, metolcarb은 214 $\mu\textrm{g}$/$\ell$였다. BPMC는 111 $\mu\textrm{g}$/$\ell$, propoxur는 107 $\mu\textrm{g}$/$\ell$, isoprocarb는 104 $\mu\textrm{g}$/$\ell$이었다. Aromatic N-methylcarbamate계에 속하는 carbaryl의 I$_{50}$은 280 $\mu\textrm{g}$/$\ell$이었고, carbofuran 114 $\mu\textrm{g}$/$\ell$이었다.이었다.

• 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.

• Environmental Analysis Health and Toxicology
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• 제2권1_2호
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• pp.17-24
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• 1987

Changes in cholinesterase (ChE) activity, electrophoretic pattern of ChE and histopathologic state on the mice serum, brain and liver by administration of organophos-phorous insecticides were studied. The mice ChE activities on serum, brain and liver decreased by increasing of concentration and time both administration of malathion and DDVP, whereas on serum and brain the activities of the 7 days after administration decreased, and then presented the gradually slight recovery in course of time. The ChE on serum and liver showed many isozyme bands by polyacrylamide gel electrophoresis but several on brain. And isozyme bands disappeared and diffused by administration of organophosphorous insecticides and development of time. The mice liver with administration group of malathion on histopathologic test showed midzonal necrosis between central vein and portal area, and with administration group of DDVP mainly presented portal necrosis on location of potal area.

• 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 $2.91{\pm}0.15{\mu}M$.

• 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.

• 농약과학회지
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• 제5권1호
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• pp.12-18
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• 2001

유기인계 농약에 대한 cholinesterase(ChE)활성저해 관계를 규명 하고자 in vivo와 in vitro 실험을 하였다. 병아리 혈장의 ChE 활성은 $23{\mu}mol$/min/g protein이었다. in vivo에서 terbufos의 투여량을 $LD_{50}$의 0.2배(0.362 mg/kg)와 0.5배(0.905 mg/kg)로 투여하였을 경우, 투여 15분 후에 ChE 활성이 각각 36%와 96%까지 저해되었으며 그 후 회복이 일어난다. in vitro에서 유기인계의 P에 S가 결합된 P=S구조의 phosphorodithioate와 phosphorothioate의 Ki는 $74{\sim}322\;mole^{-1}min^{-1}$로 낮았다. 그러나 P에 S가 산화되어 O가 결합된 P=O구조의 phosphate와 phosphorothiolate의 Ki는 $13898{\sim}79610\;mole^{-1}min^{-1}$로 높았다. 따라서 P=S가 P=O로 산화됨으로서 ChE의 저해도가 커져서 독성이 강해짐을 확인하였다. phosphorodithioate와 phosphorothioate형의 $pI_{50}$값은 $21{\sim}102 mg/L(ppm)$ 이었다. 그러나 phosphate와 phosphorothiolate형의 $pI_{50}$값은 $0.519{\sim}0.071$ mg/L(ppm)이었다. 즉 ChE을 이용한 enzyme-inhibition(EI)법을 유기인계 농약의 정성적 검출에 이용한다면, P=O구조인 phosphate와 phosphorothiolate형은 1ppm이하 즉 ppb단위까지 정성적 검출이 가능하다.

• Journal of Preventive Medicine and Public Health
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• 제25권2호
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• pp.180-188
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• 1992

The effects of multiple exposures to pesticides on plasma cholinesterase(ChE) activities and urinary p-nitrophenol excretion were evaluated in rats. Rats were received single dose i.p. with $LD_{50}/100(mg/kg)$ of organophosphorous(OP), organophosphorous-organochroline(OP-OC), organophosphorous-carbamate(OP-CAB), organophosphorous-organoarsenate(OP-OA) pesticides for 4 consecutive days. In repeated administration of pesticides, plasma ChE activities were decreased, but urinary p-nitrophenol were increased after the first injection and then decreased gradually The recovery rates of ChE activities and p-nitrophenol excretion at 48 hours after the fourth Injection were delayed in comparision with the baseline value of 24 hours before the first injection. Statistical significances were found between OP and other groups except OP-OA group after the second injection in plasma ChE activities, but in urinary p-nitrophenol excretion there was statistical significance only between OP and OP-CAB.

• Environmental Analysis Health and Toxicology
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• 제17권3호
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• pp.265-272
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• 2002

Enzyme-Inhibition방법으로 다성분 잔류 농약의 검출 기법을 개발하기 위해, 음용수 허용기준 설정 농약인 유기인계 농약으로 malathion, parathion, diazinon과 carbamate농약으로 carbary에 대한 acetylcholinesterase (AChE)과 cholinesterase (ChE) 활성저해 관계를 규명하였다. 병아리 뇌의 AChE와 ChE 활성도는 각각 166.6 및 5.8$\mu$mol/min/g protein이었고, 혈장에서는 각각 23.1$\mu$mol/min/g protein과 8.3 $\mu$mol/min/g protein 이었다. AChE와 ChE의 최적 PH는 각각 8.2및 7.8 이었다. Km은 0.034 및 0.045 mM 이었다. 유기인계농약에서 AChE와 ChE의 I$_{50}$ 값의 malathion이 55.82 및 99.42mg/L이었고, Parathion은 31.16및 29.13mg/L이었고, diazinon은 17.89 및 19.62 mg/L 이었다. Carbamate농약인 carbaryl의 AChE와 ChE의 I$_{50}$ 값의 0.10및 0.05mg/L이었다. 먹는 물 관리법에 의한 carbaryl의 먹는 물 허용 수질기준인 0.07mg /L을 AChE와 ChE의 I$_{50}$에서 검출할 수 있다. AChE및 ChE을 이용한 enzyme-inhibition(EI)법은 carbamate농약인 carbaryl을 먹는 물 허용 수질기준인 0.07mg/L가지 검출 할 수 있으므로, 다성분 잔류분석법 (MRM, Multiresidue Method)으로 이용할 수 있다. 따라서 Enzyme lnhibition방법을 이용하여 자연환경 중 carbamate계 농약을 쉽고 빠르게 검출할 수 있는 새로운 bioassay법으로 응용할 수 있다. 수 있다.