• Journal of Microbiology and Biotechnology
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• 제25권9호
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• pp.1425-1428
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• 2015

Monoamine oxidase (MAO) is found in most cell types and catalyzes the oxidation of monoamines. Three anithiactins (A-C, modified 2-phenylthiazoles) isolated from Streptomyces sp. were tested for inhibitory activity of two isoforms, MAO-A and MAO-B. Anithiactin A was effective and selective for the inhibition of MAO-A, with an IC₅₀ value of 13.0 μM; however, it was not effective for the inhibition of MAO-B. Anithiactins B and C were weaker inhibitors for MAO-A and MAO-B. Anithiactin A was a reversible and competitive inhibitor for MAO-A with a K_i value of 1.84 μM. The hydrophobic methyl substituent in anithiactin A may play an important role in the inhibition of MAO-A. It is suggested that anithiactin A is a selective reversible inhibitor for MAO-A, with moderate potency, and can be considered a new potential lead compound for further development of novel reversible inhibitors for MAO-A.

• Biomolecules & Therapeutics
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• 제5권3호
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• pp.228-232
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• 1997

AU-164 was synthesized as a reversible gastric $H^+/K^+$ ATPase inhibitor, and its effects were tested in various systems. AU-164 inhibited rabbit gastric $H^+/K^+$ ATPase with an $IC_{50}$/ of 9 $\mu$M. On the other hand, AU-164 was a weak inhibitor for dog kidney $Na^+/K^+$ ATPasc, indicating the selectivity for gastric $H^+/K^+$ ATPase. The reversible property of the AU-164-induced inhibition of $H^+/K^+$ ATPase was confirmed by filtering the inhibition mixture through Sephadex G-25M column. In vivo basal acid secretion was also inhibited by AU-164 under the pylorus ligation of Sprague-Dawley rats. In addition, AU-164 protected dose dependently gastric lesion induced by ethanol in rats. The $ED_{50}$ value of 62 mg/kg p.o was estimated. These results suggest that AU-164 is a potent, selective and reversible gastric $H^+/K^+$ ATPase inhibitor, and that AU-164 has a potential use for the clinical therapeutics of peptic ulcer disease.

• 한국식품영양과학회지
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• 제22권3호
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• pp.280-285
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• 1993

동물체내에서 천식, 염증, 혈소판 응고 등에 관련된 매개체를 생성시키는 효소인 lipoxygenase작용기 전과 유사한 대두 lipoxygenase (Type IV)를 사용하여 생마늘의 수용액, 에탄올, 클로로포름 추출분획에 의한 lipoxygenase 저해 정도를 측정하였다. 효소를 클로로포름 추출 분획과 10분 preincuba-tion시킨 후의 효소 저해 양상은 비가역적 저해(1$_{50}$값, 55mg/$m\ell$)이었으며, 수용액 추출 분획의 경우는 주로 가역적 저해 양상(1$_{50}$값, 65mg/$m\ell$)을 나타내었다. 한편, diallyldisulfide와 dimethyldisulfide의 1$_{50}$값은 각각 1.3mM, 18mM 이었으며 이들은 가역적, 비가역적 저해 현상을 모두 나타내었다. 합성품 alliin은 비교적 높은 농도(10mM농도에서 22%저해)에서 저해하였으며, alliin의 분해산물은 비가역적 저해 양상을 나타낸 반면에, S-ethylcysteine sulfoxide는 효소를 거의 저해하지 않았다. 따라서 다진 마늘 속에는 가역적 저해제가 주로 함유되어 있고, 소량(25~30%)의 비가역적 저해제가 함유되어 있는 것으로 사료되었다.사료되었다.

• Journal of Microbiology and Biotechnology
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• 제27권2호
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• pp.316-320
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• 2017

Alternariol monomethyl ether (AME), a dibenzopyrone derivative, was isolated from Alternaria brassicae along with altertoxin II (ATX-II). The compounds were tested for the inhibitory activity of monoamine oxidase (MAO), which catalyzes neurotransmitting monoamines. AME was found to be a highly potent and selective inhibitor of human MAO-A with an $IC_{50}$ value of $1.71{\mu}M$; however, it was found to be ineffective for MAO-B inhibition. ATX-II was not effective for the inhibition of either MAO-A or MAO-B. The inhibition of MAO-A using AME was apparently instantaneous. MAO-A activity was almost completely recovered after the dilution of the inhibited enzyme with an excess amount of AME, suggesting AME is a reversible inhibitor. AME showed mixed inhibition for MAO-A in Lineweaver-Burk plots with a $K_i$ value of $0.34{\mu}M$. The findings of this study suggest that microbial metabolites and dibenzopyrone could be potent MAO inhibitors. In addition, AME could be a useful lead compound for developing reversible MAO-A inhibitors to treat depression, Parkinson's disease, and Alzheimer's disease.

• Bulletin of the Korean Chemical Society
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• 제3권3호
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• pp.122-129
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• 1982

In order to extend our understanding on the multiple inhibition enzyme kinetics, a general equation of an enzyme reaction in the presence of two different reversible inhibitors was derived by what we call "match-box mechanism" under the combined assumption of steady-state and quasi-equilibrium for inhibitor binding. Graphical methods were proposed to analyze the multiple inhibition of an enzyme by any given sets of different inhibitors, i.e., competitive, noncompetitive, and uncompetitive inhibitors. This method not only gives an interaction factor $({\alpha})$ between two inhibitors, but also discerns ${\alpha}_1$ and ${\alpha}_2$ with and without substrate binding, respectively. The factors involved in the dissociation constants of inhibitors can also be evaluated by the present plot. It is also shown that the present kinetic approach can be extended to other forms of activators or hydrogen ions with some modification.

• 한국연초학회지
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• 제9권2호
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• pp.69-75
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• 1987

Nicotine, the main alkaloid of tobacco, showed different effect according to the enzyme. Among investigated enzymes, protease was inactivated remarkably by nicotine and the mode of inhibition was examined. $\alpha$-amylase and $\beta$-amylase were not affected, and cellulase and glucoamylase were inactivated partially when the concentration of it was over 1.0% , but protease was inhibited powerfully by nicotine The inhibition of protease by nicotine was performed almost in the initial stage of reaction, and was not so much affected by temperature, and was reversible. The inhibition type of protease by nicotine appeared as a Mixed-type inhibition.

• Journal of Applied Biological Chemistry
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• 제61권2호
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• pp.187-190
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• 2018

Two curcumin derivatives, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), isolated from Curcuma longa were analyzed for their inhibitory activities against two isoforms of monoamine oxidase (MAO), which is involved in the catalysis of neurotransmitting monoamines. In the study, DMC and BDMC potently inhibited human MAO-B, with $IC_{50}$ values of 2.45 and $2.59{\mu}M$, respectively, and both compounds showed effective inhibitory activities against human MAO-A, with $IC_{50}$ values of 3.24 and $3.09{\mu}M$, respectively. The inhibitory activities of the two compounds were higher than those of curcumin. The removal of the methoxy or dimethoxy groups in curcumin might increase the inhibitory activities against human MAO-A and MAO-B. The inhibited activities were recovered to almost the values of the reversible references in the dialysis experiments with DMC and BDMC. DMC and BDMC showed competitive inhibition for MAO-A and MAO-B, respectively, with $K_i$ values of 0.91 and $0.80{\mu}M$, respectively. These results suggest that the two curcumin derivatives may be useful or lead compounds in the treatment of related disorders as potent reversible MAO inhibitors.

• 대한화학회지
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• 제20권5호
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• pp.406-416
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• 1976

Pyridine관여 탈수소 효소는 $N^1$-alkylnicotinamide chloride 유도체에 의하여 저해 작용을 받고 있는 바 저해제이 농도 변화에 따른 효소 저해작용이 가역 또는 비가역 불활성화 반응에 기인하는지의 여부를 밝혀 보기 위하여 토끼 근육으로 부터 유리한 L-${\alpha}$-glycerophosphate dehydrogenase를 사용하여 연구하였다. 이 효소의 저해작용은 상용한 저해제 유도체의 농도가 희박했을 경우 가역적인 효소저해 반응을 보여주고 있으나 저해제의 농도가 증가함에 따라 점차 비가역적인 효소 불활성화로서 나타남을 알았으며 이러한 비가역 불활성화 반응은 저해제의 농도가 증가함에 따라 형성될 수 있는 micelle 구조의 미세분자와의 결합에 의한 효소의 변성에 기인할 것이라고 결론을 얻었다.

• Journal of Microbiology
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• 제42권3호
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• pp.223-227
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• 2004

An ${\alpha}$-glucosidase inhibitor, SKG-3, was isolated from the fruiting bodies of Ganoderma lucidum and its physico-chemical properties were characterized. It was a highly specific and effective reversible inhibitor of ${\alpha}$-glucosidase. It showed very potent inhibitory activity against a-glucosidase with an IC$\sub$50/ value of 4.6$\mu\textrm{g}$/$m\ell$, but no activity for any other glycosidases tested. Enzyme activity could be recovered upon dialysis, thus providing evidence for the reversibility of the inhibition. A Lineweaver-Burk plot indicated that the SKG-3 inhibition of ${\alpha}$-glucosidase was competitive.

• BMB Reports
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• 제36권2호
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• pp.149-153
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• 2003

The dibucaine number (DN) was determined for serum cholinesterase (EC 3.1.1.8, SChE) in plasma samples. The ones with a DN of 79-82 were used, because they had the "usual" SChE variant. The enzyme was assayed colorimetrically by the reaction of 5,5'-dithiobis-[2-nitrobenzoic acid] (DTNB) with the free sulfhydryl groups of thiocholine that were produced by the enzyme reaction with butrylthiocholine (BuTch) or acetylthiocholine (AcTch) substrates, and measured at 412 nm. Dibucaine, a quaternary ammonium compound, inhibited SChE to a minimum within 2 min in a reversible manner. The inhibition was very potent. It had an $IC_{50}$ of $5.3\;{\mu}M$ with BuTch or $3.8\;{\mu}M$ with AcTch. The inhibition was competitive with respect to BuTch with a $K_i$ of $1.3\;{\mu}M$ and a linear-mixed type (competitive/noncompetitive) with respect to AcTch with inhibition constants, $K_i$ and $K_I$ of 0.66 and $2.5\;{\mu}M$, respectively. Dibucaine possesses a butoxy side chain that is similar to the butryl group of BuTch and longer by an ethylene group from AcTch. This may account for the difference in inhibition behavior. It may also suggest the existence of an additional binding site, other than the anionic binding site, and of a hydrophobic nature.