• Bulletin of the Korean Chemical Society
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• v.3 no.3
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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.

• Journal of Microbiology and Biotechnology
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• v.25 no.9
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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.

• Molecular & Cellular Toxicology
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• v.2 no.3
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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.

• Journal of the Korean Chemical Society
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• v.20 no.5
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• pp.406-416
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• 1976

A series of $N^1$-alkylnicotinamide chlorides, $N^1$-methyl-to $N^1$-dodecylnicotinamides inclusive were studied with rabbit muscle L-${\alpha}$-glycerophosphate dehydrogenase to investigate the possibility of reversible and irreversible inactivation of the pyridine-linked dehydrogenases by the coenzyme-competitive inhibitor derivatives. The inhibition of the enzyme by $N^1$-alkylnicotinamide chlorides was demonstrated to be reversible at the dilute concentration of the inhibitors but this reversible inhibition was found to be followed by an irreversible time-dependent inactivation measuable at high concentrations of the inhibitors. The properties of this time-dependent inactivation were discussed on the basis of the denaturation of the enzyme by the binding of small micelle-like structures formed at higher concentrations of the inhibitors.

• Bulletin of the Korean Chemical Society
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• v.17 no.1
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• pp.34-38
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• 1996

2-(Azetidin-2-one-1-yl)-3-phenylpropionic acid and 2-(azetidin-2-thione-1-yl)-3-phenylpropionic acid were designed as potential active site directed inactivators for carboxypeptidase A, but shown to be they are competitive reversible inhibitors for the enzyme. The observation was somewhat surprising, but is not unexpected considering the recent report of Page who questioned the validity of the generally believed notion that $\beta-lactam$ ring is highly unstable.

• Journal of Microbiology and Biotechnology
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• v.31 no.7
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• pp.1022-1027
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• 2021

Three compounds were isolated from marine-derived Streptomyces sp. CNQ-031, and their inhibitory activities against monoamine oxidases (MAOs), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase (BACE-1) were evaluated. Compound 1 (5,7-dihydroxy-2-isopropyl-4H-chromen-4-one) was a potent and selective inhibitor of MAO-A, with a 50% inhibitory concentration (IC₅₀) of 2.70 µM and a selectivity index (SI) of 10.0 versus MAO-B. Compound 2 [5,7-dihydroxy-2-(1-methylpropyl)-4H-chromen-4-one] was a potent and low-selective inhibitor of MAO-B, with an IC₅₀ of 3.42 µM and an SI value of 2.02 versus MAO-A. Compound 3 (1-methoxyphenazine) did not inhibit MAO-A or MAO-B. All three compounds showed little inhibitory activity against AChE, BChE, and BACE-1. The K_i value of compound 1 for MAO-A was 0.94 ± 0.28 µM, and the K_i values of compound 2 for MAO-A and MAO-B were 3.57 ± 0.60 and 1.89 ± 0.014 µM, respectively, with competitive inhibition. The 1-methylpropyl group in compound 2 increased the MAO-B inhibitory activity compared with the isopropyl group in compound 1. Inhibition of MAO-A and MAO-B by compounds 1 and 2 was recovered by dialysis experiments. These results suggest that compounds 1 and 2 are reversible, competitive inhibitors of MAOs and can be considered potential therapies for neurological disorders such as depression and Alzheimer's disease.

• Journal of Applied Biological Chemistry
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• v.61 no.2
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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.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.233.1-233.1
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• 2002

Azasugars, which have been called the "sugar-shaped" alkaloids from plants. are reversible. competitive inhibitors of glycosidases. The purpose of these natural products is possibly to inhibit the carbohydrate metabolism and consequently the growth of plant consuming pests. Since selective glycosidase inhibitors have a large number of interesting potential applications including treatment of AIDS, diabetes. and tumor metastasis. they have received a considerable attentions. (omitted)

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.100-100
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• 1997

To treat peptic ulcer diseases, many potent proton pump inhibitors have been developed for suppressing the gastric acid secretion in clinical patients. However, most of these agents have common irreversible mechanisms against H$\^$+/, K$\^$+/-ATPase which might be the cause of hypergastrinemia and ECL cell hyperplasia. Therefore, the development of new reversible inhibitors is prompted. In this study, we investigated the inhibitory mechanism of a newly synthesized proton pump inhibitor, YJA20379-8 using lyophilized hog gastric microsomes. YJA20379-8 inhibited K$\^$+/-stimulated H$\^$+/K$\^$+/-ATPase activity uncompetitively with respect to K$\^$+/, and in the other hand, showed competitive inhibitory pattern with ATP, respectively. From these data, we suggest that YJA20379-8 may be a proton pump inhibitor with a new inhibitory mechanism.

• Journal of Microbiology and Biotechnology
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• v.27 no.4
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• pp.785-790
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• 2017

Two piloquinone derivatives isolated from Streptomyces sp. CNQ-027 were tested for the inhibitory activities of two isoforms of monoamine oxidase (MAO), which catalyzes monoamine neurotransmitters. The piloquinone 4,7-dihydroxy-3-methyl-2-(4-methyl-1-oxopentyl)-6H-dibenzo[b,d]pyran-6-one (1) was found to be a highly potent inhibitor of human MAO-B, with an $IC_{50}$ value of $1.21{\mu}M$; in addition, it was found to be highly effective against MAO-A, with an $IC_{50}$ value of $6.47{\mu}M$. Compound 1 was selective, but not extremely so, for MAO-B compared with MAO-A, with a selectivity index value of 5.35. Compound 1,8-dihydroxy-2-methyl-3-(4-methyl-1-oxopentyl)-9,10-phenanthrenedione (2) was moderately effective for the inhibition of MAO-B ($IC_{50}=14.50{\mu}M$) but not for MAO-A ($IC_{50}$ > $80{\mu}M$). There was no time-dependency in inhibition of MAO-A or -B by compound 1, and the MAO-A and -B activities were almost completely recovered in the dilution experiments with an excess amount of compound 1. Compound 1 showed competitive inhibition for MAO-A and -B, with $K_i$ values of 0.573 and $0.248{\mu}M$, respectively. These results suggest that piloquinones from a microbial source could be potent reversible MAO inhibitors and may be useful lead compounds for developing MAO enzyme inhibitors to treat related disorders, such as depression, Parkinson's disease, and Alzheimer's disease.