• BMB Reports
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• 제44권12호
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• pp.811-815
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• 2011

Inhalational anthrax is caused by B. anthracis, a virulent sporeforming bacterium which secretes anthrax toxins consisting of protective antigen (PA), lethal factor (LF) and edema factor (EF). LF is a Zn-dependent metalloprotease and is the main determinant in the pathogenesis of anthrax. Here we report the identification of a lead small-molecule inhibitor of anthrax lethal factor by screening an available synthetic small-molecule inhibitor library using fluorescence-based high-throughput screening (HTS) approach. Seven small molecules were found to have inhibitory effect against LF activity, among which SM157 had the highest inhibitory activity. All theses small molecule inhibitors inhibited LF in a noncompetitive inhibition mode. SM157 and SM167 are from the same family, both having an identical group complex, which is predicted to insert into S1' pocket of LF. More potent small-molecule inhibitors could be developed by modifying SM157 based on this identical group complex.

• Bulletin of the Korean Chemical Society
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• 제28권3호
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• pp.379-385
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• 2007

Receptor-oriented pharmacophore-based in silico screening is a powerful tool for rapidly screening large number of compounds for interactions with a given protein. Inhibition of the enzyme catechol-Omethyltransferase (COMT) offers a novel possibility for treating Parkinson's disease. Bisubstrate inhibitors of COMT containing the adenine of S-adenosylmethionine (SAM) and a catechol moiety are a new class of potent and selective inhibitor. In the present study, we used receptor-oriented pharmacophore-based in silico screening to examine the interactions between the active site of human COMT and bisubstrate inhibitors. We generated 20 pharmacophore maps, of which 4 maps reproduced the docking model of hCOMT and a bisubstrate inhibitor. Only one of these four, pharmacophore map I, effectively described the common features of a series of bisubstrate inhibitors. Pharmacophore map I consisted of one hydrogen bond acceptor (to Mg2+), three hydrogen bond donors (to Glu199, Glu90, and Gln120), and one hydrophobic feature (an active site region surrounded by several aromatic and hydrophobic residues). This map represented the most essential pharmacophore for explaining interactions between hCOMT and a bisubstrate inhibitor. These results revealed a pharmacophore that should help in the development of new drugs for treating Parkinson's disease.

• The Plant Pathology Journal
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• 제16권3호
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• pp.125-129
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• 2000

A rapid and efficient assay to determine melanin biosynthesis inhibition of Magnaporthe grisea, a causal agent of the rice blast, by chemicals was developed. Wells in 24-well plates were loaded with spore suspension of the fungus and three known melanin biosynthesis inhibitors of KC10017, tricyclazole, and carpropamid. Subsequent color changes of mycelia and culture media in the wells were observed 7 days after incubation. The wells treated with KC10017 (an inhibitor of polyketide synthesis step and/or pentaketide cyclization step) became colorless, whereas tricyclazole (an inhibitor of 1, 3, 8-trihydroxynaphthalene reductase) or carpropamid (an inhibitor of scytalone dehydratase)-treated wells exhibited red color. They did not show any inhibitory effect on fungal growth. The inhibition of reaction steps prior to 1, 3, 6, 8-tetrahydroxynaphthalene formation was easily determined by colorless medium and mycelia. However, it was impossible to distinguish between inhibition of reduction steps and inhibition of dehydration steps by colors of the cultures. It was accomplished through HPLC analysis of the melanin biosynthesis-involving pentaketide metabolites accumulated by the inhibitors. Through screening of a number of synthetic chemicals using the in vitro assay, we could find a novel chemical group of melanin biosynthesis inhibitor.

• Environmental Analysis Health and Toxicology
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• 제16권3호
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• pp.115-120
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• 2001

The predictive screening of various molecular descriptors for predicting cyclooxygenase inhibitor, lipooxygenase inhibitor, leucotriene synthesis inhibitor, leucotriene antagonist activities of Stilbene moieties have been investigated for the application of quantitative structure-activity relationships (QSAR). The biological activities for 36 compounds were computed by the PASS program and molecular descriptors are cited from literatures or calculated, to investigate feasibility of screening relevant descriptors and of their applications among biological endpoints. Fairly good correlations varying from 0.7828 to 0.9032 were obtained using 12 descriptors with 29 Stilbene derivatives and 5 diazo-compounds. Our studies reveal that LogKow, electron density(X), electron density (Y),4th-order valence connectivity and water solubility can be usefully employed to predict biological activities of stilbene derivatives with simple regression models.

• 한국미생물·생명공학회지
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• 제17권2호
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• pp.115-120
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• 1989

세포외로 pepsin 저해물질을 생산하는 미생물을 획득할 목적으로 screening test를 실시하여, porcine pepsin에 대하여 우수한 저해력을 나타내는 방선균 1균주(GF 155-2)를 분리하였다. 각종 배지상에서 그 형태학적·배양학적·생리학적 성질을 조사하여 본 결과 그 미생물학적 특성이 Microtetraspora속과 유사하였다.

• 한국미생물·생명공학회지
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• 제23권3호
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• pp.311-315
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• 1995

Assay conditions for screening of $\beta$-1,3-glucan synthase inhibitor were evaluated. Cells in the beginning of mid-log phase showed the highest activity of the $\beta$-1,3-glucan synthase. Cells permeabilized with 1% digitonin treatment could be used as a good crude enzyme source for convenient screening of the $\beta$-1,3-glucan synthase inhibitors. Calcofluor white (0.125% in final) and papulacandin B (25 $\mu$g/ml) inhibit 90% and more than 50% of the $\beta$-1,3-glucan synthase activity, respectively. Cells grown at 37$\circ$C showed higher enzyme activity than those of 25$\circ$C. Catalytic factor of the $\beta$-1,3-glucan synthase was solubilized from particulated membrane preparations, holoenzyme, by extracting with 0.00938% CHAPS.

• 대한약학회:학술대회논문집
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• 대한약학회 2000년도 NEW STRATEGY FOR DRUG DEVELOPMENT IN POST-GENOMIC ERA(대한약학회)
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• pp.266.3-267
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• 2000

• 대한약학회:학술대회논문집
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• 대한약학회 2000년도 NEW STRATEGY FOR DRUG DEVELOPMENT IN POST-GENOMIC ERA(대한약학회)
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• pp.266.2-266.2
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• 2000

• Bulletin of the Korean Chemical Society
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• 제31권12호
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• pp.3644-3652
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• 2010

The metallo-$\beta$-lactamases ($M{\beta}Ls$) are clinically significant enzymes which readily hydrolyze most $\beta$-lactam antibiotics. Discovering potential inhibitors for the $M{\beta}Ls$ is an expensive, time consuming endeavor. Virtual screening can sieve out inhibitor candidates with incompatible features prior to synthesis, decreasing these costs. Using Autodock 4.0, the binding locations and energies of four previously-studied potential inhibitors and four additional compounds obtained from the National Cancer Institute (NCI) database were computationally calculated. Based on the docking models of these eight compounds, we then designed several hypothetical inhibitor structures, compounds A through F, and performed their respective docking experiments. The docking results for compound F showed that it binds to the zinc containing active sites with a lowest predicted binding energy of -6.70 kcal/mol, suggesting F is the most likely potential $M{\beta}L$ inhibitor.

• Biomolecules & Therapeutics
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• 제1권1호
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• pp.26-30
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• 1993

Strain of treptomyces minoensis DMCJ-144 was tried to be improved so that it produces much more the $\alpha$-amylase inhibitor. Streptomyces minoensis DMCJ-144 was treated with 1 mg/mι (pH 9.0) of N-methyl-N'-nitro-N-nitrosoguanidine at $30^{\circ}C$ for 60 min and irradiated with UV light distanced 30 cm for 20 min. After mutagenesis, surviving colonies were cultured on the CM contaning acriflavine ($10{\mu}g/ml$) three times in order to enhance the mutability. And then through multi-level screening, colonies that ${\alpha}$-amylase inhibitor productibility. was Improved were selected by modified-blue value method. After third acriflavine treatment, $\alpha$-amylase inhibitory activities of selected colonies were found to be much better as compared with that of parent strain. One mutant strain showed 5.4 time inhibitory activity than the parent strain.