• 약학회지
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• 제48권2호
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• pp.141-146
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• 2004

Selective COX-2 inhibitors were expected to retain anti-inflammatory activity by inhibition of prostaglandin production with reduction of gastric and renal side effect associated with non-steroidal anti-inflammatory drugs. This study reported the syntheses of novel 2-thiohydantoin and hydantoin derivatives which have the structure of 5-membered heterocyclic ring substituted with two aryl groups, phenyl group at 5-position and p-sulfamylphenyl or p-methoxyphenyl group at 1-position. These synthetic compounds showed significant COX-2 activities in vitro screening. Among them, 5-phenyl-2-thiohydantoin and hydantoin substituted with benzyl group at 3-position, compounds 5 and 8, could be considered as lead compounds with $IC_{50}$/=13.13∼18.78 $\mu\textrm{g}$/$m\ell$ for the development of COX-2 inhibitors.

• 생약학회지
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• 제28권3호
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• pp.131-137
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• 1997

The aqueous and methanolic extracts of 110 crude drugs were screened for hyaluronidase inhibitory activity using a microplate assay. Among them, MeOH extract of 15 crude drugs inhibited more than 80% of hyauluronidase activity at the concentration of 5mg/ml. The active principles of Anemarrhenae Rhizoma, Rhei Rhizoma, Ephedrae Herba, Pteropi Faeces and Ginseng Radix alba were transferred into organic solvents.

• Bulletin of the Korean Chemical Society
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• 제32권5호
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• pp.1645-1649
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• 2011

[ ${\beta}$ ]Ketoacyl acyl carrier protein synthase I (KAS I) is involved in the elongation of unsaturated fatty acids in bacterial fatty acid synthesis and a therapeutic target of designing novel antibiotics. In this study, we performed receptor-oriented pharmacophore-based in silico screening of E. coli KAS I (ecKAS I) with the aim of identifying novel inhibitors. We determined one pharmacophore map and selected 8 compounds as candidates ecKAS I inhibitors. We discovered one antimicrobial compound, YKAe1008, N-(3-pyridinyl) hexanamide, displaying minimal inhibitory concentration (MIC) values in the range of 128-256 ${\mu}g/mL$ against MRSA and VREF. YKAe1008 was subsequently assessed for binding to ecKAS I using saturation-transfer difference NMR spectroscopy. Further optimization of this compound will be carried out to improve its antimicrobial activity and membrane permeability against bacterial cell membrane.

• Journal of Microbiology and Biotechnology
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• 제23권6호
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• pp.779-784
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• 2013

Leptospirosis is a worldwide zoonosis of global concern caused by Leptospira interrogans. The availability of ligand libraries has facilitated the search for novel drug targets using chemogenomics approaches, compared with the traditional method of drug discovery, which is time consuming and yields few leads with little intracellular information for guiding target selection. Recent subtractive genomics studies have revealed the putative drug targets in peptidoglycan biosynthesis pathways in Leptospira interrogans. Aligand library for the murD ligase enzyme in the peptidoglycan pathway has also been identified. Our approach in this research involves screening of the pre-existing ligand library of murD with related protein family members in the putative drug target assembly in the peptidoglycan biosynthesis pathway. A chemogenomics approach has been implemented here, which involves screening of known ligands of a protein family having analogous domain architecture for identification of leads for existing druggable protein family members. By means of this approach, one murC and one murF inhibitor were identified, providing a platform for developing an anti-leptospirosis drug targeting the peptidoglycan biosynthesis pathway. Given that the peptidoglycan biosynthesis pathway is exclusive to bacteria, the in silico identified mur ligase inhibitors are expected to be broad-spectrum Gram-negative inhibitors if synthesized and tested in in vitro and in vivo assays.

• Journal of Microbiology and Biotechnology
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• 제32권6호
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• pp.718-729
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• 2022

Esophageal squamous cell carcinoma (ESCC) is the most common primary esophageal malignancy with poor prognosis. Here, due to the necessity for exploring potential therapies against ESCC, we obtained the gene expression data on ESCC from the TCGA and GEO databases. Venn diagram analysis was applied to identify common targets. The protein-protein interaction network was constructed by Cytoscape software, and the hub targets were extracted from the network via cytoHubba. The potential hub nodes as drug targets were found by pharmacophore-based virtual screening and molecular modeling, and the antitumor activity was evaluated through in vitro studies. A total of 364 differentially expressed genes (DEGs) in ESCC were identified. Pathway enrichment analyses suggested that most DEGs were mainly involved in the cell cycle. Three hub targets were retrieved, including CENPF, CCNA2 (cyclin A), and CCNB1 (cyclin B1), which were highly expressed in esophageal cancer and associated with prognosis. Moreover, amentoflavone, a promising drug candidate found by pharmacophore-based virtual screening, showed antiproliferative and proapoptotic effects and induced G1 in esophageal squamous carcinoma cells. Taken together, our findings suggested that amentoflavone could be a potential cell cycle inhibitor targeting cyclin B1, and is therefore expected to serve as a great therapeutic agent for treating esophageal squamous cell carcinoma.

• Archives of Pharmacal Research
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• 제25권6호
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• pp.817-819
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• 2002

In the course of screening Korean natural products for acetylcholinesterase (AChE) inhibitory activity, it was found that a methanolic extract of the aerial parts of Corydalis incisa (Papaveraceae) showed significant inhibitory effects on AChE. Corynoline isolated from this plant inhibited AChE activity in a dose-dependent manner, and the $IC_{50}$ value of corynoline was $30.6{\;}{\mu}M$. The AChE inhibitory activity of corynoline was reversible and noncompetitive.

• 한국수산학회:학술대회논문집
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• 한국수산학회 2005년도 춘계학술대회
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• pp.213-214
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• 2005

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2005년도 생물공학의 동향(XVII)
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• pp.635-636
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• 2005

• 농약과학회지
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• 제5권3호
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• pp.41-46
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• 2001

분지아미노산 생합성 과정에 관여하는 첫 번째 효소인 acetolactate synthase (ALS)를 대상으로 수행할 수 있도록 고효율 검색방법(High Throughput Screening, HTS)을 개발하였고, 이를 이용하여 식물특이적 효소 저해제로 알려진 107개의 기존 화합물 중에서 새로운 ALS 저해 화합물을 선발하였다. 기존의 방법과 비교할 경우 한사람이 1회 수행한다고 하면 8 배 효율이지만 연속적으로 수행한다고 할 경우 1/10 이하의 양, 동일한 재료의 적용, 측정 결과의 계산, enzyme kinetics 등을 감안하면 최소 100 배 이상의 효과를 얻을 수 있다. 새로운 ALS 저해제로 탐색된 화학물질은, ammooxyacetic acid, azelaic acid, citric acid, cyanuric fluoride, glyoxylic acid, itaconic acid, malonic acid, niclosamid, oxalic acid, 2-oxoglutaric acid, suramin 등이었다. 앞으로 이들을 기본 구조로 하여 신규 ALS 저해 제초제의 개발을 위한 유도체의 합성에 이용되었으면 한다.

• Journal of Microbiology and Biotechnology
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• 제33권3호
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• pp.329-338
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• 2023

Enterohemorrhagic Escherichia coli (EHEC) is a foodborne pathogen that produces attaching and effacing lesions on the large intestine and causes hemorrhagic colitis. It is primarily transmitted through the consumption of contaminated meat or fresh produce. Similar to other bacterial pathogens, antibiotic resistance is of concern for EHEC. Furthermore, since the production of Shiga toxin by this pathogen is enhanced after antibiotic treatment, alternative agents that control EHEC are necessary. This study aimed to discover alternative treatments that target virulence factors and reduce EHEC toxicity. The locus of enterocyte effacement (LEE) is essential for EHEC attachment to host cells and virulence, and most of the LEE genes are positively regulated by the transcriptional regulator, Ler. GrlA protein, a transcriptional activator of ler, is thus a potential target for virulence inhibitors of EHEC. To identify the GrlA inhibitors, an in vivo high-throughput screening (HTS) system consisting of a GrlA-expressing plasmid and a reporter plasmid was constructed. Since the reporter luminescence gene was fused to the ler promoter, the bioluminescence would decrease if inhibitors affected the GrlA. By screening 8,201 compounds from the Korea Chemical Bank, we identified a novel GrlA inhibitor named Grlactin [3-[(2,4-dichlorophenoxy)methyl]-4-(3-methylbut-2-en-1-yl)-4,5-dihydro-1,2,4-oxadiazol-5-one], which suppresses the expression of LEE genes. Grlactin significantly diminished the adhesion of EHEC strain EDL933 to human epithelial cells without inhibiting bacterial growth. These findings suggest that the developed screening system was effective at identifying GrlA inhibitors, and Grlactin has potential for use as a novel anti-adhesion agent for EHEC while reducing the incidence of resistance.