• Bulletin of the Korean Chemical Society
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• 제27권11호
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• pp.1769-1774
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• 2006

A new liquid chromatographic chiral stationary phase based on (2S,3S)-O,O'-bis-(10-undecenoyl)-N,N'-bis-(3,5-dinitrobenzoyl)-2,3-diamino-1,4-butandiol was prepared starting from (2R,3R)-1,4-bis(benzyloxy)-2,3-butanediol. The new chiral stationary phase was applied to the resolution of racemic anilide derivatives of N-acetyl-a-amino acids, 1,1'-bi-2-naphthol and 3,3'-diaryl-1,1'-bi-2-naphthols. The CSP was also applied to the resolution of some chiral drugs including a diuretic, bendroflumethiazide, and non-steroidal anti-inflammatory agents such naproxen and alminoprofen. In every case, the chiral recognition efficiency of the new CSP was quite excellent.

• 한국정보통신학회논문지
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• 제10권11호
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• pp.2039-2044
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• 2006

생물정보는 사람의 능력을 넘어 섰으며 데이터 마이닝과 같은 인공지능기법이 필수적으로 요구된다. 한번에 수천 개의 유전자 발현 정보를 획득할 수 있는 DNA마이크로어레이 기술은 대량의 생물정보를 가진 대표적인 신기술로 질병의 진단 및 예측에 있어 새로운 분석방법들과 연계하여 많은 연구가 진행 중이다. 이러한 새로운 기술들을 이용하여 유전자의 메 커니즘을 규명하는 것은 질병의 치료 및 신약의 개발에 많은 도움을 줄 것으로 기대 된다. 본 논문에서는 마이크로어레이 실험에서 다양한 원인에 의해 발생하는 잡음(noise)을 줄이 거나 제거하는 과정인 표준화과정을 거쳐 표준화 방법들의 성능 비교를 위해 특징 추출방법 인 베이지안(Bayesian) 방법을 이용하여 마이크로어레이 데이터의 분류 정확도를 비교 평가하여 Lowess 표준화 후 95.89%로 분류성능을 향상시킬 수 있음을 보였다.

• 대한화장품학회지
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• 제34권1호
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• pp.15-23
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• 2008

본 연구는 유용성 물질 포집에 효과적인 solid lipid nanoparticle(SLN)을 이용하여 수용성물질인 LA-PEG을 새로운 제조방법에 응용하여 실험하였다. 지질로 사용된 오일은 coconut oil, macadamia oil, 그리고 jojoba oil 3가지로 이들의 특징은 생분해성이 강하다. 외부유화제로는 Tween 20, Tween 60을 이용하여 T-SLN을 제조하였으며, SLN의 입자 분포를 비교 분석한 결과 coconut oil을 지질로 하여 사용한 것이 크기가 가장 작았으며 사용한 계면활성제의 양에 따라 입자크기와 분포형태가 달라졌다. 1%의 Tween 60과 macadamia oil을 이용한 베이스가 입자크기가 가장 컸다. 방출관찰결과 coconut oil을 지질로 한 2%의 Tween 20의 베이스가 가장 늦게 방출되었고, 가장 빠른 방출한 것은 Tween 60 2% 베이스였다.

• 한국어병학회지
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• 제9권2호
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• pp.185-193
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• 1996

지금까지 사용해온 많은 항균제들에 대한 내성의 획득은 어병세균의 박멸을 어렵게 만드는 심각한 문제를 야기하고 있다. 이 연구에서는 최근 인간의 세균성 질병치료 목적으로 사용하기 시작하거나 개발중인 new quinolone계 약물 14종을 대상으로 군산근교와 뱀장어(Anguilla japonica) 양만장 사육수에서 분리한 75종의 Edwardsiella tarda균에 대한 항균활성을 측정함으로써 장래의 신규 수산용 항균제 개발에 필요한 정보를 얻고자 시도하였다. Broth dilution assay에 의해 측정한 in vitro 항균활성시험에서 DU-6859는 $MIC_{50}$ 값 $0.05{\mu}g$/ml로 가장 강력한 약효를 보여주었다. $MIC_{50}$값 0.2-$0.78{\mu}g$/ml의 범위에 드는 약물들인 T-3762, Bay-y3118, ciprofloxacin, norfloxacin, ofloxacin 및 tosufloxacin은 그 다음으로 강력한 약물군을 형성하였다. 한편 difloxacin, sparfloxacin, fleroxacin, Q-35, amifloxain, lomefloxacin 및 enoxain 등은 약효가 약한 약물들로서 $MIC_{50}$값이 1.56-$3.13{\mu}g$/ml 범위에 속하였다. 이들 항균제에 대해서 내성(MIC 값이 $v$/ml 이상으로 정하였을 때)을 가지고 있는 균수는 T-3762 및 Bay-y3118은 3주, norfloxacin은 5주, tosufloxacin 12주, ciprofloxacin 및 ofloxacin 13주, sparfloxacin 16주, fleroxacin 19주, amifloxacin 및 lomefloxacin 31주, Q-35 36주, enoxacin 41주, difloxacin 44주로 각각 나타났다. DU-6859의 경우에는 내성이 있는 균주가 전혀 발견되지 않았다. 이 연구 결과들은 new quinolone계 약물들 사이에도 Edwardsiella tarda균에 대한 항균활성이 다양함을 시사하며 또한 향후 항균제 도입에 중요한 참고자료로 이용될 수 있을 것이다.

• 한국식품영양학회지
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• 제22권2호
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• pp.252-260
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• 2009

According to Article 7 and Annex B of the World Trade Organization(WTO) Agreement on the Application of Sanitary and Phytosanitary(SPS) Measures, WTO members are required to notify their newly established or amended SPS measures that might affect international trade. This study analyzed SPS notifications from 1995 to 2008 to identify international trends for food safety measures. The notifications were collected from the SPS information management system and the official document distribution system of WTO. The 153 WTO members represented 37 developed countries, 84 developing countries and 32 least developed countries. The number of overall notifications was 9,820. The annual notifications increased from 198 in 1995 to 1,264 in 2008. The monthly average notifications were from 44.8 in December to 69.5 in June; however, there were no statistical differences among them. The six leading Members in terms of notification submissions were United States(U.S.), Brazil, New Zealand, Canada, European Community and Korea. Among the regular and emergency notifications, 62.7% notifications were concerned with food safety, followed by animal and plant protections. Among animal protection notifications, 54.8% were emergency situations. Of the 4,821 food safety notifications, 60.4% were from developed countries, and 39.3% were from developing countries. Measures concerning pesticide residues and risk assessments were mainly from developed countries. In contrast, 77.5% of the measures concerning zoonoses were from developing countries. However considering the numbers of developing and developed countries, the average number of measures for each country was similar. Food safety measures were mainly involved pesticide residues followed by food additives, zoonoses, new regulations, labeling. As the overall notifications, zoonosis measures were mainly emergency notifications. Measures concerning pesticide residues, food additives, zoonoses, new regulations, veterinary drugs, and labeling were submitted most often by the U.S., Korea, Albania, U.S., Australia, and U.S., respectively. Identifying the exact trends of food safety measures was complicated by a number of factors. However, WTO notifications might be useful tool in providing a general view of international trends.

• Biomolecules & Therapeutics
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• 제21권3호
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• pp.190-195
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• 2013

Cisplatin is a member of platinum-containing anti-cancer drugs that causes cross-linking of DNA and ultimately cancer cell apoptosis. The therapeutic function of cisplatin on various types of cancers has been widely reported but the side effects have been discovered together and nephrotoxicity has been regarded as major side effect of cisplatin. To select candidates for new sensitive nephrotoxicity biomarker, we performed proteomic analysis using 2-DE/MALDI-TOF-MS followed by cisplatin treatment in human kidney cell line, HK-2 cells, and compared the results to the gene profile from microarray composed of genes changed in expression by cisplatin from formerly reported article. Annexin A5 has been selected to be the most potential candidate and it has been identified using Western blot, RT-PCR and cell viability assay whether annexin A5 is available to be a sensitive nephrotoxic biomarker. Treatment with cisplatin on HK-2 cells caused the increase of annexin A5 expression in protein and mRNA levels. Over-expression of annexin A5 blocked HK-2 cell proliferation, indicating correlation between annexin A5 and renal cell toxicity. Taken together, these results suggest the possibility of annexin A5 as a new biomarker for cisplatin-mediated nephrotoxicity.

• Bulletin of the Korean Chemical Society
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• 제34권11호
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• pp.3429-3443
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• 2013

Chemokine receptor (CCR2) is a G protein-coupled receptor that contains seven transmembrane helices. Recent pharmaceutical research has focused on the antagonism of CCR2 and candidate drugs are currently undergoing clinical studies for the treatment of diseases like arthritis, multiple sclerosis, and type 2 diabetes. In this study, we analyzed the time dependent behavior of CCR2 docked with a potent 4-azetidinyl-1-aryl-cyclohexane (4AAC) derivative using molecular dynamics simulations (MDS) for 20 nanoseconds (ns). Homology modeling of CCR2 was performed and the 4AAC derivative was docked into this binding site. The docked model of selected conformations was then utilized to study the dynamic behavior of the 4AAC enzyme complexes inside lipid membrane. MDS of CCR2-16b of 4AAC complexes allowed us to refine the system since binding of an inhibitor to a receptor is a dynamic process and identify stable structures and better binding modes. Structure activity relationships (SAR) for 4AAC derivatives were investigated and reasons for the activities were determined. Probable binding pose for some CCR2 antagonists were determined from the perspectives of binding site. Initial modeling showed that Tyr49, Trp98, Ser101, Glu291, and additional residues are crucial for 4AAC binding, but MDS analysis showed that Ser101 may not be vital. 4AAC moved away from Ser101 and the hydrogen bonding between 4AAC and Ser101 vanished. The results of this study provide useful information regarding the structure-based drug design of CCR2 antagonists and additionally suggest key residues for further study by mutagenesis.

• Journal of Pharmaceutical Investigation
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• 제34권3호
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• pp.161-168
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• 2004

5-Fluorouracil (5-FU) is an antimetabolite anticancer agent active against many types of solid tumors. Tegafur (TF), a prodrug of 5-FU, is frequently used in combination with uracil as dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine. We studied the stability of 5-FU and TF in biological fluids of rats and determined their bioavailability (BA) and excretion into bile, and urine. The drug concentrations were analyzed by an HPLC method. At room temperature, there was a 14-30% decrease in the concentration of 5-FU and TF in bile, urine, and plasma specimen at 10 and $100\;{\mu}g/ml$ over 240 min. No significant difference was noted among the sample types or between two different concentrations of 10 and $100{\mu}g/ml$. The decrease in drug concentration was significantly less in samples kept on ice (6-12%) for both drugs. These data indicate that biological fluid samples containing 5-FU or TF in plasma, urine, or bile should be placed on ice during the sample collection. Following these storage guidelines, samples were collected after administration 50 mg/kg of each drug via i.v. or oral route. BA was 1.5 folds greater for TF (60%) than that of 5-FU (42%). Approximately 0.52 and 3.3% of the i.v. doses of 5-FU and TF was excreted into bile, respectively. Renal clearance of 5-FU was about 16% of its total body clearance. These results suggest that instability of 5-FU and TF in biological fluids should be considered in pharmacokinetic or pharmacogenomic studies.

• Archives of Pharmacal Research
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• 제29권1호
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• pp.26-33
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• 2006

Some new derivatives of 1,2,4-triazolo[2,3-a]benzimidazoles were synthesized through the reaction of 1,2-diaminobenzimidazole with carbon disulfide. The resulting 1,2,4-triazolo-[2,3a]benzimidazole-2-thione intermediate was reacted with one equivalent of alkyl halides to give the corresponding 2-alkylthio derivatives, which were further alkylated through the reaction with another one equivalent of different alkyl halides to afford the target compounds; 1-alkyl-2alkylthio-1,2,4-traizolo[2,3-a]benzimidazoles. On the other hand, the 1,2-disubstituted derivatives with two identical alkyl substituents were prepared by the reaction of 1,2,4-triazolo[2,3-a]benzimidazole-2-thione with two equivalents of the alkyl halides. The structures of the new compounds were assigned by spectral and elemental methods of analyses. The synthesized compounds were tested for their antibacterial and antifungal activities. Most of the tested compounds proved comparable results with those of ampicillin and fluconazole reference drugs. The study indicated that, the antibacterial as well as the antifungal activities of the test compounds were improved with increase in the bulkiness of the introduced alkyl groups. Also, some active antibacterial compounds were tested for their antimycobacterial activity. All the test compounds showed equipotent antitubercular activity as that of INH as a reference drug.

• Archives of Pharmacal Research
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• 제28권7호
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• pp.848-853
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• 2005

Synurus deltoides was previously found to possess significant anti-inflammatory activity especially against chronic inflammation, and strong analgesic activity in vivo. In this study, new anti-inflammatory formulation containing S. deltoides extract as a major ingredient was prepared and in vivo activity was evaluated. The plausible action mechanism was also investigated. The new formulation (SAG) contains 1 part of S. deltoides extract, 0.9 part of Angelica gigas extract and 0.9 part of glucosamine sulfate (w/w). SAG inhibited dose-dependently edematic response of arachidonic acid (AA)- and 12-O-tetradecanoyl 13-acetate (TPA)-induced ear edema in mice, which is an animal model of acute inflammation. SAG showed 44.1 % inhibition of AA-induced ear edema at an oral dose of 50 mg/kg. In an animal model of chronic inflammation, SAG clearly reduced the edematic response of 7 -day model of multiple treatment of TPA (38.1 % inhibition at 200 mg/kg/day). Furthermore, SAG (50-800 mg/kg/day) as well as S. deltoides extract (285 mg/kg/day) significantly inhibited prostaglandin $E_2$ production from the skin lesion of the animals of 7-day model. These results were well correlated with in vitro finding that SAG as well as S. deltoides extract reduced cyclooxygenase (COX)-1- and COX-2-induced prostanoid production, measured in mouse bone marrow-derived mast cells. Therefore, these results suggest that SAG possesses anti-inflammatory activity in vivo against acute as well as chronic inflammatory animal models at least in part by inhibition of prostaglandin production through COX-1/COX-2 inhibition. And COX inhibition of SAG is possibly contributed by S. deltoides extract among the ingredients. Although the anti-inflammatory potencies of SAG were less than those of currently used anti-inflammatory drugs, this formulation may have beneficial effect on inflammatory disorders as a neutraceutical.