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Antitumor Activities of Lipophilic Nucleoside 5′-monophosphate Analogues as Prodrugs (Prodrug로서 지질친화성 Nucleoside 5′-(3-pyridinyl carbonyl) monophosphate 유도체의 항암 활성)

  • Lee, Bong-Hun;Park, Jang-Su;Kang, Shin-Won
    • Journal of Life Science
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    • v.9 no.1
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    • pp.58-62
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    • 1999
  • Several nucleoside 5'-monophosphate analogues and lipophilic nucleoside 5'-(3-pyridinylcarbonyl)monophosphate analogues were synthesized. Antitumor activities of the synthesized nucleoside malogues against P338 mouse leukemia, FM3A murine mammary carcinoma, and U937 human histiocytic lymphoma cells were determined by MTT assay. Antitumor activities of the lipophilic uridine 5'-(3-pyridinylcarbonyl) monophosphate(7) and 2',3'-didehydro-3'-deoxy-thymidine-5'-(3-pyridinylcarbonyl) monophosphate(8) were stronger than those of uridine 5'-monophosphate(1) and 2',3'-didehydro-3'-deoxythymidine-5'-monophosphate(4). This preliminary experimental result suggests that nucleoside 5'-(3-pyridinylcar-bonyl)monophosphate analogues may be new prodrugs to overcome the clinical limit.

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Enhanced Liver Targeting by Synthesis of $N_{\b{1}}-Stearyl-5-Fu$ and Incorporation into Solid lipid Nanoparticles

  • Yu, Bo-Tao;Xun-Sun;Zhang, Zhi-Rong
    • Archives of Pharmacal Research
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    • v.26 no.12
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    • pp.1096-1101
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    • 2003
  • To enhance the liver targeting and reduce the side effects of 5-fluorouracil (5-Fu), it was acylated by stearyl chloride to obtain .$\b{N}_{\b{1}}$stearyl-5-Fu (5-FuS). The chemical structure of the prodrug was confirmed by Nuclear Magnetic Resonance and Infrared Spectrometry. 5-FuS was incorporated into solid lipid nanoparticles (SLN), which were prepared by the physical agglomeration method. The mean diameter of 5-FuS-SLN was 240.19 nm and the drug loading was 20.53%. The release characteristics in vitro of 5-FuS-SLN were fitted to the first-order pharmacokinetic model. Compared with 5-Fu injection, a study on the distribution of 5-FuS-SLN in mice showed that 5-FuS-SLN could double 5-Fu concentration in mice livers. The main pharmacokinetic parameters of 5-FuS-SLN in rabbits is shown as follows: $V_d$=0.04336L/kg, $T_{1/2} \beta$=1.2834h, CL=0.1632 L/h. In conclusion, 5-FuS-SLN has significant liver targeting properties. The employment of a prodrug to enhance drug liposoluble properties and the preparation method presented in this paper, seem to be an alternative strategy to the traditional colloidal delivery system.

Investigation on the Structural, Electrical and Magnetic Properties of Layered Perovskite Manganite La0.5Sr1.5Mn0.5Cr0.5-xFexO4 (x=0.15, 0.3) System (층상 페로브스카이트 구조인 La0.5Sr1.5Mn0.5Cr0.5-xFexO4 (x=0.15, 0.3) 망가나이트의 구조적, 전기적, 자기적 특성의 연구)

  • Singh, Devinder
    • Journal of the Korean Chemical Society
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    • v.55 no.4
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    • pp.697-702
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    • 2011
  • The new layered perovskite manganites $La_{0.5}Sr_{1.5}Mn_{0.5}Cr_{0.5-x}Fe_xO_4$ (x=0.15, 0.3) have been prepared by standard ceramic method. The powder X-ray diffraction studies show that the phases crystallize with tetragonal unit cell in the space group I4/mmm. The electrical transport properties suggest that the phases show insulating behaviour and the electrical conduction in the phases occurs by a 3D variable range hopping mechanism. The magnetic properties suggest that both the phases are antiferromagnetic.

Effects of '5&6 Smoking Cessation Program' and 5-day Smoking Cessation Program' on adolescents' smoking behavior (5&6 금연프로그램과 5일 교실 금연프로그램의 청소년 금연효과)

  • Lim, Eun-Sun
    • Korean Journal of Health Education and Promotion
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    • v.27 no.2
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    • pp.95-108
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    • 2010
  • Objectives: The Purpose was to investigate the effects of the '5&6 smoking cessation program' and '5 days smoking cessation program' on the high school student's perception, urine cotinine, and smoking behaviors. Methods: This study was designed using nonequivalent control group pretest-posttest. The '5&6 smoking cessation program' was applied to the experimental group 1(28 students). The '5 days smoking cessation program' was applied to the experimental group 2(19 students). Control group was 53 students. Data was analyzed using descriptive statistics, $X^2$-test, Fisher's exact test, Independent-sample t-test, Paired t-test, ANOVA, Wilcoxon signed ranks test, Cronbach's coefficient alpha. Results: The '5&6 program' was significantly increased on smoking self-efficacy, stage of smoking cessation behavior change, Cons. for smoking and significantly decreased on daily smoking amount, urine cotinine level than control group. The '5 days program' was significantly decreased on urine cotinine level and Pros. for smoking than control group. The '5&6 program' was significantly increased on stage of smoking cessation behavior change than '5 days program'. Conclusion: This study showed that the '5&6 program and the '5 days program' are effective in adolescent's smoking cessation behaviors.

Improved Uniformity of Resistive Switching Characteristics in Ge0.5Se0.5-based ReRAM Device Using the Ag Nanocrystal (Ag Nanocrystal이 적용된 Ge0.5Se0.5-based ReRAM 소자의 Uniformity 특성 향상에 대한 연구)

  • Chung, Hong-Bay;Kim, Jang-Han;Nam, Ki-Hyun
    • Journal of the Korean Institute of Electrical and Electronic Material Engineers
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    • v.27 no.8
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    • pp.491-496
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    • 2014
  • The resistive switching characteristics of resistive random access memory (ReRAM) based on amorphous $Ge_{0.5}Se_{0.5}$ thin films have been demonstrated by using Ti/Ag nanocrystals/$Ge_{0.5}Se_{0.5}$/Pt structure. Ag nanocrystals (Ag NCs) were spread on the amorphous $Ge_{0.5}Se_{0.5}$ thin film and they played the role of metal ions source. As a result, comparing the conventional Ag/$Ge_{0.5}Se_{0.5}$/Pt structure, this Ti/Ag NCs/$Ge_{0.5}Se_{0.5}$/Pt ReRAM device exhibits the highly uniform bipolar resistive switching (BRS) characteristics, such as the operating voltages, and the resistance values. At the same time, a stable DC endurance(> 100 cycles), and the excellent data retention (> $10^4$ sec) properties were found from the Ti/Ag NCs/$Ge_{0.5}Se_{0.5}$/Pt structured ReRAM device.

Synthesis of Hydroxylactams and Esters Derived from Thalidomide and Their Antitumor Activities

  • Sun, Guanglong;Liu, Xiangchao;Zhou, Heng;Liu, Zenglu;Mao, Zhenmin
    • Bulletin of the Korean Chemical Society
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    • v.35 no.5
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    • pp.1337-1342
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    • 2014
  • A novel and convenient route for the synthesis of a series of thalidomide derivatives is described. Compound 2 was cyclized with different amines under alkaline condition to obtain 4-nitro substituted phthalimidines 3a-d. Hydroxylactams 4a-d were produced via bromination and hydroxylation. Different acyl chlorides were reacted with hydroxylactams to provide the desired esters 5a-d. All compounds were evaluated by MTT assay for their inhibitory activities against HCT-116, MG-63, MCF-7, HUVEC and HMVEC cell lines in vitro. Most of them showed no obvious cytotoxic effect on normal human cells, compounds 4a-d, $5a_2$, $5a_4$, $5a_5$, $5b_2$, $5c_2$ and $5d_2$ exhibited potent antitumor activities, among which compounds $5a_2$ and $5b_2$ were more effective than 5-FU.

Quantitative analysis of 5-HMF produced from fructose (과당에서 전환된 5-HMF(5-hydroxymethylfurfural)의 정량적 분석)

  • Sim, Jaehoon;Shin, Soo-Jeong
    • Journal of Korea Technical Association of The Pulp and Paper Industry
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    • v.45 no.1
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    • pp.27-34
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    • 2013
  • Quantitative analysis of 5-hydroxymethylfufural (5-HMF) conversion from fructose by dehydration and rearrangement was investigated by $^1H$-NMR spectroscopic method. Fructose was converted to 5-HMF in dimethylsulfoxide (DMSO)-$d^6$ or acidic deuterium hydroxide at controlled reaction temperature and time. With addition of internal standards (biphenyl for DMSO-$d^6$ solvent, and 2,5-dihydroxybenzoic acid for deuterium oxide solvent), conversion from fructose to 5-HMF was analyzed by $^1H$-NMR spectroscopy. Quantitative analysis was run by comparison with peak area integration between of 5-HMF and internal standard. In DMSO solvent, 5-HMF was stable end product but part of 5-HMF was converted to formic and levulinic acid at acidic aqueous medium.

안전감압계통의 열수력과도현상 평가

  • 이희도;윤선홍;박군철
    • Proceedings of the Korean Nuclear Society Conference
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    • 1996.05b
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    • pp.186-192
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    • 1996
  • 가압기의 유체 조건이 증기에서 이상유체로 변화하는 완전급수상실사고 경우에 대한 안전감압계통의 가압기 노즐 및 밸브 전단에서의 유량, 밸브 후단에서의 압력 변화 등 RELAP5/MOD1과 RELAP5/MOD3로 계산된 열수력 조건이 유사한 추세를 나타내었다. 또한 RELAP5/MOD1-CALPLOTFIII와 RELAP5/MOD3-CALPLOTFIII 전산체제로 계산된 안전감압계통의 각 배관부위에서의 동하중도 유사한 추세를 나타내었다. 즉, RELAP5/MOD1-CALPLOTFIII와 RELAP5/MOD3-CALPLOTFIII 전산체제를 이용한 안전감압계통의 열수력 과도현상 해석 결과가 유사하여 RELAP5/MOD1 대신에 RELAP5/MOD3가 안전감압계통의 열수력 과도현상 분석에 대체사용될 수 있을 것으로 판단된다. 그러나 본 연구는 안전감압계통에 국한하여 수행되었으며, RELAP5/MOD1과 RELAP5/MOD3를 이용한 가압기안전밸브 방출배관에 대한 기존의 연구 결과에 의하면 RELAP5/MOD3가 만족스러운 곁과를 제공하지 못하는 바, 다른 계통에 RELAP5/MOD1 대신 RELAP5/MOD3를 대체적용하기 위해서는 개별적으로 각 계통에 대한 비교 평가가 선행되어야 할 것으로 판단된다.

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5-Arylidene-2(5H)-Furanone Derivatives: Synthesis and Structure-Activity Relationship for Cytotoxicity

  • Bang, Seong-Cheol;Kim, Yong;Yun, Mi-Young;Ahn, Byung-Zun
    • Archives of Pharmacal Research
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    • v.27 no.5
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    • pp.485-494
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    • 2004
  • Thirty-eight 5-arylidene-2(5H)-furanone derivatives possessing halo-, methoxy-, oxo-, dioxo-, and thiophenyl groups as well as anthraquinone and naphthquinone moieties were synthesized, and their cytotoxicity was evaluated against various cancer cell lines. The introduction of halogen atoms or nitro group at aromatic ring of 5-arylidene-2(5H)-furanone was shown to increase the cytotoxicity with 5-(3-nitrobenzylidene )-2(5H)-furanone (21) being the most potent. Among anthracenyl or naphthalenyl derivatives, (E)-5-[2-(1 ,4-dimethoxy-9, 10-dioxo) anthracenyl]-2(5H)-furanone (34) showed the most potent cytotoxic activity.

Synthesis and Structure-activity Relationship of Cytotoxic $5,2^I,5^I$-Trihydroxy-7,8-dimethoxyflavanone Analogues

  • Min, Byung-Sun;Ahn, Byung-Zun;Bae, Ki-Hwan
    • Archives of Pharmacal Research
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    • v.19 no.6
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    • pp.543-550
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    • 1996
  • Analogues of $2(S)-5, 2^{l}, 5^{l}$-trihydroxy-7, 8-dimethoxyflavanone, a naturally-occurring compound, which had been reported to have potent antitumor activity, were synthesized and examined for the cytotoxicity against three cancer cell lines. Among the intermediate chalcones and synthetic 5-hydroxy-7, 8-dimethoxyflavanone analogues, $({\pm})2^{l}, 5^{l}-dibenzyloxy-5, 7, 8-trimethoxyflavanone$ exhibited about 2-8 times stronger activity than $2(S)-5, 2^{l}, 5^{l}$-trihydroxy-7, 8-dimethoxyflavanone against L1210, K562 and A549 cancer cell lines. In the structure-activity relationship, it is suggested that among analogues of 5-hydroxy-7, 8-dimethoxyflavanone, the existence of two oxygenated groups of para-relation at $C-2^{I} and C-5^{I}$ positions on flavanone B-ring, may be necessary to exhibit effective cytotoxic activity.

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