• The Korean Journal of Pesticide Science
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• v.4 no.2
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• pp.29-31
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• 2000

New convenient and economical synthesis of 5,6-dihydro-2-methyl-1,4-oxathiin-3-carboxanilide 1 and the plausible reaction mechanism were described. Reaction of ${\alpha}$-chloroacetoacetanilide 4 (1 molar equivalent) with 2-mercaptoethanol (1.2 molar equivalent) in the presence of p-toluenesulfonic acid monohydrate (0.05 molar equivalent) as a catalyst in refluxing toluene with water trap yielded carboxin 1. The proposed mechanism is that ${\alpha}$-chloro 1,3-oxathiolane 8 which is a heuithioketal of 4 was converted to unisolable sulfonium ion 9 through neighboring group participation of sulfur followed by rearrangement to more stable oxonium ion 12 and then release acidic proton to produce the carboxin 1.

• BMB Reports
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• v.37 no.4
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• pp.416-421
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• 2004

The antioxidant activities of NADH and of its analogue, 1,4-dihydro-2,6-dimethyl-3,5-dicarbethoxy-pyridine ($PyH_2$), were evaluated in vitro. NADH was found to be oxidized by the peroxyl radical derived from 2,2-azobis-(2-amidinopropane) dihydrochloride (AAPH) decomposition, in a pH-dependent manner. Both NADH and $PyH_2$ inhibited the peroxidation of egg yolk lecithin (EYL) liposomes, although $PyH_2$ was more effective than NADH when 2,2'-azobis-4-methoxy-2,4-dimethyl-valeronitrile (methoxy-AMVN) was employed to induce EYL liposome peroxidation. The antioxidant activities of NADH and $PyH_2$ were also evaluated by measuring their influences on 1,3-diphenylisobenzofuran (DPBF) fluorescence decay in the presence of peroxyl radicals. NADH and $PyH_2$ were much more effective at inhibiting DPBF quenching in Triton X-100 micelles than in liposomes. These results indicate that NADH can inhibit lipid peroxidation despite being hydrophilic. Nevertheless, membrane penetration is an important factor and limits its antioxidant activity.

• Archives of Pharmacal Research
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• v.22 no.6
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• pp.565-570
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• 1999

DW2282,(S)-(+)-4-phenyl-1-[1-(4-aminobenzoyl)-indoline-5-sulfonyl]-4,5-dihydro-2-imidazolone hydrochloride, is a new anticancer agent which is thought to exhibit a characteristic mechanism of action in the inhibition of tumor growth. In this study, we estimated the toxicities of DW2282 in mice. When mice were orally dosed for five consecutive days at the dosages of 50, 100 and 150 mg/kg, DW2282 did not induced methemoglobinemia and hypoglycemia at any of these doses. However, increased ALT and AST values were observed in the 150 mg/kg dosing group, and white blood cells (WBC) were significantly decreased at all doses. However, the changes in WBC count, ALT and AST immediately reversed after the cessation of drug administration. In addition, we found that DW2282 did not cause an increase in hemolysis in human blood. Taken together, these data suggested that DW2282 may have a relatively low level of toxicity, and that there may be a quick recovery from any toxicity it dose produce.

• Preventive Nutrition and Food Science
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• v.6 no.4
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• pp.230-234
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• 2001

The extract of Ulmus davidiana var. japonica cortex has known as natural anti-inflammatory substance in East Asia. For the identification of antimicrobial substance, it was extracted by using methanol and fractionated by using different organic solvents. The fraction of butanol was represented the highest antimicrobial activities. Therefore, the butanol fraction was purified and identified the chemical structure by $^1$H and $^{13}$ C-NMR spectra, FT-IR and EI/MS spectroscopies. The isolated antimicrobial substance was identified as cis-2-[3,4-dihydroxy phenyl]-3,4-dihydro-2H-1-benzopyran-3,5,7-triol, which has commonly known as (-)epicatechin. Its minimum inhibitory concentrations (MICs) against Staphylococcus aureus and Listeria monocytogenes were shown as 100 $\mu\textrm{g}$/mL, respectively.

• Korean Journal of Food Science and Technology
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• v.23 no.1
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• pp.68-75
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• 1991

The seed oil of Ternstroemia gymnanthera. a species of the Ternstroemiaceae, is mainly composed of triglyceride(92.4%), followed by polar lipids(5.9%), sterol(1.2%) and pigments(0.5%). This oil contains 4.8% of cis-11, 12-methylene octadecanoic acid(lactobacillic acid) in the fatty acid composition of the total oil. This identification is based on information from non-urea inclusion formation, silver nitrate impregnated silica gel column and gas liquid chromatography, $^1H-&\;^{13}C-nuclear$ magnetic resonance and mass spectroscopy. Smaller amounts(0.1%) of presumptive 9, 10-methylene hexadecanoic acid(dihydro malvalic acid) is also detected. The major fatty acids in this oil are C18 : 1(36.1%), C18: 2(30.9%), C16: 0(15.1%), C16: 1(7.6%) and C18: 0(3.4%).

• Archives of Pharmacal Research
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• v.28 no.8
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• pp.930-935
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• 2005

We have investigated the effects of relatively high concentration of carbachol (CCh), an agonist of muscarinic acetylcholine receptor (mAChR), on cardiac automaticity in mouse heart. Action potentials from automatically beating right atria of mice were measured with conventional microelectrodes. When atria were treated with $100{\mu}M$ CCh, atrial beating was immediately arrested and diastolic membrane potential (DMP) was depolarized. After exposure of the atria to CCh for $\~4 min$, action potentials were regenerated. The regenerated action potentials had lower frequency and shorter duration when compared with the control. When atria were pre-exposed to pirenzepine $(1{\mu}M)$, an $M_1$ mAChR antagonist, there was complete inhibition of CCh-induced depolarization of DMP and regeneration of action potentials. Pre-exposure to AFDX-116 (11 ({2-[(diethylamino)-methyl]-1-piperidyl}acetyl)-5, 11-dihydro-6H-pyridol[2,3-b][1,4] benzodiazepine-6-one base, $1{\mu}M$), an $M_2$ mAChR antagonist, failed to block CCh-induced arrest of the beating. However, prolonged exposure to CCh elicited gradual depolarization of DMP and slight acceleration in beating rate. Our data indicate that high concentration of CCh depolarizes membrane potential and recovers right atrial automaticity via $M_1$ mAChR, providing functional evidence for the role of $M_1$ mAChR in the atrial myocytes.

• Archives of Pharmacal Research
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• v.27 no.2
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• pp.239-245
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• 2004

KR-31543, (2S,3R,4S)-6-amino-4-[N-(4-chlorophenyl)-N-(2 -methyl-2H-tetrazol-5-ylmethyl) amino]-3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-2H-1-benzopyran, is a new neuroprotective agent for preventing ischemia-reperfusion damage. This study was performed to identify the metabolic pathway of KR-31543 in human liver microsomes and to characterize cytochrome P450 (CYP) enzymes that are involved in the metabolism of KR-31543. Human liver microsomal incubation of KR-31543 in the presence of NADPH resulted in the formation of two metabolites, M1 and M2. M1 was identified as N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine on the basis of LC/MS/MS analysis with a synthesized authentic standard, and M2 was suggested to be hydroxy-KR-31543. Correlation analysis between the known CYP enzyme activities and the rates of the formation of M 1 and M2 in the 12 human liver microsomes have showed significant correlations with testosterone 6$\beta$-hydroxylase activity (a marker of CYP3A4). Ketoconazole, a selective inhibitor of CYP3A4, and anti-CYP3A4 monoclonal antibodies potently inhibited both N-hydrolysis and hydroxylation of KR-31543 in human liver microsomes. These results provide evidence that CYP3A4 is the major isozyme responsible for the metabolism of KR-31543 to M1 and M2.

• Proceedings of the Korean Society for Food Science of Animal Resources Conference
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• 2005.10a
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• pp.196-203
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• 2005

축산식품 고기내의 잔류항생물질을 신속하고 간편하고 정확하게 분석하기 위한 시험법 개발 을 목적으로 하였다. 축산식품내의 일반적인 잔류항생물질에 대한 지금까지의 분석법으로는 Bioassay법, TLC법, ELISA법, GC법 및 HPLC법 등이 있지만 Streptomycin/Dihydro streptomycin, Neomycin에 대한 HPLC법은 거의 확립되어 있지 않은 실정이다. 우리나라의 공인 검사법으로는 Bioassay법 및 HPLC법 등이 있지만 그러나 지금까지의 방법으로는 검출감도가 낮은 것이 큰 문제점으로 되어 왔다. 본 연구에서는 DST에 대한 HPLC법에 대한 보고한 P. Edder 방법 중에 clean-up과정 및 이동상 조건을 대폭 수정하여 DST의 분리 및 검출감도를 낮추려고 시도하였다. 본 연구에 사용된 유도체화 장치 Post-Column Derivatization Instrument PCX 5100 (Pickering Laboratories, Inc.)의 컬럼온도는 $40^{\circ}C$, 오븐온도 $55^{\circ}C$, reagent 유속 0.6ml/min mobile phase 유속 0.8ml/min으로 검출기는 형광검출기를 이용하여 DST 검출에 대해 만족할 만한 결과를 얻었다. 이때의 분석소요시간은 약 15분이었다. 표준시료 DST의 검량선은 넓은 농도범위(0.02${\sim}$1.0ppm)에서 양호한 직선성을 나타냈다. 본 시험법에 의한 검출한계는 limit of detection (LOD)은 0.02ppm이었으며, 적어도 고기에서의 MRL이 0.6ppm임을 감안하면 DST를 정량적으로 정도 좋게 측정할 수 있다는 것을 확인했다. 상기의 조건하에서 실제시료인 고기에 표준 DST를 1ppm을 spiking한 후 SPE상에서 SCX(Strong cation exchange column)을 통한 clean-up과정을 거친 후의 DST의 limit of quantification(LOQ)는 약 0.47ppm이었으며, 이에 대한 회수율은 97.7%(n= 8)를 나타냈다. 실제 codex에서 권장한 고기의 MRL이 0.6ppm인 점을 감안하면 codex 권고치에 도달할 수 있는 것으로 판단되었다. 따라서 본 연구에서 개발된 시험법은 지금까지 국내적으로 DST에 대한 시험법이 확립되어 있지 않은 것으로 이와 아울러 간편한 parallux와 병용해 DST에 대한 정량 및 정성 분석을 유도체화 장치 및 형광검출기를 이용해 잔류항생물질 DST에 대한 분석시험법의 개발이 가능하다고 여겨진다.

• Journal of Life Science
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• v.18 no.11
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• pp.1499-1506
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• 2008

To examine antitumor activity of the edible plant Zanthoxylum schinifolium, the cytotoxic effect of various organic solvent extracts of its stems on human acute leukemia Jurkat T cells was investigated. Among these extracts such as methanol extract (SS-7), methylene chloride extract (SS-8), ethyl acetate extract (SS-9), n-butanol extract (SS-10), and residual fraction (SL-11), SS-8 exhibited the most cytotoxic activity against Jurkat T cells. The methylene chloride extract (SS-8) possessed the apoptogenic activity capable of inducing sub-G1 peak along with apoptotic DNA fragmentation in Jurkat T cells. Western blot analysis revealed that SS-8 induced apoptosis via mitochondrial cytochrome c release into cytoplasm, subsequent activation of caspase-9 and caspase-3, and cleavage of PARP, which could be blocked by overexpression of Bcl-xL. Jurkat T cell clone I2.1 $FADD^{-/-}$) and Jurkat T cell clone I9.2 (caspase-$8^{-/-}$ were as sensitive as was the wild-type Jurkat T cell clone A3 to the cytotoxic effect of SS-8, suggesting no contribution of Fas/FasL system to the SS-8-mediated apoptosis. The GC-MS analysis of SS-8 showed that it was composed of 16 ingredients including 9,12-octadecanoic acid (18.62%), 2,4-dihydro-5-methyl-4- (1-methylethylidene)- 2-(4-nitrophenyl)-3H- pyrazol-3-one (14.97%), hexadecanoic acid (14.23%), (z,z)-6,9-pentadecadien- 1-ol (13.73%), 5,6-dimethoxy-2-methyl benzofuran (10.95%), and 4-methoxy-2-methylcinnamic acid (5.38%). These results demonstrate that the methylene chloride extract of the stems of Z. schinifolium can induce apoptotic cell death in Jurkat T cells via intrinsic mitochondria-dependent caspase cascade regulated by Bcl-xL without involvement of the Fas/FasL system.

• IMMUNE NETWORK
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• v.21 no.3
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• pp.22.1-22.17
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• 2021

Chitinase-3-like-1 (CHI3L1) is known to induce inflammation in the progression of allergic diseases. Previous our studies revealed that 2-({3-[2-(1-cyclohexen-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanamide (K284-6111; K284), the CHI3L1 inhibiting compound, has the anti-inflammatory effect on neuroinflammation. In this study, we investigated that K284 treatment could inhibit the development of atopic dermatitis (AD). To identify the effect of K284, we used phthalic anhydride (5% PA)-induced AD animal model and in vitro reconstructed human skin model. We analyzed the expression of AD-related cytokine mediators and NF-κB signaling by Western blotting, ELISA and quantitative real-time PCR. Histological analysis showed that K284 treatment suppressed PA-induced epidermal thickening and infiltration of mast cells. K284 treatment also reduced PA-induced release of inflammatory cytokines. In addition, K284 treatment inhibited the expression of NF-κB activity in PA-treated skin tissues and TNF-α and IFN-γ-treated HaCaT cells. Protein-association network analysis indicated that CHI3L1 is associated with lactoferrin (LTF). LTF was elevated in PA-treated skin tissues and TNF-α and IFN-γ-induced HaCaT cells. However, this expression was reduced by K284 treatment. Knockdown of LTF decreased the expression of inflammatory cytokines in TNF-α and IFN-γ-induced HaCaT cells. Moreover, anti-LTF antibody treatment alleviated AD development in PA-induced AD model. Our data demonstrate that CHI3L1 targeting K284 reduces AD-like skin inflammation and K284 could be a promising therapeutic agent for AD by inhibition of LTF expression.