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Synthesis and Structure-Activity Relationship Studies of 2,3-Dihydroimidazo[2,1-a]isoquinoline Analogs as Antitumor Agents

  • Cheon, Seung-Hoon;Park, Joon-Suck;Jeong, Seon-Hee;Chung, Byung-Ho;Choi, Bo-Gil;Cho, Won-Jae;Kang, Boo-Hyon;Lee, Chong-Ock
    • Archives of Pharmacal Research
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    • v.20 no.2
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    • pp.138-143
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    • 1997
  • 5-Aryl-2,3-dihydroimidazo[2,1-a]isoquinolines were reported to have strong antitumor activity and one of the derivatives such as $5-[4^{l}$ -(piperidinomethyl)phenyl]-2,3-dihydroimidazo[2,1-a] isoquinoline (1, SDZ 62-434) was found to be more effective than the clinical cytostatic agent edelfosine (2) in in vitro and in vivo assays. Currently SDZ 62-434 is in clinical trials in Europe. The structure-activity relationship studies of SDZ 62-434 showed that compounds with substitution on ring A were less active than the lead compound. Ring B in SDZ 62-434 was essential for the activity because compounds without B ring had no antitumor activity. Among the 3-arylisoquinolin-1-one derivatives, $3-[4^{I}$-(piperidinomethyl)phenyl] substituted analog had no antitumor activity but simple phenyl substituted compound, such as 4, showed the most potent antitumor activity in various human tumor cell lines.

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Effects of Lower Rib Expansion Limitation on Maximal Respiratory Pressure and Abdominal Muscle Activity During Maximal Breathing in Healthy Subjects

  • Lee, Gyu-wan;Yoon, Tae-Lim;Lee, Young-jung;Kim, Ki-song;Yi, Chung-hwi
    • The Journal of Korean Physical Therapy
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    • v.32 no.6
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    • pp.394-399
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    • 2020
  • Purpose: The aim of this study was to determine the effects of lower rib cage lateral expansion limitation on the maximal inspiratory and expiratory pressures and on abdominal muscle activity during maximal respiratory breathing in healthy subjects. Methods: Fifteen healthy male subjects voluntarily participated in this cross-sectional study. During maximal breathing, maximal inspiratory and expiratory pressures were measured, and abdominal muscle activity was determined with using surface electromyography. Also, the measurement was repeated with using a non-elastic belt to the lower rib cage for limiting of lateral expansion. A Wilcoxon signed-rank test was performed for obtaining the statistical difference with a significance level of 0.05. Results: The findings of this study are as follows: 1) There were no significant differences in maximal inspiratory and expiratory pressure with and without lower rib cage lateral expansion (p>0.05), 2) There was no significant difference in abdominal muscle activity during the maximal inspiratory phase (p>0.05). However, right external oblique muscle activity decreased significantly during maximum exhalation with lower rib expansion limitation (p<0.05). Conclusion: The results of the current study indicate that a non-elastic belt was effective in decreasing right external oblique muscle activity during forced expiratory breathing in healthy subjects.

Free radical Scavenging Activities and Inhibitory Effects on Xanthine oxidase of Buckwheat (Suwon No. 5) (수원 5호 메밀의 유리라디칼 소거 및 Xanthine oxidase 활성 저해)

  • 서형주;정수현;김영순;이성동
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.26 no.3
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    • pp.411-416
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    • 1997
  • To examine the free radical scavenging activities from buckwheat, Suwon No. 5 was extracted with various solvents. The seed of Suwon No. 5 had a high contents of carbohydrate, but the vegetable of that had a 31.4% of protein, 28.6% of ash and 25.7% carbohydrate as moisture free basis. Phenols contents of vegetable extracts had higher than those of seed extracts. Acetone extract of vegetable showed the greatest electron donating ability. Butanol and acetone extracts of vegetable showed high inhibitory effect on lipid peroxidation. Acetone extract of vegetable has also excellent activity in the superoxide radical scavenging activity by xanthine/xanthine oxidase-cytochrome c reduction system. The inhibitory effects of extracts on xanthine oxidase were measured. Acetone extract had the strongest inhibitory effect on xanthine oxidase and $IC_{50}$ was 2.2$\mu\textrm{g}$.

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Antimicrobial Effect of Monascus Strains Isolated from Ang-Khak (홍국으로부터 불리한 Monascus 균주의 향균효과)

  • 류춘선;김영배;황한준
    • Journal of Food Hygiene and Safety
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    • v.10 no.4
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    • pp.271-277
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    • 1995
  • Total 29 Monascus strains were isolated from Ang-Khak and 4 of them were selecte based on the relative intensity of soluble red pigment and growth rate. The optimum growth temperature of the selected isolates was 32.5$^{\circ}C$ on malt extract agar(MEZ) plate. The optimum growth pH was 5.0 on czapek yeast extract agar plate, while it was pH 6.2 or 6.5 on MEA plate. Isolate No. 116, especially, showed the strongest animicrobial activity aganist Bacillus subtilis and Staphylococcus aureus but much less aganist Escherichia coli and Enterobacter aerogenes. The maximun antimicrobial activity of isolate No. 116 against St. aureus was achieved at initial pH 5.3 on rice extract broth. The acitivity was increased with increasing amount of culture broth concentrate of isolate No. 116.

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Synthesis and Nrf2 Activating Ability of Thiourea and Vinyl Sulfoxide Derivatives

  • Shim, Young Sun;Hwang, Hyun Sook;Nam, Ghilsoo;Choi, Kyung Il
    • Bulletin of the Korean Chemical Society
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    • v.34 no.8
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    • pp.2317-2320
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    • 2013
  • Thiourea and vinyl sulfoxide derivatives were designed based on the structures of sulforaphane and gallic acid, prepared and tested for HO-1 inducing activity as a measure of Nrf2 activation, and inhibitory effect on NO production as a measure of anti-inflammatory activity. Both series of compounds showed moderate activity on HO-1 induction, and no inhibitory effect on NO production. Interestingly the thiourea compound 6d showed better HO-1 induction (71% SFN) than the corresponding isothiocyanate compound 6a (55% SFN). Overall, it seemed that more efficient electrophile is needed to get more effective Nrf2 activator.

Antioxidation and Functional Cosmetics Activity of Humulus japonicus Sieboid & Zucc. According to Collection Time and Extraction Solvent (채취 시기 및 추출 용매에 따른 환삼덩굴의 항산화 및 기능성 화장품 활성)

  • Chae, Jungwoo;Jo, Huiseon;Yeom, Hyeonji;Lee, Jin-young
    • Journal of Korean Society of Forest Science
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    • v.110 no.2
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    • pp.254-265
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    • 2021
  • As a result of measuring the polyphenol content of Humulus japonicus (HJ) extract according to the collection time and extraction solvent, bothhot water extract and 70% ethanol extract were collected and extracted in June, and the polyphenol content was high. When the harvesting time was the same, the polyphenol content of the ethanol extract was higher than that of the hot water extract. As a result of measuring the antioxidant activity of HJ extract by measuring electron-donating ability, SOD-like activity, and ABTS radical scavenging ability, HJ6E, which has the highest polyphenol content, showed the highest activity. In addition, in the case of the extract collected in August, the polyphenol content was similar. However, the antioxidant activity of the ethanol extract was high, sothe antioxidant activity remained high when extracted with 70% ethanol. As a result of measuring tyrosinase inhibitory activity for evaluating skin whitening activity, HJ6W did not show any activity. The activity at the highest concentration was 16.18% for HJ8W, 8.07% for HJ6E, and 14.7% for HJ8E. Therefore, the content of ingredients showing skin whitening activity was higher in August than in June. In the elastase inhibitory activity for evaluating the anti-wrinkle activityof the skin, the ethanol extract showed very little activity, and the hot water extract did not. In addition, since all extracts do not show astringent activity, it is judged that it is not appropriate to use HJ as a functional ingredient for preventing wrinkle formation. As a result of measuring the cell viability of HJ6E, which showed the highest polyphenol content and antioxidant activity, it showed a cell proliferation effect at low concentrationsbut strong cytotoxicity at concentrations above 50 ㎍/mL. In the case of the NO production inhibitory ability, as the concentration increased, the NO production of Raw 264.7 was suppressed. Theamount of NO production at 1,000 ㎍/mL decreased to 40.7%. However, whether these results are due to cytotoxicity or the extract's efficacy is a part that requires further research.

Effect of Rapid Rotating Shift Work on the Urinary $Na^+,K^+,Cl^-$ (빠른 교대근무가 요중 $Na^+,K^+,Cl^-$의 배설에 미치는 영향)

  • Min, Soon;Moon, Dae-Soo;Im, Wook-Bin
    • Journal of Korean Academy of Nursing
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    • v.28 no.4
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    • pp.869-880
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    • 1998
  • In order to investigate of the effects of rapid rotating shift work on physiological stress, the activities of urinary Na$^{+}$, $K^{+}$, Cl$^{[-10]}$ were measured in 14 rotational shift nurses, during day shifts(8AM-4PM, n=4), evening shifts(4PM-l2MN, n=5), and night shifts(12MN-8AM, n=5) in hospital twenty students attending nursing college a used as a control group. Urine specimens were collected in 30 minutes before and after work on the second day of shift work. In day shift nurses, Na$^{+}$ activity was 137mM at 8AM and increased to 206mM at 4PM, whereas $K^{+}$ activity was 42mM at 8AM and no significant change at 4PM. Cl$^{[-10]}$ activity was changed from 234mM to 344mM at 4PM at 8AM. In the evening shift, Na$^{+}$ activity was 117mM at 4PM and 140mM at 12MN, $K^{+}$ activity was 22mM and 32mM, respectively. Cl$^{[-10]}$ activity was 169mM and changed to 270mM. During the night shift, Na$^{+}$ activity was 128mM at 12MN and changed to 161mM at 8AM, $K^{+}$ activity was 42mM at 12MN and 8AM, and Cl$^{[-10]}$ activity was from 303mM and changed to 355mM. In general, the urinary ion activities seemed to increase after work, however there were no significant changes in ion activities except the Na$^{+}$ increase in day shift. The mean of the activities of $K^{+}$ and Cl$^{[-10]}$ before and after work during the day and night shift were significantly higher than those in control group (P<0.05). $K^{+}$ activities were also higher than that of evening shift(P<0.05). However, there was no difference in Na$^{+}$ activity among the control group and three shifts. There was a significant relationship among urinary Na$^{+}$, Cl$^{[-10]}$ and $K^{+}$ in the control group and rotating shift nurses except between Na$^{+}$ and $K^{+}$ in shift. The relationship between Na$^{+}$ and Cl$^{[-10]}$ was low in shift work and there was no significant relationship between Na$^{+}$ and $K^{+}$ in shift, suggesting that the active regulation $K^{+}$ and/or Na$^{+}$ in response to stress upon the shift work disruped the ratio of urinary Na$^{+}$ to $K^{+}$ and also lowered the relationship between $K^{+}$ and Cl$^{[-10]}$ . These results suggest that nurses working the day shift were overloaded and under stress, and the night shift interfered with the physiological rhythm of the nurses.red with the physiological rhythm of the nurses.

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Physiological Activities of Extract from Edible Mushrooms (주요 식용버섯 추출물의 생리활성 효과)

  • Choi, Se-Jin;Lee, Yeon-Sil;Kim, Jin-Kyung;Kim, Jin-Kyu;Lim, Soon-Sung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.8
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    • pp.1087-1096
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    • 2010
  • This study was conducted to investigate the physiological activity of extracts of fresh mushrooms. The components were extracted by hot water; subsequently, the hot-water extract was subjected to 60% ethanol precipitation to yield high-molecular-weight (HMW) and low-molecular-weight (LMW) fractions. Total polyphenol contents, $\beta$-glucan contents, electron-donating ability (EDA), superoxide dismutase (SOD)-like activity, nitrite-scavenging activity, fibrinolytic activity, nitric oxide (NO) production, and inhibition of NO production of the mushroom extracts were measured using lipopolysaccharide (LPS)-stimulated murine macrophages, RAW 264.7 cells. The extracts of Lentinus edodes (Berk.) Singer and Pleurotus ostreatus (Fr.) Kummer contained the highest levels of $\beta$-glucan (33.5% and 25.57%, respectively). Further, the LMW fractions of the Phellinus linteus contained the highest levels of polyphenols (233.23 mg/g). The EDA of LMW fractions (10 mg/mL) of the Phellinus linteus and Agaricus bisporus were 80.74% and 51.35%, respectively. Further, SOD-like activities of the LMW fractions were high as compared to those of the HMW fractions. Nitrite-scavenging activities of the LMW fractions (pH 1.2; concentration, 10 mg/mL) of the Phellinus linteus and Pleurotus ostreatus (Fr.) Kummer were 75.95% and 41.05%, respectively. The fibrinolytic activity of the LMW fractions of all mushrooms showed no enzyme activity by fibrin plate assay. The fibrinolytic activity of the extracts of Tricholoma matsutake was the greatest inhibitory activity at 60.4%. Further study revealed that the mushroom extracts exhibited anti-inflammatory effects on RAW 264.7 cells. The LMW fraction ($500\;{\mu}g/mL$) of the Phellinus linteus considerably inhibited NO production (100%).

Anti-Inflammatory Activity of the Total Flavonoid Fraction from Broussonetia papyrifera in Combination with Lonicera japonica

  • Jin, Jeong-Ho;Lim, Hyun;Kwon, Soon-Youl;Son, Kun-Ho;Kim, Hyun-Pyo
    • Biomolecules & Therapeutics
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    • v.18 no.2
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    • pp.197-204
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    • 2010
  • To establish the anti-inflammatory activity of the total flavonoid fraction of the root barks of Broussonetia papyrifera (EBP) and a new formula, the ethanol extract of the root barks of B. papyrifera was fractionated with ethylacetate, yielding the hydrophobic prenylated flavonoid-enriched fraction. EBP and the ethanol extract of the whole Lonicera japonica (ELJ) plant were then mixed at a ratio of 1:1 (w/w) to give a new preparation (BL) in the hope of obtaining an optimal formula with a higher anti-inflammatory activity. Evaluation of the effects of these preparations on A23187-treated rat basophilic leukemia (RBL-1) cells revealed that EBP potently inhibited 5-lipoxygenase (5-LOX), while ELJ showed weak inhibition. Additionally, the mixture (BL) clearly showed stronger inhibitory effects against 5-LOX than either preparation alone. These preparations also inhibited cyclooxygenase-2-catalyzed $PGE_2$ and inducible nitric oxide (NO) synthase-catalyzed NO production by lipopolysaccharide-treated RAW 264.7 cells. When tested against arachidonic acid-induced mouse ear edema, EBP showed strong inhibitory activity at doses of 5-200 mg/kg when administered orally, but BL had obviously stronger inhibitory effects. When tested against ${\lambda}$-carrageenan-induced paw edema in mice, BL showed a potent and synergistic anti-inflammatory effect. In addition, in the acetic acid-induced writhing test, BL was found to have strong analgesic activity at 50-400 mg/kg. Taken together, these results indicate that each of these preparations exert anti-inflammatory activity in vitro and in vivo. In particular, BL showed stronger anti-inflammatory activity than EBP, and these anti-inflammatory effects were partially related to the inhibition of eicosanoid and NO production. BL may be useful for the treatment of human inflammatory disorders.

The comparative study on physiological activity of White ginseng, Red ginseng and Black ginseng extract (백삼, 홍삼, 흑삼 추출물의 생리활성 비교 연구)

  • Jang, A-Young;Sueng, Yun-Chul;Ji, Joong-gu
    • Journal of Digital Convergence
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    • v.14 no.5
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    • pp.459-471
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    • 2016
  • This study presents a comparative study for differences in efficacy and ingredient of white ginseng(WG), red ginseng(RG), and black ginseng(BG) using anti-oxidative activity test and anti-inflammatory activity test. In the results of cytotoxicity test for WG, RG, and BG, the survival rate of all cells was more than 95%. In the total polyphenol analysis, DPPH, ABTS radical scavenging test, and ROS production test, BG showed higher anti-oxidant activity than WG and RG. RG and WG showed higher inhibition activity of NO production and $PGE_2$ production, respectively. As results of the test for the effect on reduction of inflammatory cytokine production, WG and RG were effective on reduction of IL-$1{\beta}$ production, and BG was effective on reduction of IL-6. In the case of TNF-${\alpha}$ production, there was no difference among samples. This study could be useful basic data for the development of functional food and the fabrication of safe cosmetic.