• Title/Summary/Keyword: guanidine

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Synthesis and EGFR Inhibitory Activity of 6-Guanidinoquinazoline Derivatives (6-구아니디노퀴나졸린 유도체의 합성 및 EGFR 저해 활성)

  • Yoo, Kyung-Ho;Lee, Yeo-Ran
    • Journal of the Korean Applied Science and Technology
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    • v.25 no.2
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    • pp.240-251
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    • 2008
  • The central role of tyrosine phosphorylation in cell proliferative signaling mechanisms provides another target for chemotherapy. The aim of this research is to develop new quinazoline derivatives that possess the inhibitory activity for depidermal growth factor receptor (EGFR) tyrosine kinase (TK) as protein kinase inhibitors. In this work, a series of new 4-anilino-6-guanidino-7-methoxyquinazoline derivatives (12a-l) were synthesized by the introduction of guanidine moiety at C-6 of quinazoline nucleus and evaluated for their EGFR TK inhibitory activities.

Function of hepatocyte growth factor in gastric cancer proliferation and invasion

  • Koh, Sung Ae;Lee, Kyung Hee
    • Journal of Yeungnam Medical Science
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    • v.37 no.2
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    • pp.73-78
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    • 2020
  • Cancer incidence has been increasing steadily and is the leading cause of mortality worldwide. Gastric cancer is still most common malignancy in Korea. Cancer initiation and progression are multistep processes involving various growth factors and their ligands. Among these growth factors, we have studied hepatocyte growth factor (HGF), which is associated with cell proliferation and invasion, leading to cancer and metastasis, especially in gastric cancer. We explored the intercellular communication between HGF and other surface membrane receptors in gastric cancer cell lines. Using complimentary deoxyribonucleic acid microarray technology, we found new genes associated with HGF in the stomach cancer cell lines, NUGC-3 and MKN-28, and identified their function within the HGF pathway. The HGF/N-methyl-N'-nitroso-guanidine human osteosarcoma transforming gene (c-MET) axis interacts with several molecules including E-cadherin, urokinase plasminogen activator, KiSS-1, Jun B, and lipocalin-2. This pathway may affect cell invasion and metastasis or cell apoptosis and is therefore associated with tumorigenesis and metastasis in gastric cancer.

Classification and Characterization of Exposure Rating in Humidifier Disinfectants through Calculation of PHMG Reference Concentration (PHMG (polyhexamethylene guanidine) 흡입독성참고치 산출을 통한 가습기살균제 노출등급 분류 및 특성)

  • Kim, Eunchae;Ryu, Hyeonsu;Park, Jinhyeon;Choe, Youngtae;Heo, Jung;Lee, Seula;Jo, Eun-Kyung;Choi, Yoon-Hyeong;Cho, Mansu;Yang, Wonho
    • Journal of Environmental Health Sciences
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    • v.46 no.3
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    • pp.335-343
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    • 2020
  • Objectives: The Korean Ministry of Environment has identified cases of people suspected of suffering lung disease potentially caused by polyhexamethylene guanidine (PHMG) used in humidifier disinfectants (HDs). Exposure assessment for the HDs was conducted using a questionnaire during face-to-face interview. The main purposes of this study were to develop a methodology to effectively classify levels of exposure to HDs based on a questionnaire. Methods: We first identified the overall participants' exposure characteristics by HD exposure levels; Second, we selected misclassified subjects and investigated characteristics of overestimated and underestimated subjects, focusing on exposure cases to PHMG-containing HDs. An inhalation reference concentration (RfC) for PHMG was produced on the basis of inhalation toxicity values. We made a cross-tabulation of the exposure classes (Exposure classes 1-to-4) by clinical classes based on the RfC. When the value of the exposure class minus the clinical class was 0 or 1, we assumed these were true values. When the value was ≥2 and ≤ -2, we assigned these cases to the overestimation group and underestimation group, respectively. Results: The overestimated group may have already recovered and responded excessively due to psychological anxiety or in order to receive compensation. On the other hand, relatively high mortality rates and surrogate responses for those under 10 years of age may have resulted in inaccurate exposure assessment for underestimated groups. For the characteristics of exposure, it was shown that for the underestimated group, the exposure was relatively weaker than the overestimated group, even though a high overall clinical rating was determined. Conclusions: This study may suggest ways to reduce bias and overcome the limitations of current HD exposure assessment.

Humidifier disinfectant lung injury, how do we approach the issues?

  • Choi, Jihyun Emma;Hong, Sang-Bum;Do, Kyung-Hyun;Kim, Hwa Jung;Chung, Seockhoon;Lee, Eun;Choi, Jihyun;Hong, Soo-Jong
    • Environmental Analysis Health and Toxicology
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    • v.31
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    • pp.19.1-19.7
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    • 2016
  • A large portion of the Korean population has been exposed to toxic humidifier disinfectants (HDs), and considering that the majority of the victims are infants, the magnitude of the damage is expected to be considerably larger than what has currently been revealed. The current victims are voicing problems caused by various diseases, including but not limited to lung, upper respiratory tract, cardiovascular, kidney, musculoskeletal, eye, and skin diseases, etc. However, there has been difficulty in gaining validation for these health problems and identifying causal relationships due to lack of evidence proving that toxic HD is the specific causes of extrapulmonary diseases such as allergic rhinitis. Furthermore, the victims and bereaved families of the HD case have not received any support for psychological distress such as post-traumatic stress disorder, depression, feelings of injustice, and anger caused by the trauma. In addition, because the underlying mechanisms of the toxic materials within the HDs such as polyhexamethylene guanidine phosphate, poly(oxyalkylene guanidine) hydrochloride, chloromethylisothiazolinone /methylisothiazolinone have yet to be determined, the demand for information regarding the HD issue is growing. The victims of the HD cases require support that goes beyond financial aid for medical costs and living expenses. There is a desperate need for government-led integrated support centers that provide individualized support through health screenings; in other words, we need an integrated facility that provides the appropriate social support to allow the victims to recover their physical and mental health, so as to well prepare them to return to a normal life. The implementation of such a plan requires not only the close cooperation between those departments already directly involved such as the Ministry of Environment and the Ministry of Health and Welfare, but also active support on a national scale from pan-governmental consultative bodies.

Synthesis and Characterization of Pyridinium Dinitramide Salt (피리디니움 디나이트라아마이드염의 합성과 특성연구)

  • Kim, Wooram;Kwon, Younja;Jo, Youngmin
    • Applied Chemistry for Engineering
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    • v.27 no.4
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    • pp.397-401
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    • 2016
  • A new solid oxidizer, pyridinium dinitramide (Py-DN) is a low toxic energetic material which can be utilized as a HPGP (high performance green propellant). In this work, Py-DN was synthesized using various starting materials including potassium sulfamate, pyridine hydrochloride, strong nitric acid and sulfuric acid. Physical and chemical properties of the Py-DN were characterized using UV-Vis, FT-IR and a thermal analyzer and their properties were compared to those of previously prepared salts including ammonium dinitramide[ADN, $NH_4N(NO_2)_2$] and guanidine dinitramide[GDN, $NH_2C(NH_2)NH_2N(NO_2)_2$] in our lab. Endothermic and exothermic decomposition temperatures of Py-DN were $77.4^{\circ}C$ and $144.7^{\circ}C$, respectively. The combustion caloric value was 1739 J/g, which is thermally more sensitive than that of conventional dinitramides. It may enable to lower the decomposition temperature, which can reduce preheating temperature required for satellite thruster applications.

Antimutagenic and Cytotoxic Effects of Hovenia dulcis Thumb Leaves Extracts (헛개나무 잎 추출물의 항돌연변이원성 및 암세포 성장억제효과)

  • Park, Sun-Hee;Chang, Eun-Young
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.11
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    • pp.1371-1376
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    • 2007
  • The effect of Hovenia dulcis Thumb leaves on the mutagenicity in salmonella assay and inhibitory effects on the growth of cancer cells were studied. On antimutagenicity as evaluated by Ames test, the extract and fractions of Hovenia dulcis Thumb leaves had no effect on the mutagenicity by themselves. However, methanol extract and fractions from Hovenia dulcis Thumb showed strong inhibitory effect on the mutagenesis induced by N-methyl-N#-nitro-N-nitroso-guanidine (MNNG) and benzo(a)pyrene (B(a)P). Among the solvent fractions of methanol extract, the hexane, chloroform and butanol fraction exhibited stronger inhibitory activity against MNNG and B(a)P induced mutagenesis than water fraction. For anticancer effects, Hovenia dulcis Thumb loaves extract and fractions against cancer cell lines including HepG2 and HT29 were investigated. The methanol extract, the hexane fraction and the chloroform fraction of Hovenia dulcis Thumb leaves inhibited growth of cancer cells but they had no effect on the cytotoxicity of normal human liver cells under the same conditions.

Estimation of Humidifier Disinfectant Amounts Inhaled into the Respiratory System (가습기 살균제 피해자 호흡기로 흡입된 가습기 살균제 양 추정 - 호흡기 외부(external) 및 내부 노출(internal exposure) 추정 방법과 사례 -)

  • Park, Dong-Uk;Ryu, Seung-Hun;Lim, Heung-Kyu;Kim, Sun-Kyung;Roh, Hyun-Suk;Cha, Won-Seok;Park, Dooyong
    • Journal of Environmental Health Sciences
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    • v.42 no.3
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    • pp.141-146
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    • 2016
  • In South Korea, many cases of humidifier disinfectant-associated lung injury (HDLI) have been reported among people who used humidifier products containing humidifier disinfectant (HD). The objectives of this study are to estimate both airborne HD concentration in the room where HD was used and the amount of humidifier disinfectant absorbed into the respiratory system. Information and data on the HDs were collected using a structured questionnaire and home environmental investigations include the volume of HD (ml) and hours used per day, concentration of disinfectants contained in the HD brand (${\mu}g/ml$), volume of the room ($m^3$), assumed ventilation rate ($m^3/hr$) and breathing rate assumed ($m^3/hr$). We used children aged under five years old as a sample and estimated both airborne HD concentrations and amount of HD absorbed into the respiratory system. The estimated airborne concentration of HD in the room ranged from 68 to $369{\mu}g/m^3$ for PHMG (polyhexamethylene guanidine phosphate) and from 16 to $239{\mu}g/m^3$ for PGH (oligo (2-(2-ethoxy) ethoxyethyl guanidine). The amount of HD absorbed in the respiratory system per day was estimated to range from 227 to $1,225{\mu}g$ for PHMG and from 53 to $794{\mu}g$ for PGH. In conclusion, a great amount of HD was likely absorbed into respiratory system, likely beyond the level of the capacity of the immune system to remove the HD absorbed.

Electrospray ionization tandem mass fragmentation pattern of camostat and its degradation product, 4-(4-guanidinobenzoyloxy)phenylacetic acid (Camostat 및 분해산물 4-(4-guanidinobenzoyloxy)phenylacetic acid의 전자분무 이온화 텐덤 질량 fragmentation 패턴)

  • Kwon, Soon-Ho;Shin, Hye-Jin;Park, Ji-Myeong;Lee, Kyoung-Ryul;Kim, Young-Jin;Lee, Sang-Hoo
    • Analytical Science and Technology
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    • v.24 no.2
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    • pp.78-84
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    • 2011
  • The fragmentation patterns of a serine protease inhibitor, camostat, and its degradation product, 4-(4-guanidinobenzoyloxy)phenylacetic acid (GBPA), were for the first time investigated by a triple quadrupole tandem mass spectrometry equipped with an electrospray source (ESI-MS/MS) in positive and/or negative ion mode under collision-induced dissociation (CID). The positive CID spectrum of camostat showed distinctly that the single bond (C-O) cleavage between carbonyl group and oxygen atom of the ester bonds of the compound favorably occurred and then the loss of N,N-dimethylcarbamoylmethyl group was more susceptible than that of guanidine moiety. In the positive ion CID spectrum of GBPA, the initial cleavage between the carbonyl group and oxygen atom of 4-guanidinobenzoyloxy group also occurred, yielding the most abundant fragment ion at m/z 145. On the other hand, the negative CID spectrum of GBPA characteristically showed the occurrence of the most abundant peak at m/z 226 resulting from the sequential neutral losses of $CO_2$ and HN=C=NH from the parent ion at m/z 312.

Comparison of Biochemical Characterization of Korean and Chinese Mung Bean Lectin (한국산 녹두와 중국산 녹두에 있어서 Lectin의 생화학적 특성 비교)

  • Roh, Kwang Soo
    • Journal of Life Science
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    • v.24 no.6
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    • pp.603-611
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    • 2014
  • The lectins were separated from Korean and Chinese mung bean seeds finally via chromatography using Sephadex G-100 and their biochemical features were studied and compared. They showed no hemagglutination with human red blood cells regardless of trypsin treatment and showed hemagglutination with only trypsin treated rabbit red blood cells. The molecular weights of two lectins were identified as 54 kDa and 28 kDa by SDS-PAGE. It was found that while the optimal reaction temperature of the lectin from Korean mung bean was $60^{\circ}C$, that of the lectin from Chinese mung bean seeds was $50^{\circ}C$. It was found also that the most thermal stable temperature of the seed lectin from Korean mung bean seeds was $50^{\circ}C$ and the lectin from Chinese mung bean was $40-50^{\circ}C$. The lectin from Korean mung bean seeds showed the highest activity at pH 3.2 and the lectin from Chinese mung bean showed the highest activity at pH 6.2. It was identified that when treating a denaturant, thiourea and guanidine-HCl resulted in no hemagglutination, so they induced denaturalization. It was identified also that there was no hemagglutination with urea, so it did not induced denaturalization. They showed no septicity to 6 types of carbohydrates including D-glucose. In addition, the lectins from the two mung bean seed had specificity to metal ions.

Distribution of Health Problems Associated with Humidifier Disinfectant by Year (연도별 가습기 살균제 피해자 분포 고찰 - 폐 손상 중심 -)

  • Park, Dong-Uk;Ryu, Seung-Hun;Roh, Hyun-Suk
    • Journal of Environmental Health Sciences
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    • v.42 no.6
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    • pp.365-374
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    • 2016
  • Objectives: Studies are needed to examine the characteristics of health effects reported by people who used humidifier disinfectant (HD), including the distribution of victims. Methods: We analyzed the distribution of health effects including lung injury that were asserted by a total of 699 individuals who registered with the first through third national programs to determine health effects associated with the use of HD. Results: We found that HD-associated lung injury (HDLI) occurred every year from 2002 through 2011, and in 2011 for 37.2% (n=96) of the total of 258 clinically evaluated HDLI victims. More than half of the victims responded that they were victimized between 2010 and 2011. This was consistent among all classifications by sex, age, HD brand and HD chemical ingredient. Conclusion: This study assumed that the major reason for the outbreak of the health effect between 2010 and 2011 could be the variations in concentrations and physical properties related to polyhexamethylene guanidine (PHMG). Further studies are necessary to examine if some factors related to the chemical disinfectants contained in HD brands may have caused the massive outbreak of health effects including HDLI.