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C K Ryu

Publications and source records attributed to C K Ryu.

27 records · Page 2Linked to original sources
PubMed1999

Stability, blood partition, and protein binding of NQ12, a new naphthoquinone derivative.

The stability of a new phospholipase A2 inhibitor, NQ12, in various pH solutions, human plasma, urine, and gastric juices, and rat liver homogenate, the blood partition of NQ12 between plasma and blood cells of rat blood, and the factors influencing the binding of NQ12 to 4% human serum albumin (HSA) using an equilibrium dialysis technique were evaluated. NQ12 was unstable in various pH solutions, human plasma and urine, and rat liver homogenate when incubated in a water-bath shaker kept at 37 degrees C and at a rate of 50 oscillations per min. However, NQ12 was stable for up to 3-hr incubation in human gastric juice. The plasma-to-blood cell concentration ratios of NQ12 were independent of NQ12 rat blood concentrations when the whole blood was incubated for up to 2-hr; the mean (+/- standard deviation) values were 0.112 +/- 0.0650 and 0.172 +/- 0.105 at initial blood NQ12 concentrations of 10 and 20 microg/ml, respectively. The binding of NQ12 to 4% HSA was considerable (higher than 99%) at NQ12 concentrations ranging from 10 to 100 microg/ml in 4% HSA. The unbound fraction of NQ12 was dependent on NQ12 concentrations, pHs of buffer, and HSA concentrations, but was independent of the concentrations of sulfisoxazole or salicylic acid, incubation temperature, buffers containing various concentrations of chloride ion, and concentrations of heparin and alpha-1-acid glycoprotein.

Animals↗
PubMed1998

Partial purification of protein farnesyl cysteine carboxyl methyltransferase from bovine brain.

C-terminal farnesyl cysteine carboxyl methylation has been known to be the last step in the post-translational modification processes of several important signal transduction proteins in eukaryotes including ras related GTP binding proteins and the gamma-subunit of heterotrimeric G proteins. Protein farnesyl cysteine carboxyl methyltransferase (PFCCMT; EC, 2.1.1.100) catalyzing the reaction is well characterized as being stimulated by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and suppressed by N-acetyl-S-farnesyl-L-cysteine (AFC). As an initial step to understand the physiological significance of the process, we attempted to purify the enzyme, which was partially purified 130-fold (specific activity, 143 pmol of methyl group transferred/min/mg of protein) with yield of 1.8% after purification by fast protein liquid chromatography (FPLC) on a Superdex 75 column. The enzyme was further purified with non denaturing polyacrylamide gel electrophoresis (ND-PAGE) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The molecular weight of PFCCMT was determined to be about 30 kDa based on Superdex 75 FPLC as well as photoaffinity labelling with S-adenosyl-L-[methyl-3H] methionine ([methyl-3H]SAM). The partially purified enzyme (Superdex 75 eluate) was found to be characteristically affected by GTP gamma S, being activated about 40-fold in 2 mM, in contrast to ATP which did not show any effect on enzyme activity. Meanwhile, the enzyme was found to be markedly inhibited by AFC, reaching 0 activity in 2 mM. These observations strongly suggested that the partially purified enzyme was PFCCMT.

Acetylcysteine↗
PubMed1998

Synthesis and antifungal evaluation of 6-(N-arylamino)-7-methylthio-5,8-quinolinediones.

A series of 6-(N-arylamino)-7-methylthio-5,8-quinolinedione derivatives 4a-4l was newly synthesized for the evaluation of antifungal activity. 6-(N-Arylamino)-7-methylthio-5,8-quinolinediones were prepared by regioselective nucleophilic substitution of 6,7-dichloro-5,8-quinolinediones with arylamines in the presence of Ce3+, and Na2S/dimethylsulfate. The MIC values of 4a-4l were determined for antifungal susceptibility in vitro against Candida species by agar streak method. The derivatives 4a-4l had generally potent antifungal activities against all human pathogenic fungi. Especially they had the most potent activity against C. krusei at 12.5-0.8 micrograms/ml. Compounds 4d, 4g, 4h, 4j and 4k had more potent antifungal activities than fluconazole. Compounds 4g and 4h completely inhibited the fungal growth at 0.8-6.3 micrograms/ml against all Candida species, while fluconazole inhibited the growth at 25 micrograms/ml. The compounds such as 4g and 4h containing an N-(4-bromo-2-methylphenyl)- or N-(4-bromo-3-methylphenyl)amino substituent exhibited the most potent antifungal activities.

Aminoquinolines↗
PubMed1997

Thromboxane A2 synthase inhibition and thromboxane A2 receptor blockade by 2-[(4-cyanophenyl)amino]-3-chloro-1,4-naphthalenedione (NQ-Y15) in rat platelets.

The effects of 2-[(4-acetylphenyl)amino]-3-chloro-1,4-naphthalenedione (NQ-Y15), a synthetic 1,4-naphthoquinone derivative, on platelet activity and its mechanism of action were investigated. NQ-Y15 caused a concentration-dependent inhibition of the aggregation induced by thrombin, collagen, arachidonic acid (AA), and A23187. The IC50 values of NQ-Y15 on thrombin (0.1 U/mL)-, collagen (10 microg/mL)-, AA (50 microM)-, and A23187 (2 microM)-induced aggregation were 36.2 +/- 1.5, 6.7 +/- 0.7, 35.4 +/- 1.7, and 93.1 +/- 1.4 microM, respectively. NQ-Y15 also inhibited thrombin-, collagen-, AA-, and A23187-stimulated serotonin secretion in a concentration-dependent manner. However, a high concentration (100 microM) of NQ-Y15 showed no significant inhibitory effect on ADP-induced primary aggregation, which is independent of thromboxane A2 (TXA2) production in rat platelets. In fura-2-loaded platelets, the elevation of intracellular free calcium concentration stimulated by AA, thrombin, and 4-bromo-A23187 was inhibited by NQ-Y15 in a concentration-dependent manner. The formation of TXA2 caused by AA, thrombin, and collagen was inhibited significantly by NQ-Y15. NQ-Y15 inhibited TXA2 synthase in intact rat platelets, since this agent reduced the conversion of prostaglandin (PG) H2 to TXA2. Similarly, NQ-Y15 selectively inhibited the TXA2 synthase activity in human platelet microsomes, whereas it had no effect on activity of phospholipase A2, cyclooxygenase, and PGI2 synthase in vitro. NQ-Y15 inhibited platelet aggregation induced by the endoperoxide analogue U46619 in human platelets, indicating TXA2 receptor antagonism, possibly of a competitive nature. These results suggest that the antiplatelet effect of NQ-Y15 is due to a combination of TXA2 synthase inhibition with TXA2 receptor blockade, and that it may be useful as an antithrombotic agent.

Animals↗
PubMed1994

The antifungal activities of some 6-[N-(halophenyl)amino]-7-chloro-5,8-quinolinediones against Candida species.

A series of 6-[N-(halophenyl)amino]-7-chloro-5,8-quinolinedione derivatives 1-10 were tested for antifungal susceptibilities, in vitro, against pathogenic Candida species such as C. albicans, C. glabrata, C. krusei, C. parapsilosis and C. tropicalis. The MICs were determined by the standard macrodilution techniques, according to the NCCLS 1992 guidelines. The 6-[N-(halophenyl)amino]-7-chloro-5,8-quinolinedione derivatives showed generally potent antifungal activities against pathogenic Candida species. Among them, derivative 1, 2, 5 and 7 showed more potent antifungal activities than ketoconazole. All derivatives 1-10 had specially potent activities against C. tropicalis. Derivative 1 and 2 containing (N-3,4-dihalo-phenyl)amino moiety exhibited the potent antifungal activities. Derivative 2 with (3,4-dichlorophenyl)amino substituent was the most effective in preventing the growth of Candida species at MICs 4 micrograms/ml respectively.

Antifungal Agents↗
PubMed1972

Littre's hernia.

Explore the source record for details and available documents.

Diverticulum↗
PubMedDate not supplied

Effect of glutathione depletion on haemoglobin and membrane integrity of red blood cells of rats.

The effects of streptozocin (streptozotocin) and water-soluble menadione (menadione bisulphite, sodium salt) on the haemoglobin content and membrane integrity of red blood cells were investigated. Both menadione bisulphite and streptozocin significantly depleted glutathione but menadione bisulphite was much more effective in reducing glutathione than was streptozocin. Menadione bisulphite, at concentrations above 0.1 mM, caused substantial conversion of oxygenated haemoglobin into methaemoglobin while streptozocin did not alter the haemoglobin content of the red blood cells at concentrations of up to 100 mM. Both agents demonstrated only a modest ability to haemolyse the red blood cells, even at concentrations up to 300 mM. These results suggest that depletion of glutathione by menadione causes the conversion of oxyhaemoglobin to methaemoglobin. In contrast, streptozocin-induced glutathione depletion does not seem to be well correlated with alterations in haemoglobin content.

Animals↗
PubMedDate not supplied

Pharmacokinetics, stability, and blood partition of 7-anilino-5,8-isoquinolinedione, a new isoquinonlinedione derivative.

Pharmacokinetics of IQO4, a new isoquinolinedione derivative, after 30-min intravenous administration of the drug, 5 mg/kg, to rats, the stability, and the blood partition between plasma and blood cells of IQO4 were evaluated. After intravenous administration, IQO4 was eliminated fast with the mean total body clearance of 105 ml/min/kg. IQO4 was almost completely metabolized in rats; 5.18% of intravenous dose of IQO4 was excreted in 24-hr urine and IQO4 was under detection limit in whole gastrointestinal tract as 24 hr. IQO4 has a good affinity to liver, small intestine, heart, lung, and kidney as reflected to greater-than-unity tissue-to-plasma ratios. IQO4 was unstable in rat whole blood, plasma, and liver homogenates when incubated in a water-bath shaker for 24 hr kept at 37 degrees C and at a rate of 50 oscillations per min. The disappearance rate constants of IQO4 were 0.0611, 0.O436, and 0.174 hr(-1) for rat whole blood, plasma, and liver homogenates, respectively. However, IQO4 was stable for up to 3-hr incubation in human gastric juices. The plasma-to-blood cell concentration ratios of IQO4 were independent of initial blood concentrations of IQO4, 0.5, 2, and 10 microg/ml, when the rabbit whole blood was incubated for up to 120 min; the ratios were in the range of 1.56-3.60. Since IQO4 was unstable in blood, considerable in vitro 'blood storage effect' in the plasma concentration of IQO4 was observed.

Animals↗