• Journal of the Korean Society of Food Science and Nutrition
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• v.23 no.3
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• pp.443-452
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• 1994

This study describes the effects of novel1, 25-dihydroxyvitamin D$_3$ analong[1,25(OH)$_2$-16ene-23yne-26, 27-F6-D$_3$] on proliferation of the human histiocytic lymphoma cell line U937 in vitro. We also examined the expression of c-myc oncogene in U937 cells was apparently inhibited to 62% and 87% of the control level after 4 days in the presence of 10-8M and 10-7 M of this analog, respectively. This compound morpholgically and functionally differentiated U937 cells to nonocyte-macrophage phenotype showing the increase of adherence ability to surface and a decrease of N/C ratio in Giemsa staining . Especially, nonspecific esterase activity which is a marker of cell differentiation to monocyte-macrophage was positive, and production of the positive stained cells increased in a dose dependent fashion . The expression of c-myc oncogene by 1, 25(OH)$_2$D$_3$ analog(10-7 M) was reduced by 60% at the mRNA level as determined by Northern blotting. The effects of this novel analog on cell proliferation and cell differentiation may open op new therapeutic strategies for human disorders such as psoriassis and may provide a tool to understand the mechanism of action of vitamin D$_3$ seco-steroids in malignancy.

• Journal of the Korean Chemical Society
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• v.41 no.7
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• pp.357-361
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• 1997

8-Azaxanthine (1), 3-${\beta}$-D-ribofuranosyl-8-azaxanthine (2), 3-${\beta}$-D-ribofuranosyl-8-azaxanthine-5'-monophosphate (3), and 3-${\beta}$-D-ribofuranosyl-8-azaxanthine-5'-(3-pyridinylcarbonyl)monophosphate (4) were synthesized. The in vitro antitumor activities of the synthesized compounds against P388 mouse leukemia, FM3A mammary carcinoma, and U937 human histiocytic lymphoma cells were determined by MTT assay. 2 with unnatural N-3 and C-1' glycoside bond had activity against three tumor cell lines and $IC_{50}$s of these compounds were 0.05, 0.06, and 0.06 ${\mu}mol/mL$ against three tumor cell lines, respectively. But these compounds had no antibacterial activity. $IC_{50}$s against U937 human histiocytic lymphoma cells were verified with the structural modification: $IC_{50}$s of 1, 2, 3, and 4 were 0.33, 0.06, 0.25, and 0.33 ${\mu}mol/mL$, respectively.

• Journal of the Korean Society of Food Science and Nutrition
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• v.23 no.5
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• pp.799-804
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• 1994

In order to study the antitumoral effect of Selaginella tamariscina extract, the cytotoxicities to human histiocytic lymphoma (U937) and lymphocyte were measured by MTT method. The water extract of Selaginella tamariscina showed the effective cytoxicity and increased the cytotoxicity of doxorubicine, cyclophosphamide on U937, but it has no effect on the cytotoxicity of lymphocyte. The cytotoxicity increased with the addition of other antineplastic agents but decreased with the combination of antineoplastic agent and Selaginella tamariscina in the lymphocyte. The results indicted that the side actions of retinoic acid, doxorubicine and cyclophosphamide decreased by addition of Selaginella tamariscina water extracts.

• 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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.27 no.1
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• pp.141-148
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• 1998

This study describes the effects of 1,25-dihydroxyvitamin D3[1,25(OH)2D3, calcitriol] analog, 1,25(OH)2-16ene-23yne-D3 on proliferatin and differentiatin of the human histiocytic lymphoma cell line U937. This paper also describes the effects of 1,25(OH)2-16ene-23yne-D3 on ${\gamma}$-interferon(IFN-${\gamma}$) synthesis by phytohemagglutinin-activated peripheral blood lymphocytes(PBLs). In the present investigation, 1,25(OH2)-16ene-23yne-D3 was compared to the natural metablite of vitamin D3, 1,25(OH)2D3. 1,25(OH)2-16ene-23yne-D3 was more potent than 1,25(OH)2D3 for inhibition of proliferation and induction of differentiation of U937 cells, Its effects on inhibition of proliferation was about 30-fold more potent than 1,25(OH)2D3. On induction of differentiation as measured by nonspecific esterase (NSE) activity and morphologic change, this analog morphologically and functionally differentiated U937 cells to monocyte-macrophage phenotype showing a decrease of N/C ration in Giemsa staining and the increase of adherence ability of surface. After 3 days in culture, a more significant supression of IFN-${\gamma}$ synthesis analog on supression of IFN-${\gamma}$ synthesis was a dose-dependent manner, with peak activity at 10-7M. The strong direct effects of 1,25(OH)2-16ene-23yne-D3 on cell proliferation and cell differentiation, make this compound an interesting candidate for clinical studies for several types of malignancies, and the effects on supression of IFN-${\gamma}$ synthesis provide the further evidence for a role of 1,25(OH)2-16ene-23yne-D3 in immunoregulation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.24 no.1
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• pp.1-9
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• 1995

1, 25(OH)2-23ene-D3 is a novel vitamine D3 analog which has a double bond between C-23 and C-24. We describe the effects of this analog on cell differentiation and cell proliferation in vitro using the human histiocytic lymphoma cell line U937, and on calcium metabolism in rats in vivo. In the present investigation 1, 25(OH)2-23ene-D3 was compared to the natural metabolite of vitamin D3, 1$\alpha$, 25-dihydroxycholecalciferol[1, 25(OH)2-23ene-D3 was more potent than 1, 25(OH)2-23ene-D3 for inhibition of proliferation and induction of differentiation of U937 cells. Especially, its effect on induction of differentiation, as measured by superoxide production and nonspecific esterase(NSE) activity, was about 20-fold more potent that 1, 25(OH)2-23ene-D3. This analog morphologically and functionally differentiated U937 cells to monocyte-macrophage phenotype showing a decrease of N/C ratio in Giemsa staining and the increase of adherence ability to surface. Intraperitoneal administration of 1, 25(OH)2-23ene-D3 to rats showed that the compound had at least 50 times less activity than 1, 25(OH)2-23ene-D3 in causing hypercalcemia and hypercalciuria. The strong direct effects of 1, 25(OH)2-23ene-D3 on cell proliferation and cell differentiation, coupled with its decreased activity of calcium metabolism make this compound an interesting candidate for clinical studies including patients with leukemia, as well as several skin disorders, such as psoriasis.

• Archives of Pharmacal Research
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• v.19 no.1
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• pp.62-65
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• 1996

A homologous series of twenty, hitherto unreported, analogues of 5-halosubstituted $1, 3-Bis(\omega-cyanoalkyl)uracil$acyclic nucleosides were synthesized by the series of alkylation reactions of 5-halouracils with the corresponding chloroacetonitrile, chloropropionitrile, chlorobutyronitrile and 5-chlorovaleronitrile $(Cl-(C_ 2)_n-CN: n=l, 2, 3, 4)\; in\; anhydrous\; DMSO\; (or DMF)/K_2CO_3(or NaH)\; under\; 75^{\circ}C$ temperature. Antitumor activities for the synthesized compounds were determined against three cell lines (FM-3A cell, P-388 cell and U-938 cell lines). The compounds that exhibited moderate activity to significant activity, included la-b, 2a-b, 3a-c, and 4a, whose compounds were active against P-388, FM-3A and U-937 cell lines with the compounds la, lb, and 2a, showing significant antitumor activity (inhibitory concentrations $(IC_{50})$ ranged from 2.2 to $7.0\mug/ml$). Their strucrure-activity relationship did not show any activity differences in their effective chain length (methyl, ethyl, propyl, butyl) in 1, 3-bis(.omega.-cyanoalkyl) uracils.

• Bulletin of the Korean Chemical Society
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• v.18 no.7
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• pp.711-714
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• 1997

In an effort to enhance the lipophilicities, thereby, the penetration into the cell membrane and to increase the antitumor activities of modified derivatives of 2',3'-didehydro-3'-deoxythymidine (d4T, 1), derivatives of 1 were designed and synthesized. Starting from thymidine, 1, 2',3'-didehydro-3'-deoxythymidine-5'-phosphate, disodium salt (d4T-p, 7), and two nicotinate esters of 1; 2',3'-didehydro-3'-deoxy-5'-O-(3-pyridinylcarbonyl)thymidine (d4T-NA, 5) and 2',3'-didehydro-3'-deoxy-5'-phosphoryl-O-(3-pyridinylcarbonyl)thymidine (d4T-p-NA, 8) were synthesized. The lipophilicities of the synthesized compounds were measured by P-values and antitumor activities of those were estimated against mouse leukemia P388, murine mammary carcinoma FM3A, and human histiocytic lymphoma U937 tumor cells in vitro. Although the lipophilicities of the nicotinate esters, 5 and 8 were increased 2.75- and 9.71-fold relative to that of 1 and 7, respectively, the synthesized compounds, 1, 5, 7, and 8 were found to be inactive against P388 and FM3A cells except weak antitumor activity against U937 cell.

• The Korean Journal of Mycology
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• v.27 no.4 s.91
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• pp.312-317
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• 1999

In order to study the antitumoral effect of meju extracts, which was made with a single inoculum of the microorganism, the cytotoxicity effects on several human leukemia cells such as promyelocytic leukemia cell (HL60), histiocytic lymphoma cell (U937) and acute T-cell leukemia Jurkat cell, and lymphocyte were analyzed by MTT assay. Twenty one microbes, mainly fungal genera, were isolated from Korean traditional mejus of different regions. From those collected isolates, meju was manufactured and extracted with 80% methanol, respectively. Meju methanol extracts exhibited low activites in cytotoxicity tests on HL60 cell, but high antitumoral effects of meju methanol extracts were shown on U937 and Jurkat cells. Meju methanol extracts made with a genera of Mucor, Absidia and Aspergillus showed prominant cytotoxic activities, especially. However all these extracts had no inhibitory effects on the cell growth of lymphocyte under the same conditions.

• Archives of Pharmacal Research
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• v.17 no.6
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• pp.480-482
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• 1994

A number of 5-substituted pyrimidine acyclic nucleosides were synthesized and tested for invitor cytotoxicity against four cell lines (j-82 cell, p-388 cell, FM-3A cell and U-938 cell lines). Synthesis of 1-cyanomethyl-5-substituted pyrimidines (1a-e) and 1-(4-cyanobutyl)-5-substituted pyrimidines (2a-e) was acomplished from the series of alkylation reactions ofl 5-substituted uracils with the corresponding chloacetonitrile and 5-chlorovaleronitile in DMSO under $50^{\circ}C$ temperature. These 5-substituted pyrimidine acylic nucleosides (1a-e and 2a-e) exhibited moderate to significant acitivity aginst four cell lines.