• 한국식품영양과학회지
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• 제23권3호
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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.

• 대한화학회지
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• 제41권7호
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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) 그리고 3-${\beta}$-D-ribofuranosyl-8-azaxanthine-5'-(3-pyridinylcarbonyl)monophosphate(4)를 합성한 후 Mouse leukemia P388, Murine mammary carcinoma FM3A, Human histiocytic lymphoma U937 암세포들에 대해 시험관내 항암활성을 MTT를 이용한 방법으로 예측하고 $IC_{50}$(${\mu}mol/mL$)으로 나타내었다. 그 결과, 비정상적인 염기의 N-3와 당의 C-1' glycoside 결합을 가진 2는 세가지의 암세포에 대해 감수성이 좋아 $IC_{50}$이 각각 0.05, 0.06, 0.06 ${\mu}mol/mL$이었으나 항세균 활성 예측에서는 감수성을 보이지 않았다. Human histiocytic lymphoma U937 세포에 대한 $IC_{50}$은 1이 0.33, 2는 0.66, 3은 0.25 그리고 4는 0.33 ${\mu}mol/mL$로 구조 변화에 따라 서로 다른 값을 보였다

• 한국식품영양과학회지
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• 제23권5호
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• pp.799-804
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• 1994

천연물에서 직접적인 암세포 살해능을 가지며, 동시에 중증의 백혈구 감소증을 억제시킬 수 있는 물질을 탐색하기 위하여 암세포주인 U937 human lymphoma cell과 정상면역 세포인 lymphocyte에 대한 권백 수침 엑기스의 암세포 살해능과, 현재 임상에서 응용되고 있는 화학요법제인 retinoic acid, doxorubicine, cyclopho-sphamide와의 병용요법이 암세포(U937)와 정상세포(lymphocyte)에 미치는 영향을 MTT 분석법을 이용하여 비교 관찰하여 다음과 같은 결과를 얻었다. 권백 수침 엑기스 단독첨가시 권백 수침 엑기스는 암세포인 U937 human iymphoma cell의 성장을 유의적으로 억제시켰으며, 정상면역세포인 lymphocyte에는 영향을 미치지 않았따. 권백 수침 엑기스와 호학요법제를 병용 첨가시 화학요법제를 단독 처리했을 때 보다 권백 수침 엑기스(1mg/ml)와 화학요법제를 병용하였을 때, U937의 세포살해능의 현저히 증가되었고, 한편 lymphocyte의 세포살해능은 감소하였다. 이상의 결과에서 화학요법제와 권백을 병용 투여함으로서 암세포 살해능은 증가되고, 정상세포 살해능은 감소되었으므로 화학요법제의 가장 큰 부작용인 immunosupression 중 $leucopeenia^{20~30}$를 감소시킬 수를 감소시킬 수 있을 것으로 사료된다.

• 생명과학회지
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• 제9권1호
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• pp.58-62
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• 1999

몇가지 nucleoside 5'-monophosphate 유도체들과 지질 친화성을 증가시킨 nucleoside 5'-(3-pyridinyl carbonyl)monophosphate 유도체들을 합성한 후 Mouse leukemia P388, Murine mammary carcinoma FM3A, Human histiocytic lymphoma U937 세포들에 대해 시험관내에서 항암활성을 MTT를 이용한 방법으로 나타내었다. 그 결과 uridine 5'-(3-pyridinylcarbonyl) monophosphate(7)와 2',3'-didehydro-3'-deoxythymidine-5' -(3-pyridinylcarbonyl) monophoshate(8)의 inhibition이 uridine 5'-monophosphate(1)와 2',3'-didehydro-3'-deoxythymidine-5'-monophosphate(4) 보다 각각 증가하였다. 이는 nucleoside 5'-(3-pyridinylcarbonyl) monophosphate 유도체들이 임상적 한계를 극복할 수 있는 가능성을 보인 것이다.

• 한국식품영양과학회지
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• 제27권1호
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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.

• 한국식품영양과학회지
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• 제24권1호
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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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• 제19권1호
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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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• 제18권7호
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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.

• 한국균학회지
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• 제27권4호통권91호
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• pp.312-317
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• 1999

우리나라 중요한 식품 원료인 전통 매주로부터 분리한 단독균의 접종 메주의 암세포 저해효과를 검색하기 위하여, 민간유래의 혈액암 세포주에 대한 저해활성을 MTT assay로 분석하였다. 먼저 전통 메주로부터 21종의 단독균을 분리한 후 각각 접종하여 발효된 단독균의 메주시료를 조제한 다음 80% methanol로 추출하였다. 메주 메탄올추출물은 혈액암세포중 HL60에서는 다소 낮은 성장 저해효과를 보였으나, U937과 Jurkat cell에서는 저해효과가 큰 것으로 나타났다. 특히 Mucor속과 Absidia속 Aspergillus속으로 제조된 메주들에서 이들 혈액암세포에 대해 저해효과가 큰 것으로 나타났다. 그러나 모든 메주 메탄올추출물들은 인간의 정상 lymphocyte에서 대해서는 90% 이상의 높은 생존율을 나타내어 정상 세포에 대한 성장 저해 효과가 거의 없음을 보며주었다. 이는 단독균의 메주시료가 가지는 세포독성이 암세포에 대한 특이적인 작용인 것으로 나타났다.

• Archives of Pharmacal Research
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• 제17권6호
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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.