• Biomolecules & Therapeutics
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• 제3권2호
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• pp.116-121
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• 1995

Some multidrug resistance inhibitors have been known to be influenced by the serum concentration. In this study, effect of serum concentration on inhibition of nucleoside transport by BIBW22, a new multidrug resistance inhibitor derived from dipyridamole (DPM), was studied. When 5% or 100% (v/v) of fetal bovine serum (FBS) was contained in the culture, DPM dose for which nucleoside transport was inhibited by 50% (lD$_{50}$) was 0.42 $\mu$M or 1.17 $\mu$M, respectively. BIBW22 also showed the same trend as DPM did in response to increase of FBS concentration. However, ID$_{50}$ value for DPM in the absence or presence of human plasma was 0.007 $\mu$M or 1.02 $\mu$M respectively showing 145 times increase of ID$_{50}$ value. ID$_{50}$ value for BIBW22 in the presence of human plasma was 0.028 $\mu$M showing only 5 times increase in ID$_{50}$ value. This result suggests that potency of BIBW22 was much less affected by the plasma concentration and BIBW22 could be a good candidate for a clinical use in multidrug resistance treatment.treatment.

• 대한약리학회지
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• 제24권1호
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• pp.11-16
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• 1988

Uridine phosphorylase 효소의 강력한 억제제로 개발된 유리딘 비고리핵산들(Benzylacyclouridine: BAU, HM-BAU, suc-BAU, BBAU, HM-BBAU, suc-BBAU, and BBBAU)이 uridine,의 사람 적혈구 내로의 수송(Zero-trans influx)에 미치는 영향에 관하여 rapid sampling technique을 이용하여 고찰하였다. 이 실헙에서 유리딘-비고리핵산들은 parent compounds인 BAU, BBAU와 같이 uridine 수송에 상경적인 억제작용을 보였다. 그러나 suc-BBAU와 BBBAU는 비상경적인 억제요소도 나타냈다. Uridine 수송억제제로서 효력의 크기는 $BBAU{\sim}HM-BBAU{\sim}suc-BBAU>BAU{\sim}suc-BAU{\sim}HM-BAU$이었으며, 그 억제상수는 각각 19, 23, 38, 112, 124, 174 그리고 $176\;{\mu}M$이었다. 본 실험 결과에서는 uridine 수송에 있어서 BAU의$C_5$ 자리의 친지방성 치환 group의 크기에 따라 억제효력이 다른 것이 시사되었다.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.158-159
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• 2003

We have cloned and functionally expressed a sodium dependent human nucleoside transporter, hCNT2, from a CNS cancer cell line U251. Our cDNA clone of hCNT2 had the same predicted amino acid sequence as the previously cloned hCNT2 transporter. Of the several cell lines studied, the best hCNT2 transport function was obtained when transiently expressed in U251 cells.(omitted)

• 대한약리학회지
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• 제26권1호
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• pp.91-100
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• 1990

Benzylacyclouridines (BAU and BBAU)는 uridine phosphorylase (UrdPase)의 선택적이고 강력한 상경억제제이다. 보고된 바에 의하면 (Cancer Res., 44: 1852, 1984) Benzylacyclouridines가 5-fluoro-2'-deoxyuridine (FdUrd)의 인체 암세포에 대한 독성을 증가시켜 준다고 하였지만, L5187Y 세포를 사용한 본 실험에서는 Benzylacyclouridines가 FdUrd를 포함하여 5-fluorouridine (FUra) 모두에 대해 조금도 세포 독성을 증가시키지 못하였을 뿐만아니라, 오히려 세포를 그들 독성으로부터 투여량에 비례하여 보호하였다. 복강내 주사에 의한 생체실험에서도 Benzylacyclouridines는 5-fluorinated pyrimidine에 의한 L5187Y를 지닌 쥐(mouse)의 life-span을 연장시켜 주지 못하였다. 본 실험에서 Benzylacyclouridines가 기대했던 fluorinated pyrimidine 항암제의 효과를 증진시키지 못한 이유는 nucleosides의 anabolism이 UrdPase와 orotate phosphoribosyltransferase이 의한 sequential 작용에 의하던가 또는 Benzylacyclouridines에 의한 nucleosides의 수송억제에 의하던가, 아니면 두가지 다 복합적으로 작용한 결과로 생각된다.

• Journal of Microbiology and Biotechnology
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• 제28권6호
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• pp.849-859
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• 2018

Herpes simplex virus type 2 (HSV-2) infection has been a public health concern worldwide. It is the leading cause of genital herpes and a contributing factor to cervical cancer and human immunodeficiency virus (HIV) infection. No vaccine is available yet for the treatment of HSV-2 infection, and routinely used synthetic nucleoside analogs have led to the emergence of drug resistance. The small molecule $Retro-2^{cycl}$ has been reported to be active against several pathogens by acting on intracellular vesicle transport, which also participates in the HSV-2 lifecycle. Here, we showed that Retro-2.1, which is an optimized, more potent derivative of $Retro-2^{cycl}$, could inhibit HSV-2 infection, with 50% inhibitory concentrations of $5.58{\mu}M$ and $6.35{\mu}M$ in cytopathic effect inhibition and plaque reduction assays, respectively. The cytotoxicity of Retro-2.1 was relatively low, with a 50% cytotoxicity concentration of $116.5{\mu}M$. We also preliminarily identified that Retro-2.1 exerted the antiviral effect against HSV-2 by a dual mechanism of action on virus entry and late stages of infection. Therefore, our study for the first time demonstrated Retro-2.1 as an effective antiviral agent against HSV-2 in vitro with targets distinct from those of nucleoside analogs.

• Journal of Chest Surgery
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• 제33권2호
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• pp.117-124
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• 2000

Background: Nucleoside transport inhibitor(NTI) Keeps AMP, ADP, ATP levels high in myocytes by inhibiting adenosine cataboilsm so that it may preserve the myocardial contractability during ischemia In this study we investigated the effects of cyclic AMP phosphodiesterase inhibor(C-AMP PDSI) and S-P-nitrobenzyl-6 -thioniosine(NBT; a sort of NIT) on myocadial preservation and changes of constituent enzyme. Material and method: Twenty-six isolated rabbit hearts were perfused with Krebs-Henseleit buffer solution for 20 minutes arrested for 20 minutes and ten reperfused for 30 minutes. The following four groups were prepared and hemodynamic changes coronary effluent lactate dehydrogenase (LDH) a-hydroxybutylic accid(a-HBD) levels and myocardial LDH creatine kinase-MB (CK-MB) adenosine deaminase(ADA) a-HBD levels and myocardial LDH creatine kinase-MB (CK-MB) adenosine deaminase(ADA) a-HBD levels were analysed before and after cardiac arest ; Group I(control) ; the heart was only perfused with K-H ; Group II ; the heart was perfused with K-H including C-AMP PDSI(Amrinone 25mg/L); Group III ; the heart was perfused with K-H including NBT(4.19mg/L) ; Group IV ; the heart was perfused with K-H including C-AMP PDSI + NBT. Result : Left venticular developed pressure(LVDP) at 10 minutes of the equilibrium was significantly higher in group III(72.1$\pm$5.3 mmHg p<0.01) and group III(72$\pm$5.6 mmHg P<0.025) as compared with group I (40.8$\pm$4.7mmHg) and LVDP at 20 minutes of the reperfusion was significantly higher in group II(74$\pm$5.3mmHg p<0.01) and group III(72$\pm$5.6mmHg p<0.025) as compared with group I (44.2$\pm$4.6mmHg). Percentage recovery of LVDP at the reperfusion was the highest in group II(123.3%) Percentage recovery of coronary flow at the equilibrium reperfusion were higher in group II(310%, 270%) group III(230%, 290%) group IV(310%, 280%) as compared with group I (100%) respectively. Myocadial LDH level was significant lower in group IV(33495$\pm$1802 IU/gm p<0.04) as compared with group I(48767$\pm$1421 IU/gm) Myocadial CK-MB level was significant higher in group II(74820$\pm$1421 IU/gm) compared with group I (45450$\pm$1737 IU/gm) Myocadial ADA level was significant higher group IV(1215$\pm$8 IU/gm p<0.05) compared with group I(125$\pm$15 IU/gm) but there was no significant difference between group I and group II ,III, IV in changes of coronary effluent LDH, a-HBD levels. Conclusion: C-AMP PDSI solely appears to have a better effect on myocardial preservation after ischemia than NBT but with no synergistic effect and it could keep CK-MB leve high in myocardial tissues.