The Korean Journal of Pharmacology (대한약리학회지)

The Korean Society of Pharmacology (대한약리학회)
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Benzylacyclouridines ad Nucleoside Transport Inhibitors in Human Erythrocytes

Benzylacyclouridines의 적혈구에 있어서 Nucleoside 수송 억제

  • Lee, Kang-Hyun (Laboratory of Pharmacology, College of Medicine, Dong-A University,Korea and Division of Biology and Medicine, Brown University) ;
  • Cha, Sung-Man (Laboratory of Pharmacology, College of Medicine, Dong-A University,Korea and Division of Biology and Medicine, Brown University)
  • 이강현 (동아대학교 의과대학 약리학교실,브라운대학 의과대학 약리학교실) ;
  • 차승만 (동아대학교 의과대학 약리학교실,브라운대학 의과대학 약리학교실)
  • Published : 1988.06.30
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Abstract

Various Benzylacyclouridine (BAU, HM-BAU, suc-BAU, BBAU, HMBBAU, suc-BBAU, and BBBAU) developed as specifc inhibitors of uridine phosphorylase (UrdPase), inhibit transport (zero-trans influx) of ridine (Urd) in human erythrocytes. The inhibition pattern of these compounds is competitive, though suc-BBAU and BBBAU show a slight noncompetivieness. The order of potency as an inhibitor of the nucleoside transport system is BBAU ${\sim}$ HM-BBAU ${\sim}$ suc-BBAU > BBBAU > BAU ${\sim}$ suc-BAU ${\sim}$ HM-BAU ($K_1$ values of 19, 23, 38, 112, 124, 174 and 176 ${\mu}M$, respectively). These data indicate that there is a differnece in potency of Urd transport inhibition between the analogs of BAU and BBAU. Further, the potency correlates with the hydrophobicity of the compound, but it has a limit in the size of $C_5$ substitution. Abbreviation: BAU (5-benzylacyclouridine), 5-benzyl-1-(2'-hydroxyethoxymethyl) uracil; HM-BAU (3'-hydroxymethyl-BAU), 5-benzyl-1- [(1',3'-dihydroxy-2-propoxy) methyl]uracil; suc-BAU, 3'-succinyl-BAU; BBAU (benzyloxybenzylacyclouridine), 5-( m-benzyloxybenByl)-1-(2'-hydroxyethoxymethyl)uracil; HM-BBAU (3'-hydroxymethyl-BBAU), 5-(m-benzyloxybenzyl)-1- [(1'3'-dihyd.oxy-2-p.epoxy)methyll u.acil; suc-BAU, 3'-succinyl-BBAU; BBBAU, 5- f 3-(4-benzyloxyben-Eyl)benzyll -1-(2'-hydroxyethoxymethyl)uracil; Urdpase, uridine phosphorylase; Urd, Uridine; Fd-Urd, 5-fluoro-2'-deoxyuridine; AcThd, aoyclothyrnidine; AcUrd, acyclouridine; dThd, thymidine; NBMPR, nitrobenzylthioisone; FUra, 5-fluorouracil.

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.

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