Inhibitory Effects of Pyrimidine, Barbituric Acid and Pyridine Derivatives on 5-Fluorouracil Degradation in Rat Liver Extracts
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- TATSUMI Kunihiko
- Biwako Research Institute, Otsuka Pharmaceutical Co., Ltd.
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- FUKUSHIMA Masakazu
- Biwako Research Institute, Otsuka Pharmaceutical Co., Ltd.
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- SHIRASAKA Tetsuhiko
- Biwako Research Institute, Otsuka Pharmaceutical Co., Ltd.
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- FUJII Setsuro
- Biwako Research Institute, Otsuka Pharmaceutical Co., Ltd.
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The inhibitory effects of about 30 compounds, mainly pyrimidine and pyridine derivatives, on 5-fluorouracil degradation catalyzed by dihydrouracil dehydrogenase (DHU dehydrogenase) were investigated. The inhibitory activities of 5-substituted uracil derivatives decreased time-dependently during preincubation with liver extracts, indicating that these compounds are substrates of DHU dehydrogenase. During preincubation, 4, 6-dihydroxypyrimidine derivatives were found to be converted to barbituric acid derivatives, which have stronger activities. The inhibitory activity of 2, 4-dihydroxypyridine (3-deazauracil), which was stronger than that of uracil, did not change during preincubation, indicating that this compound is not a substrate but is an inhibitor of DHU dehydrogenase, and suggesting that 2, 6-dihydroxypyridine (1-deazauracil) could be a potent inhibitor. In the light of these findings, we examined various derivatives of barbituric acid, 2, 4-dihydroxypyridine and 2, 6-dihydroxypyridine. Among these compounds, 3-cyano-2, 6-dihydroxypyridine and 5-chloro-2, 4-dihydroxypyridine were the strongest inhibitors with Ki values for DHU dehydrogenase of 2.3×10-7M and 3.6×10-7M, respectively.
収録刊行物
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- Japanese Journal of Cancer Research GANN
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Japanese Journal of Cancer Research GANN 78 (7), 748-755, 1987
日本癌学会
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詳細情報 詳細情報について
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- CRID
- 1390282681283073408
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- NII論文ID
- 130007311252
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- ISSN
- 09105050
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可