Further studies on substituted quinazolines and triazines as inhibitors of a methotrexate-insensitive murine dihydrofolate reductase.
Further studies on substituted quinazolines and triazines as inhibitors of a methotrexate-insensitive murine dihydrofolate reductase.
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取代喹唑啉和三嗪作为甲氨蝶呤不敏感的鼠二氢叶酸还原酶抑制剂的进一步研究。
DOI：
10.1016/0006-2952(86)90151-6
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发表时间：
1986
影响因子：
5.8
通讯作者：
Goldie,JH
中科院分区：
文献类型：
--
作者：
Dedhar,S;Freisheim,JH;Hynes,JB;Goldie,JH
数据上的35喹唑啉和取代的三嗪化合物作为抑制剂的蛋氨酸不敏感形式的二氢叶酸还原酶纯化从蛋氨酸耐药L5178Y小鼠白血病细胞的系统分析。发现几种化合物比甲氨蝶呤更有效地抑制这种酶的活性。其中两种三嗪化合物的IC 50值接近10 nM，这与甲氨蝶呤对正常药物敏感的二氢叶酸还原酶的IC 50值接近。此外，这些化合物中的一些，特别是三嗪，与来自相同细胞系的正常的对甲氨蝶呤敏感的二氢叶酸还原酶相比，对甲氨蝶呤不敏感的酶表现出抑制特异性。因此，这些化合物可潜在地用于治疗那些表达改变的、对甲氨蝶呤不敏感的二氢叶酸还原酶的甲氨蝶呤抗性肿瘤。
Data are presented on the systematic analysis of thirty-five quinazoline and substituted triazine compounds as inhibitors of a methotrexate-insensitive form of dihydrofolate reductase purified from methotrexate-resistant L5178Y murine leukemia cells. Several of the compounds were found to be more potent inhibitors of this enzyme activity than was methotrexate. Two of the triazine compounds had IC50values approaching 10 nM, which is close to that of methotrexate for the normal drug-sensitive dihydrofolate reductase. In addition, some of these compounds, especially the triazines, exhibit a specificity of inhibition for the methotrexate-insensitive enzyme as compared to the normal methotrexatesensitive dihydrofolate reductase derived from the same cell line. These compounds may, therefore, be potentially useful in the treatment of those methotrexate-resistant tumours which express an altered, methotrexate-insensitive dihydrofolate reductase.