2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline (tmq), a potent non-classical folate antagonist inhibitor--I effect on dihydrofolate reductase and growth of rodent tumors in vitro and in vivo.
2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline (tmq), a potent non-classical folate antagonist inhibitor--I effect on dihydrofolate reductase and growth of rodent tumors in vitro and in vivo.
复制标题
2,4-二氨基-5-甲基-6-[(3,4,5-三甲氧基苯胺基)甲基]喹唑啉(tmq)，一种有效的非经典叶酸拮抗剂抑制剂--I对二氢叶酸还原酶和啮齿动物肿瘤生长的影响
DOI：
10.1016/0006-2952(79)90655-5
复制
发表时间：
1979
影响因子：
5.8
通讯作者：
E. Elslager
中科院分区：
文献类型：
--
作者：
J. Bertino;W. L. Sawicki;B. Moroson;A. Cashmore;E. Elslager
研究了17种非经典2,4-二氨基-6-[（苯胺）甲基]喹唑啉抗叶酸盐作为L1210白血病细胞和人白血病细胞（急性淋巴细胞白血病）中二氢叶酸还原酶的抑制剂。发现了几种有效的抑制剂，其中一些抑制剂的i50值为10−9M，因此显示出与甲氨蝶呤相当的活性。总的来说，抑制二氢叶酸还原酶的效力与体外对L1210细胞生长的抑制有关。其中两种化合物，化合物14(2,4-二氨基-5-甲基-6-[（3,4,5-三甲氧基苯基）甲基]喹唑啉；TMQ, JB-11, NSC 249008)和化合物3(2,4-二氨基-5-氯-6-[（3,4-二氯苯胺）甲基]喹唑啉；NSC 208652)，进一步对小鼠肿瘤进行了体内评价，均显示出广谱的抗肿瘤作用。这些研究的结果鼓励进一步评估这些化合物，特别是化合物14，作为治疗人类疾病的可能的抗肿瘤药物。
Seventeen non-classical 2,4-diamino-6-[(anilino)methyl]quinazoline antifolates were tested as inhibitors of dihydrofolate reductase from L1210 leukemia cells and from human leukemia cells (acute lymphocytic leukemia). Several potent inhibitors of this enzyme were found, some with I50values of 10−9M, thus displaying activity comparable to that of methotrexate. In general, the potency of dihydrofolate reductase inhibition correlated with the inhibition of cell growthin vitroagainst L1210 cells. Two of these compounds, compound 14 (2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline; TMQ, JB-11, NSC 249008) and compound 3 (2,4-diamino-5-chloro-6-[(3,4-dichloroanilino)methyl]quinazoline; NSC 208652), were further evaluated against murine tumorsin vivoand both showed a broad spectrum of antitumor effects. The results of these studies encourage further evaluation of these compounds, in particular compound 14, as possible anti-neoplastic agents in the treatment of human disease.