FLUORINATED PYRIMIDINES, A NEW CLASS OF TUMOUR-INHIBITORY COMPOUNDS
FLUORINATED PYRIMIDINES, A NEW CLASS OF TUMOUR-INHIBITORY COMPOUNDS
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DOI：
10.1038/179663a0
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发表时间：
1957-01-01
期刊：
影响因子：
64.8
通讯作者：
SCHEINER, J
中科院分区：
文献类型：
--
作者：
HEIDELBERGER, C;CHAUDHURI, NK;SCHEINER, J
此外，I和II在体外对各种微生物，特别是革兰氏阴性菌显示出明显的抑菌作用。第三，效果不太好。一些相关化合物的合成和测试正在我们的实验室进行研究。迄今为止，5-氟-尿嘧啶和5-氟-乳清酸已证明对大鼠和小鼠中的以下移植肿瘤具有生长抑制活性：Flexner-Jobling癌，VValker 256癌肉瘤，Yoshida腹水瘤，Shay绿色白血病，肉瘤180，埃利希腹水癌，L-1210白血病，E0771，乳腺腺癌755，和肉瘤A-1（一种由二苯并蒽诱导的肿瘤衍生的可移植肉瘤; Buck，未发表）。典型实验的结果示于表1和表2中。在实体瘤的研究中，我们计算了它们的体积，而不是称重。这样做是为了重复测定，以评估肿瘤的生长速度和药物的作用持续时间。从表1中可以看出，在所有比较的情况下，5-氟-尿嘧啶比5-氟-乳清酸更有效。5-氟尿嘧啶对所有四种肿瘤的生长都产生了非常显著的抑制作用，重复给药比单次给药的效果更明显。这是在几乎没有毒性的剂量水平，如轻微的体重减轻所示。与此相反的是，
Moreover, I and II have shown an appreciable bacteriostatic effect in vitro against various micro-organisms, particularly Gram-negative bacteria. III was much less effective. The synthesis and testing of a number of related compounds are undergoing investigation in our laboratories. To date, 5-fluoro-uracil and 5-fluoro-orotic acid have demonstrated growth-inhibitory activity against the following transplanted tumours in rats and mice: Flexner-Jobling carcinoma, VValker 256 carcinosarcoma, Yoshida ascites tumour, Shay's chloroleukæmia, Sarcoma 180, Ehrlich ascites carcinoma, L-1210 leukæmia, E0771, mammary adeno-carcinoma 755, and Sarcoma A-1 (a transplantable sarcoma derived from a dibenzanthracene-induced tumour; Buck, unpublished). The results of typical experi-ments are shown in Tables 1 and 2. In the work with solid tumours we have calculated their volumes, instead of weighing. This was done so that the determinations could be made repeatedly in order to assess the growth-rate of the tumours and the duration of effect of the drugs. It will be noted from Table 1 that in all cases in which they have been compared, 5-fluoro-uracil is more effective than 5-fluoro-orotic acid. A very significant inhibition of growth of all four tumours was produced by 5-fluorouracil, and a more pronounced effect was observed with repeated rather than with single doses. This is at a dose-level at which there is little toxicity, as indicated by the slight weight loss. On the contrary,