Mitomycin C and porfiromycin analogues with substituted ethylamines at position 7.
Mitomycin C and porfiromycin analogues with substituted ethylamines at position 7.
复制标题
丝裂霉素 C 和卟啉霉素类似物，在 7 位上有取代的乙胺。
DOI：
10.1021/jm00355a004
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发表时间：
1983
影响因子：
7.3
通讯作者：
Schurig,JE
中科院分区：
文献类型：
--
作者：
Iyengar,BS;Sami,SM;Remers,WA;Bradner,WT;Schurig,JE
在标准抗肿瘤系统中制备并筛选了一系列丝裂霉素 C 和卟啉霉素的 7-（2-取代-乙基）氨基类似物。这些类似物中的某些类似物对小鼠中的 P-388 白血病、L-1210 白血病和/或 B-16 黑色素癌表现出比丝裂霉素 C 更好的活性。还测试了化合物在小鼠中的白细胞减少作用，即丝裂霉素C的限制毒性。与该临床药物相比，其中一些化合物的白细胞减少程度较轻，有些则白细胞减少程度更高。类似物的理化性质和抗肿瘤活性之间没有统计学上显着的相关性。在本系列的前一篇文章中，我们将丝裂霉素类似物开发的目标定义为制备在 P-388 白血病中至少与丝裂霉素 C 一样有效的化合物，但其引起的白细胞减少症显着减少。选择新的7位取代化合物是因为7位控制醌环的还原，从而提供了在正常细胞和某些癌细胞之间获得一定选择性的机会。在本文中，探索了丝裂霉素 C 和卟啉霉素 7-氨基上的取代基的多种结构类型。许多新的先导化合物被确定为未来类似物开发的目标，并考虑了初步的结构-活性关系。 1
A series of 7-(2-substituted-ethyl) amino analogues of mitomycin C and porfiromycin was prepared and screened in standard antitumor systems. Certain of these analogues showed better activity than mitomycin C against P-388 leukemia, L-1210 leukemia, and/or B-16 melanocarcinoma in mice. Compounds also were tested for their leukopenic effects in mice, the limiting toxicity ofmitomycin C. Some of them were less leukopenic and some were more leukopenic than this clinical agent. No statistically significant correlations could be made betweenphysicochemical properties and antitumor activitiesof the analogues.In the preceding article in this series, we defined the goal of mitomycin analogue development as the preparation of compounds that are at least as potent and efficaceous as mitomycin C in P-388 leukemia but which cause significantly less leukopenia. New 7-substituted compounds were chosen because position 7 controls the reduction of the quinone ring, thus offering a chance to gain some selec-tivity between normal cells andcertain cancer cells. In this article, a variety of structural types were explored as substituents on the 7-amino group of mitomycin C and porfiromycin. A number of new lead compounds were identified as the targets for future analogue development, and preliminary structure-activity relationships were considered. 1