Supino R, Necco A, Dasdia T, Casazza A M, Di Marco A
Cancer Res. 1977 Dec;37(12):4523-8.
Four new derivatives of daunorubicin and two new derivatives of Adriamycin characterized by the absence of the methoxyl groups at the C-4 position have been studied in cell cultures in vitro to establish structure-activity relationships. 4-Demethoxydaunorubicin was 27 to 100 times more active than was daunorubicin when inhibiting the cloning efficiency of exponential-phase HeLa cells and, like daunorubicin, was slightly active on early plateau-phase cells. DNA synthesis in mouse embryo fibroblasts stimulated by fetal calf serum was inhibited equally by the two compounds, although 4-Demethoxydaunorubicin was slightly more active than was daunorubicin when inhibiting RNA synthesis. The beta anomer of 4-demethoxydaunorubicin showed a reduced activity on HeLa cells compared to its alpha anomer, but it was equally active on DNA synthesis. The stereoisomers of 4-demethoxydaunorubicin bearing the inverted configuration in positions 7 and 9 were devoid of significant cytotoxic activity and were only slightly active on DNA synthesis at the doses tested. 4-demethoxyadriamycin and 4-demethoxy-4'-epi-adriamycin were 65 to 500 times more active than was Adriamycin on HeLa cell cloning efficiency and about 10 times more active on DNA synthesis in mouse embryo fibroblasts. Cell uptake in mouse embryo fibroblasts was also investigated for all the new derivatives tested.
对柔红霉素的四种新衍生物和阿霉素的两种新衍生物进行了体外细胞培养研究，以建立构效关系，这些衍生物的特征是在C-4位没有甲氧基。在抑制指数生长期的HeLa细胞的克隆效率时，4-去甲氧基柔红霉素的活性比柔红霉素高27至100倍，并且与柔红霉素一样，对早期平台期细胞的活性较弱。两种化合物对胎牛血清刺激的小鼠胚胎成纤维细胞中的DNA合成抑制作用相同，尽管在抑制RNA合成时4-去甲氧基柔红霉素的活性略高于柔红霉素。与α-异头物相比，4-去甲氧基柔红霉素的β-异头物对HeLa细胞的活性降低，但对DNA合成的活性相同。在7和9位具有反向构型的4-去甲氧基柔红霉素的立体异构体没有明显的细胞毒性活性，并且在测试剂量下对DNA合成的活性仅略高。4-去甲氧基阿霉素和4-去甲氧基-4'-表阿霉素对HeLa细胞克隆效率的活性比阿霉素高65至500倍，对小鼠胚胎成纤维细胞中的DNA合成的活性高约10倍。还对所有测试的新衍生物在小鼠胚胎成纤维细胞中的细胞摄取进行了研究。
