STRUCTURE-ACTIVITY-RELATIONSHIPS OF SAFRAMYCINS
STRUCTURE-ACTIVITY-RELATIONSHIPS OF SAFRAMYCINS
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DOI：
10.7164/antibiotics.37.847
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发表时间：
1984-01-01
影响因子：
3.3
通讯作者：
ARAI, T
中科院分区：
文献类型：
--
作者：
KISHI, K;YAZAWA, K;ARAI, T
本文用已建立的高敏感性小鼠白血病细胞系L1210测定了13种番红花霉素类化合物的体外抗肿瘤活性，并对其构效关系进行了研究。缺乏α-氨基葡萄糖的Saframycins氰基胺基团或α-甲醇胺组细胞毒活性明显低于沙夫霉素A组。在基本骨架上的C-14位置或在侧链上的C-25位置处用大体积取代基对活性saframycins进行修饰导致细胞毒活性降低。这些构效关系证实了提出的主要作用机制的抗肿瘤活性的Saframycin A和支持一个建议的模型，为Saframycin A-DNA加合物。
In vitro antitumor activities of 13 saframycins, including the potent antitumor component, saframycin A, were determined with the highly sensitive established cell line of L1210 mouse leukemia to investigate structure-activity relationships. Saframycins which lack the .alpha.-cyanoamine group or the .alpha.-carbinolamine group exhibited much lower cytotoxic activity than saframycin A. The modification of active saframycins at the C-14 position on the basic skeleton or at the C-25 position on the side chain with bulky substituents resulted in a decrease in cytotoxic activity. These structure-activity relationships corroborated the proposed major mechanism of action for the antitumor activity of saframycin A and supported a proposed model for the saframycin A-DNA adduct.