Kishi K, Yazawa K, Takahashi K, Mikami Y, Arai T
J Antibiot (Tokyo). 1984 Aug;37(8):847-52. doi: 10.7164/antibiotics.37.847.
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 either 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 our proposed model for the saframycin A-DNA adduct.
为了研究构效关系，利用已建立的对13种苦霉素（包括强效抗肿瘤成分苦霉素A）高度敏感的L1210小鼠白血病细胞系，测定了它们的体外抗肿瘤活性。缺少α-氰基胺基团或α-氨基醇基团的苦霉素表现出比苦霉素A低得多的细胞毒活性。在基本骨架的C-14位或侧链的C-25位用大体积取代基修饰活性苦霉素，会导致细胞毒活性降低。这些构效关系证实了所提出的苦霉素A抗肿瘤活性的主要作用机制，并支持了我们提出的苦霉素A-DNA加合物模型。
