Hodges J C, Remers W A, Bradner W T
J Med Chem. 1981 Oct;24(10):1184-91. doi: 10.1021/jm00142a013.
A series of 1-substituted mitosene analogues of the mitomycin antitumor antibiotics was prepared by total synthesis and screened for activity against P388 leukemia in mice. In general, analogues with moderately good leaving groups (mostly esters) at the 1 position were active, whereas analogues without such substituents were inactive or barely active. These results lend support to the idea that mitosenes with leaving groups at position 1 are capable of bifunctional alkylation of DNA in a manner similar to that of mitomycin C. The most active mitosenes were equal in potency (minimum effective dose) to a corresponding aziridinomitosene, but they were less effective in prolonging life span.
通过全合成制备了一系列丝裂霉素抗肿瘤抗生素的 1-取代丝裂烯类似物，并对其抗小鼠 P388 白血病的活性进行了筛选。一般来说，在 1 位具有适度良好离去基团（大多为酯）的类似物具有活性，而没有此类取代基的类似物则无活性或活性极低。这些结果支持了这样一种观点，即 1 位带有离去基团的丝裂烯能够以类似于丝裂霉素 C 的方式对 DNA 进行双功能烷基化。活性最高的丝裂烯在效力（最小有效剂量）上与相应的氮丙啶丝裂烯相当，但在延长寿命方面效果较差。
