Sosnovsky G, Rao N U
Cancer Lett. 1986 Aug;32(2):155-64. doi: 10.1016/0304-3835(86)90114-x.
The structure-anticancer activity and the activity-lipophilicity relationship of 8 mono- and bis-anthraquinone hydrazones containing the N,N;N',N'-bis(1,2-ethanediyl) phosphoric diamide moiety were evaluated. These compounds were tested in vivo, using murine lymphocytic leukemia P388. Seven of these compounds were active and one was marginal at optimum doses. The highest activity was exhibited by the bis[N,N;N',N'-bis(1,2-ethanediyl)-[N2-(1',4',5',8'-tetrahydroxy anthracenylidene)-N1-methyl hydrazin-1-yl]]-phosphoric triamide, bis[N,N;N',N'-bis(1,2-ethanediyl)-[N2-(1',4'-dihydroxy anthracenylidene)-N1-methylhydrazin-1-yl]]phosphoric triamide and bis-[N,N;N',N'-bis(1,2-ethanediyl)-[N2-(1',4',5',8'-tetrahydroxy anthracenylidene)-N1-phenylhydrazin-1-yl]]phosphoric triamide as is evidenced by their percent T/C of 183, 175 and 172, respectively. The correlation of the anticancer activities of these compounds with their lipophilicities leads to the general hypothesis that the intercalating and alkylating capabilities of a potential drug may play only a secondary role as compared to the selective permeability of the drug through normal and cancerous membranes.
对8种含有N,N;N',N'-双(1,2 - 乙二基)磷酸二酰胺部分的单蒽醌腙和双蒽醌腙的结构 - 抗癌活性及活性 - 亲脂性的关系进行了评估。这些化合物在体内使用小鼠淋巴细胞白血病P388进行了测试。其中7种化合物具有活性，1种在最佳剂量下表现为边缘活性。双[N,N;N',N'-双(1,2 - 乙二基)-[N2-(1',4',5',8'-四羟基蒽亚基)-N1-甲基肼-1-基]]-磷酸三酰胺、双[N,N;N',N'-双(1,2 - 乙二基)-[N2-(1',4'-二羟基蒽亚基)-N1-甲基肼-1-基]]磷酸三酰胺和双-[N,N;N',N'-双(1,2 - 乙二基)-[N2-(1',4',5',8'-四羟基蒽亚基)-N1-苯基肼-1-基]]磷酸三酰胺表现出最高活性，其T/C百分比分别为183、175和172。这些化合物的抗癌活性与其亲脂性的相关性得出一个普遍的假设，即与药物通过正常和癌细胞膜的选择性通透性相比，潜在药物的嵌入和烷基化能力可能仅起次要作用。
