Collier D A, Neidle S
Cancer Research Campaign Biomolecular Structure Unit, Institute of Cancer Research, Sutton, Surrey, U.K.
J Med Chem. 1988 Apr;31(4):847-57. doi: 10.1021/jm00399a028.
A series of 1- and 1,4-substituted amidoanthraquinones have been prepared, with side chains possessing basic nitrogen atoms. Computer modeling and energy calculations have shown that all eight compounds can bind intercalatively to DNA and that there are significant differences in the additional nonbonded and electrostatic interactions possible at the DNA binding site. Solution DNA binding and closed-circular DNA unwinding studies confirmed intercalative interactions, and the predicted differences in strength of interactions between mono- and disubstituted compounds were found. All compounds were modestly cytotoxic to L1210 cells in culture. In vivo activity against L1210 and S180 tumors was not found for the monosubstituted compounds, whereas the four disubstituted ones had varying levels of measurable, though low, activity.
已经制备了一系列具有含碱性氮原子侧链的1-和1,4-取代的酰胺基蒽醌。计算机建模和能量计算表明，所有八种化合物都可以以插入方式与DNA结合，并且在DNA结合位点可能存在的额外非键合和静电相互作用方面存在显著差异。溶液DNA结合和闭环DNA解旋研究证实了插入相互作用，并且发现了单取代和双取代化合物之间预测的相互作用强度差异。所有化合物在培养中对L1210细胞均具有适度的细胞毒性。单取代化合物在体内对L1210和S180肿瘤没有活性，而四种双取代化合物具有不同程度的可测量的低活性。
