Garg R, Denny W A, Hansch C
Chemistry Department, Pomona College, Claremont, CA 91711-6338, USA.
Bioorg Med Chem. 2000 Jul;8(7):1835-9. doi: 10.1016/s0968-0896(00)00114-0.
Quantitative structure-activity relationships have been formulated for two sets of DNA binding topoisomerase agents (bis-acridines and bis-phenazines) acting on murine P388 leukemia cells, murine Lewis lung carcinoma (LL(C)) cells and human Jurkat leukemia wild-type (JL(C)) cells. For the acridines, all three QSARs (1-3) show only a (small negative) hydrophobic effect. In sharp contrast, the phenazines in all three studies (4-6) show a strong hydrophobic effect, with the optimum ClogP being near 7.3 for all examples. This suggests that, despite the structural similarity of the compounds, different modes of enzyme and/or DNA binding may be involved.
已经针对作用于小鼠P388白血病细胞、小鼠Lewis肺癌（LL(C)）细胞和人Jurkat白血病野生型（JL(C)）细胞的两组DNA结合拓扑异构酶试剂（双吖啶和双吩嗪）建立了定量构效关系。对于吖啶类，所有三个定量构效关系（1-3）仅显示出（小的负）疏水效应。与之形成鲜明对比的是，在所有三项研究（4-6）中，吩嗪类均显示出强烈的疏水效应，所有实例的最佳ClogP接近7.3。这表明，尽管这些化合物结构相似，但可能涉及不同的酶和/或DNA结合模式。
