Abstract

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 (LLC) cells and human Jurkat leukemia wild-type (JLC) 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.

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