Bifunctional intercalators: relationship of antitumor activity of diacridines to the cell membrane.

The in vivo antitumor effectiveness [as measured by the percentage increase in life-span (ILS%)] of 28 diacridine bis-intercalators of nucleic acids shows a highly significant correlation with their effect on phenomena associated with plasma membrane as well as a high degree of structural specificity. In contrast, the ILS% does not correlate with the uptake of these diacridines by cells, nor with the inhibition of RNA synthesis or of DNA synthesis or with the inhibition of growth of cells in culture. The possibility that the antitumor effectiveness of actinomycin D, another DNA intercalator, is associated with sites of action other than the hibition of RNA synthesis is discussed.