It may be seen that dFU-.V-IIP has a greater activity on these cells than dFU-.'J'-IIP. Figure 1 permits a comparison of the effectiveness of the compounds on a molar equivalent, instead of milligram basis as used in the calculation of II),W values. Comparative ratios (treated cells: control cells) calculated from data obtained on dav 3 at a drug concentration of 10.1/, are FUI Ml, 0.11; dFU-V-IIP, O.oS ; dFU-.V-IIP, 0.14 or 11.0+.VJ.O'U, and 140,' inhibition of control cell growth, respectively. I >ay 3 was chosen because by the 4lh day there may be some loss of cells, especially in the control tubes, due to overcrowding and exhaustion of nutrients from the media. In addition. a< anticipated theoretically, dFU-.V-IIP was hydrolyzed during cell growth to the purple-blue diiodoindigo which could be observed microscopically inside the cells.
Twelve 1,4-naphthoquinones have been tested against the ascitic form of sarcoma 180 in Swiss mice. Statistical analysis shows that the most important molecular parameter determining their effectiveness in prolonging the life of mice bearing this tumor is their redox potentials. Although the toxicities of the compounds are also related to the redox potentials in the same way, the therapeutic indexes can be increased by adding substituents of greater lipophilicity. The naphthoquinones differ greatly in antitumor activities and may inhibit the growth of malignant cells by different mechanisms.
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