Toxicity and Antitumor Properties of N3P3 MeAz

Toxicity measurements were performed in a classical way on DBA/2 mice and LDq was found to be 250 mg/kg. We may notice that MYKOMET 63 is about six times less toxic than MYKO 63. 

For L 1210 10 cells implanted i.p. for P 388 10 cells implanted i.p. i.p. treatment (10 to 15 mice per group) generally one day after the graft of cells drugs were dissolved in 0.9% NaCl solution. 

In Table 8 are shown the activities of MYKOMET 63 under various conditions against murine (DBA/2 mice) P388 and L1210 leukemias, compared with the ones reported previously for MYKO 63. 

The comparison of the two sets of %ILS values allows us to conclude that MYKOMET 63 appears to be actually as active as MYKO 63, but not more active. In other words, the graft of methylated aziridinyl ligands on a six-membered cyclophosphazene ring does not significantly improve the antitumoral activity with respect to the non-methylated isologues. However, because MYKOMET 63 possesses only a slight toxicity compared to MYKO 63, the new drug reported here may be of interest for eventual clinical use, no matter what difficulties are encountered in its synthesis. 

We shall see in the next paragraph, that this approach brought about the improvements we were looking for. 

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