Cytotoxicity and Antitumour Activity of Diphosphine Ligands

Many analogues of dppe have also been evaluated for antitumour activity against ip. P388 leukaemia These results are summarised in Table 10. In general replacement of phenyl- substituents for other groups resulted in a reduction in antitumour activity. Only 

It must be remembered that many of these diphosphines will be very readily oxidised under biologically relevant conditions. Although it may be possible to interpret these results in terms of differences in structure of the diphosphines, the biological activities may also reflect differences in the ease of oxidation and consequent detoxification. The apparent lower toxicity and reduced spectrum of antitumour activity of dppe in the earlier study seems likely to have been due to the partial oxidation of the tested compound. Available data on phosphine oxides show them to be inactive as antitumour agents (Ref 89 and NCI data). The bisoxide of dppe, Ph2(0)PCH2CH2P(0)Ph2, is inactive against P388 leukaemia, and has a lower toxicity in mice maximum tolerated dose (MTD) 300 pmol/kg, compared to 50 pmol/kg for dppe  

2 Cytotoxicity and Antitumour Activity of Linear, Bridged Digold Diphosphine Complexes 

SCSOEt, SGlu, SGal SMan, dppe(2Cr), SCH2CH(NH2)COOEt, PEt3(2NOj)  

It is notable that there is a similar trend between the degree of antitumour activity of the complexes and the length of the diphosphine (P-P) bridge Jo that observed for the ligands alone (Fig. 19). In addition, in the series XAu(dppe)AuX, the level of antitumour activity is influenced by the nature of the ligand X trans to P (Table 11). 

---