Antitumour activity of some cyclophosphazenes

Structures of inorganic rings as antitumor agents. II. Structure of the benzene clathrate of 2,2,4,4,6,6-hexa(1-aziridinyl)cyclotri(phosphazene), N3P3az6

“…0567-7408/82/010168-04501.00 comas (colon, Lewis lung, Yoshida) and other tumors (P815 mastocytoma, ependymoblastoma) has been reported recently (Labarre et al, 1978;Labarre, Faucher, Levy, Sournies, Cros & Francois, 1979). A greatly enhanced activity against some of these tumors (P388, L1210, B16) has also been observed for the three aziridinylcyclo(phosphathiazene) derivatives, N3P2S(O)Raz 4 (R = F, Ph, az) (Labarre, Sournies, van de Grampel & van der Huizen, 1979).…”

The first example of a cyclophosphazene `anticlathrate structure': geometry of 2,2,4,4,6,6-hexa(1-aziridinyl)cyclotri(phosphazene), N3P3az6, from an X-ray investigation of the complex N3P3az6.3CCl4

“…We recently reported the discovery of antitumor properties exhibited by some aminocyclophosphazenes, namely NaP3az 6 (az = 1-aziridinyl), N4P4az 8 and N4P4pyrro 8 (pyrro = pyrrolidinyl), against murine L 1210 and P 388 leukemias and B16 melanoma Labarre, Faucher, Levy, Sournies, Cros & Francois, 1979); in each case the most active appeared to be -as well as against line 26 colon carcinoma, Lewis lung carcinoma, ependymoblastoma, P 815 mastocytoma (Spreafico & Labarre, 1978) and Yoshida sarcoma (Fox & Labarre, 1978)the title compound N3Paaz 6 and, consequently, we were urged to investigate the X-ray crystal structure of this new antitumor agent, particularly inasmuch as the Ames tests, performed within the series (Lecointe & Labarre, unpublished), had proved that the origin of the activity could be reasonably searched for within a 'twobody' (drug versus target) assumption: N3P3az ~ was indeed found to be slightly mutagenic either with or without microsomes, supporting the idea that the drug does not need any intermediate metabolization to be effective.…”

Cytostatic Activity of Inorganic Heterocycles in an in vitro Screening System

“…From these experiments (NPAz2)2NSOPh appears to be the least active form corresponding with the results of the present study. Also the in vivo active compounds N 3P3Az6 (Apholate) [7,8] (table II) and N 3P3Az5Morph (Fotrin) [9] very clearly exhibit their cytostatic activity in the mi crotiter test plate method. In this context it is worth mentioning that, when applying this method, a cor relation with in vivo data can only be expected if the drug has not to be metabolized to some active form.…”