Cytotoxic agents: III, derivatives of ethyleneimine.

In Parts I and II of this series (Hendry, Rose, and Walpole, 1951; Hendry, Homer, Rose, and Walpole, 1951) we described the cytotoxic and tumour-inhibitory properties exhibited by certain polymethylolamide and bis-epoxide derivatives. Substances of these types were selected because of their use in textile technology in modifying the properties of fabrics. They are believed to bring about their peculiar effects by the formation, by virtue of their polyfunctional reactivity, of covalent linkages across the cellobiose or peptide chains of the textile fibres. It seemed not unlikely that the specific biological effects of these compounds were manifestations of a similar behaviour within the cell, and it was suggested that here the affected system was either protein or nucleoprotein, possibly of nuclear origin, since chromosome damage in dividing cells seemed to underlie the more significant features of their action. Compounds of a third chemical type were known to us to have applications similar to those of the methylolamides and epoxides in the textile field, and indeed were already under investigation in that connexion by our colleagues in these laboratories. These compounds were based on ethyleneimine (II), which in its chemical reactivities closely resembles the analogous ethylene oxide (I) molecule. The simple parent substance, like ethylene oxide, itself produces modifications in the physical properties of fibres, but the most effective agents in this series contain two or more imine residues, just as the most useful epoxides contain two epoxide groups. It is perhaps worthy of note at this point that the most convenient mode of combination of the imine residues in the molecule is usually through a linkage at the nitrogen atom (III), whereas the epoxide groups must necessarily be combined through a group attached to one of the carbon atoms (IV).