2,3,5-Tris-ethylenimino-1,4-benzoquinone (Trenimon): some chemical and biological properties

The three aziridine rings of 2,3,5-tris-ethylenimino-1,4-benzoquinone (Trenimon) were found to be active alkylating centres in the presence of acid catalyst, but differed in reactivity among themselves. At a given pH Trenimon was readily reduced by a number of agents including cysteine, which probably formed a substitution derivative. The cysteine derivative possessed three alkylating groups which were more reactive than those of pure Trenimon. Trenimon was soluble in fat solvents but the reduction and substitution derivatives were not. Trenimon was bound to hemoglobin and to albumins, probably by a substitution reaction between a sulfhydryl group of the protein and the 6-carbon atom of the drug. Binding to globulin occurred only following reduction of the protein. Trenimon was readily taken up by L5178Y lymphoma cells in suspension culture and was highly toxic but the cysteine derivative was not readily taken up and was less toxic than Trenimon by three orders of magnitude. The implications of the solubility and other physical properties of the alkylating agents are discussed, and evidence is presented that the biologically effective concentration of a drug is that which binds to the cell surface.