Untersuchungen zum cytostatischen Wirkungsmechanismus der Methylhydrazine, II

Abstract

To elucidate the tumour-inhibiting action of the methylhydrazine derivatives, it was important to know whether hydrazine itself had a cytostatic action or whether this first occured after the introduction of the methyl group. Hydrazine, monobenzylhydrazine, and other non-methylated hydrazine derivatives inhibit "in vivo" tumour growth and reduce the incorporation rate of [14C]thymidine, [14C]uridine and [14C] leucine in ascites cells. Parallel experiments with the corresponding methylated hydrazines showed that the introduction of the methyl group increased the cytostatic effect. Previous experiments had led to the assumption that the degradation of dehydrogenated methylhydrazine produced cytostatically effective azomethine compounds and N-methylol compounds as well as formaldehyde, so that amino-alkylation and hydroxymethylation are to be expected. It is shown that all of the investigated methylhydrazine derivatives lose up to 35 percent of the theoretical formaldehyde in vitro after mild dehydrogenation with potassium hexacyanoferrate (HI). Formaldehyde is lost by methylazo and methylazoxy derivatives of Natulan (a methyl hydrazine compound) when they are suspended in a neutral aqueous solution. It is to be concluded that the donors of formaldehyde (Azomethine compounds and N-methylol compounds, see above), are also formed. Formalhydrazine, a potential degradation product of methylhydrazine, shows a high cytostatic action both "in vivo" and "in vitro".