Carcinostatic action of polycarbonyl compounds and their derivatives. II. Glyoxal bis (guanylhydrazone) and derivatives.

The authors have previously investigated the carcinostatic effect of simple hydrazine deriva tives. In early work (6, 7) acetic hydrazide and some methylated derivatives of formic hydrazide were found to have an inhibitory effect on mouse Adenocarcinoma 755. A number of substituted hydrazines and related compounds were also evaluated on myeloid mouse leukemia C1498 (8). The development of hydrazine derivatives of high antibacterial activity (1, 5) and the detection of antiviral activities in this class of compounds (3) gave substance to the feeling that potent antitumor activities might be found among suitably structured hydrazine derivatives. The report of Brockman et al. (2) on the antileukemic effect of pyridine-2-carboxaldehyde thiosemicarbazone fur ther confirmed this thesis. Analysis of the published results and of exten sive unpublished data accrued in this laboratory indicated the desirability of synthesizing and testing diand polyfunctional hydrazones, so con stituted as to have improved chemical stability and more favorable structural attributes. Conse quently, a number of compounds were synthe sized. Included in this series were a number of bis(guanylhydrazones) of simple 1,2-dicarbonyl compounds. These compounds were tested on lymphocytic Leukemia L1210, Sarcoma 180, and Neuroblastoma C-1300. Intensive studies were made of the prototype compound, glyoxal bis(guanylhydiazone) :