Biochemical Characterization of Propylglyoxal Bis(guanylhydrazone). Facile Synthesis of Monoalkylglyoxal Bis(guanylhydrazones)

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Abstract
Propylglyoxal Bis(guanylhydrazone). Ethylglyoxal Bis(guanylhydrazone), Adenosylmethionine Decarboxylase Inhibition. Tumor Cells, Cellular Uptake Propylglyoxal bis(guanylhydrazone) sulfate, a novel analog of the well-known antileukemic drug methylglyoxal bis(guanylhydrazone), has been prepared from 2,2-dibromopentanal, and the compound has been characterized biochemically. Although it is a powerful inhibitor of S-adenosylmethionine decarboxylase, its Ki, value (0.2 μᴍ) is considerably higher than that of ethylglyoxal bis(guanylhydrazone) (0.06 μᴍ). The compound is only poorly taken up by tumor cells, and its accumulation is not stimulated by a prior exposure of the tumor cells to di-fluoromethylornithine, a compound that causes polyamine depletion. Thus, the uptake charac­ teristics of the compound are similar to those of ethylglyoxal bis(guanylhydrazone), but in striking contrast to those of methylglyoxal and glyoxal bis(guanylhydrazones). Since the configuration of the double bonds in glyoxal, methylglyoxal and propylglyoxal bis(guanylhydrazones) has been shown to be identical, the different uptake characteristics are probably only due to differences in side chain size and/or hydrophobicity.