Biochemical and chemical characterization of trifluoromethylglyoxal bis(guanylhydrazone), a close analog of the antileukemic drug mitoguazone.
In order to study the structure-activity relationships of bis(guanylhydrazone) type polyamine antimetabolites, trifluoromethylglyoxal bis(guanylhydrazone) (CF3-GBG), a close analog of the antileukemic drug methylglyoxal bis(guanylhydrazone) (mitoguazone, MGBG) was synthesized according to a novel modification of previous methods, yielding single crystals. Single-crystal X-ray crystallography revealed the presence of an isomer different from the one detected in the case of MGBG and all other bis(guanylhydrazones) so far studied. In contrast to MGBG, CF3-GBG was shown to be a very weak inhibitor of yeast adenosylmethionine decarboxylase, being thus devoid of value as a polyamine antimetabolite. In addition, the compound did not have antiproliferative activity against mouse L1210 leukemia cells in vitro. As long as analogous isomers of the two compounds are not available, no conclusions can be drawn about the reasons lying behind the drastical differences between their biological properties.
Elo
H
H
Department of Chemistry, University of Helsinki, Finland.
Mutikainen
I
I
D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D008935:Mitoguazone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008958:Models, Molecular; D008968:Molecular Conformation; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D014961:X-Ray Diffraction
D000970:Antineoplastic Agents; C058593:trifluoromethylglyoxal-bis(guanylhydrazone); D012437:Adenosylmethionine Decarboxylase; D008935:Mitoguazone