Observations on the antileukemic activity of pyridine-2-carboxaldehyde thiosemicarbazone and thiocarbohydrazone.

The investigation of the biological activity of thiosemicarbazones had as its origin Domagk's attempt to establish a relationship between the structure and antituberculous activity of a series of sulfathiadiazoles which were prepared by cyclizing the corresponding thiosemicarbazones (4). The end product, the thiadiazoles, proved uninteresting, but the intermediate thiosemicarbazones, which were tested by Behnisch and his group in Germany, were reported in 1946 to be strongly tuberculostatic in vivo (1, 4). Interest in compounds of this type was stimulated by the report of Hamre and her group at the Squibb Institute for Medical Research that certain of the aromatic aldehyde thiosemicarbazones possessed in vivo activity against vaccinia virus--both in embryonated eggs and in mice (3, 5, 6). The antivaccinial activity of this class of compounds in mice has been confirmed and extended by R. L. Thompson and his co-workers (8, 9, 10, 11) and in this laboratory. ~ Compounds capable of inhibiting virus multiplication, which presumably involves synthesis of nucleoprotein, are of interest as candidate anticancer agents. Thiosemicarbazones have been tested, therefore, for activity against several solid tumors and leukemias in mice. Metaand paranitrobenzaldehyde thiosemicarbazones were found to have weak but consistent activity against Adenocarcinoma 755, restricting tumor growth to 40-50 per cent of that in untreated controls at levels that did not result in weight loss or death of treated animals? Thiosemicarbazones appear to be