Anticancer Activity of Bisthiosemicarbazones of Methylglyoxal1

We have been interested for some time in thiosemicarbazide derivatives of periodate-oxidized polysaccharides many of which show considerable activity against Sarcoma 180 (S-180) in the mouse (2). The antitumor activity and toxicity of these deriva tives are completely reversed if pyridoxine (B6) is administered at the same time. We were led to investigate glyoxal and methylglyoxal bisthiosemicarbazones as probable degradation products of the polymers. A number of reports (1, 5, 7) have appeared on the antitumor activity of bisthiosemicarbazones of a-ketoaldehydes; activity appeared to be confined to compounds in which the thiosemi carbazide residues carried a substituent not larger than ethyl on the JV4-position. The present investigation has been directed to the study of the effect of varying the AT4-substituents R1 and R2