Carcinostatic action of polycarbonyl compounds and their derivatives. IV. Glyoxal bis (thiosemicarbazone) and derivatives.

series. This compound and many related com pounds are active against Sarcoma 180, particu larly when administered orally in the diet. Glyoxal bis(thiosemicarbazone) has a low toxicity for mice. Some of the more active compounds first synthe sized and tested gave an undesirable side effect of weight loss. However, further synthesis and test ing led to compounds of higher activity, low tox icity, and the elimination of weight loss. Methylglyoxal bis(N4methylthiosemicarbazone), hydroxymethylglyoxal bis(N4methylthiosemicarbazone) and ethoxymethylglyoxal bis(N4methylthiosemicarbazone) are the most effective compounds to date and represent a substantial improvement over the prototype. The chemical evidence and experiments involving variation of the time of initiation of treatment suggest that these 1,2-bis(thiosemicarbazones) may be acting by way of a metal chelation mechanism. Such a mechanism, if valid, points the way to a rationale for definitive synthesis of chemo therapeutic agents.