Synthesis and in vivo antitumor activity of new heterocyclic derivatives of the 1,3,4-thiadiazolium-2-aminide class

Four new mesoionic compounds derivates of 4-phenyl-5-(4-X-cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine chlorides were synthesized and their antitumor activities against Ehrlich carcinoma and Sarcoma 180 (S180) were evaluated. In the schedule assayed, the derivates where X = OH and X = NO2 injected i.p. in mice at a total dose level of 10 and 30 mg/kg respectively caused a significant inhibition of ascitic S180 growth, and at a dose of 25 mg/kg inhibited the growth of Ehrlich carcinoma. The derivates where X = H and X = OCH3 did not show activity. There are no significant changes of hematopoietic parameters of the derivatives in this treatment. These data suggest that the presence of more polar substituents, NO2 and OH, strongly increases the antitumor activity of this class of compounds.