Synthesis of novel 1,2,4-triazoles and triazolo-thiadiazines as anticancer agents

A new series of 7-arylazo-5 H-3-(trifluoromethyl)-6-methyl-1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazines was prepared by reaction of 4-amino-3-trifluoromethyl-5-mercapto-1,2,4-triazoles with N-aryl-2-oxo-propane hydrazonoyl chloride in dioxane under reflux in the presence of triethylamine. Furthermore, Schiff bases of 4-amino-5-mercapto-1,2,4-triazole derivatives were reacted with a variety of hydrazonoyl chlorides and gave the respective hydrazonothioates. In addition, the novel bis-(1,2,4-triazole-3-thione) was reacted with the appropriate hydrazonoyl chloride in dioxane under reflux in the presence of triethylamine to give the corresponding bis-(1,2,4-triazolethiohydrazonoate). The structures of the new compounds were established based on elemental and spectral data. The mechanism of the studied reaction was also discussed. Moreover, some of the new products were screened for their anticancer activity and the results obtained are promising and indicate that compounds 4a and 4i are the most active inhibitors against HEPG-2 and compounds 4a and 13b are active against HCT cell lines.