Synthesis and Screening of New [1,3,4]Oxadiazole, [1,2,4]Triazole, and [1,2,4]Triazolo[4,3-][1,2,4]triazole Derivatives as Potential Antitumor Agents on the Colon Carcinoma Cell Line (HCT-116).

New derivatives of [1,3,4]oxadiazole-2-thione and triazole-3-thione were synthesized through the cyclocondensation of dicarbonyl ester with phenyl hydrazine followed by hydrazinolysis to give the corresponding hydrazide, which reacted with carbon disulfide or ammonium thiocyanate to afford [1,3,4]oxadiazole or triazole-3-thione , respectively. Hydrazinolysis of compound gave [1,2,4]triazole-3-thiol which was treated with different aromatic aldehydes to obtain . Mannich bases were obtained from the reaction of Schiff bases with morpholine and formaldehyde. Moreover, treatment of triazole-3-thione with hydrazine was followed by cyclocondensation with diethyl oxalate, chloroacetic acid, or formic acid to give the corresponding [1,2,4]triazine-3,4-dione , [1,2,4]triazin-4-one or [1,2,4]triazolo[4,3-b][1,2,4] triazole respectively. Screening of some chosen synthesized compounds against the human colon carcinoma cancer cell lines showed that the compound [1,2,4]triazole-3-thiol exhibiting cytotoxic activity was roughly equivalent to standard Vinblastine, while compounds , , , , and exhibited moderate cytotoxic activity.