Synthesis of novel 1,2,4-triazoles, triazolothiadiazines and triazolothiadiazoles as potential anticancer agents

•Synthesis of a novel 1,2,4-triazole derivatives.•In vitro anticancer screening for all the synthesized compounds.•Seven of the tested compounds exhibited significant cytotoxicity.•Compound 4c exhibited potent activity against gastric cancer cell line.

A series of new N-substituted-3-mercapto-1,2,4-triazoles (3a,b and 7a–d), triazolo[1,3,4]thiadiazines (5a,b) and triazolo[1,3,4]thiadiazoles (4a–d, 6 and 8a–d) have been synthesized starting from isonicotinic acid hydrazide. The structure of the newly synthesized compounds was confirmed on the basis of their spectral data and elemental analyses. All the compounds were screened for their in vitro anticancer activity against 6 human cancer cell lines and normal fibroblasts. Seven of the tested compounds (3a,b, 4c, 5a and 8b–d) exhibited significant cytotoxicity against most cell lines. Among these derivatives compound 4c exhibited equivalent cytotoxic effect to the standard CHS 828 against gastric cancer cell line (IC50 = 25 nM). Normal fibroblast cells (WI38) were affected to a much lesser extent (IC50 > 10,000 nM).

Graphical abstractA series of new 3-mercapto-1,2,4-triazoles, triazolo[1,3,4]thiadiazines and triazolo[1,3,4]thiadiazoles were synthesized. The compounds were screened for their in vitro anticancer activity. Compound 4c exhibited potent cytotoxicity against gastric cancer cell line.Figure optionsDownload full-size imageDownload as PowerPoint slide