Synthesis and pharmacological evaluation of new disulfides linked to 1,2,4-triazole bearing urea moiety

The present work involves the synthesis of a series of new disulfides linked to 1,2,4-triazole bearing urea moiety through multistep reaction. The in vitro cytotoxicity of the compounds in three human cancer cell lines (SMMC-7721, A549, Hela) and one normal cell line (L929) was evaluated via CCK-8 assay. Among the synthesized compounds, 3-(4-fluorophenylcarbamoylamino)-5-(n-butyldi-sulfanyl)-1,2,4-triazole ( 7c ) was found to have the greatest antiproliferative activity against SMMC-7721 cells (IC 50 = 1.10 µM) and showed better activity than the lead compound (PX-12, IC 50 = 4.05 µM) and the reference drug (5-FU, IC 50 = 5.62 µM) did. The IC 50 value of 7c in L929 cells was 13.4 times higher than that in the SMMC-7721 cells. Therefore, compound 7c exhibited better potency and specificity compared with PX-12 and 5-FU, and was identified as a promising anticancer lead compound for further development. Graphical Abstract Some target compounds exhibited excellent growth inhibitory effect against various cancer cells.