Synthesis and Cytotoxicity Evaluation of N-(5-mercapto-4H-1,2,4-triazol3-yl)-2-phenylacetamide Derivatives as Apoptosis Inducers with Potential Anticancer Effects

Discovery of new anticancer drugs is one of the urgent issues in the medicinal chemistry researches. Incidence of severe side effects and acquired resistance to the current medications are the logical reasons for the development of novel antineoplastic agents.

Herein, a new series of 4H-1,2,4-triazole derivatives was synthesized and subsequently their cytotoxicity was assessed using dimethylthiazol diphenyltetrazolium bromide assay. Furthermore, activity of caspase 3, mitochondrial membrane potential (MMP), and generation of reactive oxygen species (ROS) were investigated. All synthesized derivatives (3a–3o) were tested against Hela (cervical cancer), A549 (lung carcinoma), and U87 (glioblastoma), and the obtained data were compared with doxorubicin.

Among the chlorinated derivatives, compound 3c with para positioning of the chlorine on the phenyl residue possessed higher cytotoxicity (IC50 = s3.2 ± 0.6 μM) than compounds 3a and 3b, which positioned chlorine at ortho and meta position, respectively. Chlorine as electron-withdrawing moiety caused enhancement in cytotoxicity.

Fortunately, most of the tested compounds showed remarkable cytotoxic activity toward applied cells, especially Hela. Activation of caspase 3, MMP reduction, and ROS generation were also observed for the studied compounds.