Design, Synthesis and Cytotoxicity Evaluation of N-(5-Benzylthio)-4H-1,2,4-Triazol-3-YL)-4-Fluorobenzamide Derivatives as Potential Anticancer Agents

Abstract

Despite advances in anticancer drug development and discovery, the survival of patients is so poor. A deep need for discovery of novel anticancer drugs is among priority issues in medicinal chemistry now. A new series of 1,2,4-triazole derivatives were designed and synthesized by means of bioisosteric replacement. In vitro cytotoxicity evaluation was carried out with respect to PC3 (prostate carcinoma), HT29 (colorectal cancer) and SKNMC (neuroblastoma) cell lines using MTT assay, and the obtained results were compared to imatinib as a reference drug. Spectroscopic methods including 1H NMR, IR, and MS were used for characterization of the synthesized compounds. Generally, none of the tested compounds showed superior activity in comparison to imatinib against PC3 and SKNMC cell lines. However, compound 3b (IC₅₀ = 3.69 ± 0.9 μM) and 3e(IC₅₀ = 15.31 ± 2.1 μM) exhibited higher activity than imatinib (18.1 ± 2.6) against HT29 cells. Some of the obtained 1,2,4-triazole derivatives can be proposed as potential anticancer agents – in particular, against colorectal cancer – but further structural modifications and experimental tests are needed to increase the anticancer activity.