Anticancer activity of the new manganese(II), iron(II), nickel(II), copper(II), and zinc(II) complexes based on 1,2,4-triazoline-3-thione derivative.

In this study, we report the anticancer evaluation, synthesis, and characterization of a novel organic ligand, 4-butyl-5-((1-methyl-1H-pyrrol-2-yl)methyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione and its five metal complexes based on Mn(II), Fe(II), Ni(II), Cu(II), and Zn(II) ions. All compounds were analyzed using elemental analysis, NMR and FTIR spectroscopies, magnetic measurements, ESR, and thermogravimetric analysis. Their antioxidant properties were evaluated using the ABTS and DPPH assays, and the anticancer activity was studied in silico via molecular docking and in vitro against a panel of cancer cell lines. Notably, the Fe(II), Ni(II), and Cu(II) complexes exhibited potent anticancer activity, with IC50 values of 40.66, 45.95, and 26.51 µM against MDA-MB-231 cells. Their mechanism of action was further investigated through gene expression analysis, cell cycle analysis, apoptosis detection, thiol level evaluation, and DNA damage assessment. The results revealed that Ni(II) and Cu(II) complexes are significantly cytotoxic, while the Fe(II) complex acts as a potent cytostatic agent. Importantly, all compounds demonstrated lower activity toward normal cells than the tested cancer cells.