Aminophosphine and Diphosphine Cyclopentadienyl Iron(II) Compounds: Biological Activity in Breast Cancer Cell Lines
Berenice Sampayo‐Andrade, Maribel Arroyo‐Carranza, Fabiola Lilí Sarmiento‐Salinas, Paola Maycotte, Armando Ramírez‐MonroyABSTRACT
Half‐sandwich iron(II) complexes bearing aminophosphine or diphosphine chelating ligands were systematically evaluated against breast cancer cells to establish structure–activity relationships. Aminophosphine complexes exhibited moderate cytotoxicity toward MCF7 and MDA‐MB‐231 cells (IC 50 = 54 to > 100 μM), compared to cisplatin (43–51 μM), while showing comparable effects on nontumorigenic MCF10A cells (52–85 μM). Morphological analysis, real‐time confluence monitoring, ROS measurements, and cell death assays indicate that these complexes primarily exert cytostatic or proliferation‐modulating effects, characterized by a decrease in proliferation and limited oxidative stress induction. In contrast, the diphosphine complex displayed low micromolar IC 50 values across all tested cell lines, accompanied by increased ROS production, severe morphological changes, rapid loss of confluence, and extensive cell death, consistent with a highly potent but nonselective cytotoxicity mechanism. Systematic experiments confirmed that cytotoxicity arises from the cationic iron(II) complexes rather than counterion identity or degradation products. These results demonstrate that subtle ligand modifications dictate cytotoxic potency, selectivity, and biological mode of action in breast cancer cell lines.