Five new complexes with deferiprone and N,N-donor ligands: evaluation of cytotoxicity against breast cancer MCF-7 cell line and HSA-binding determination

In this study, five new complexes containing deferiprone (dfp) and N,N-donor ligands [bipyridine (bpy), 1,10-phenanthroline (phen) and ethylenediamine (en)] were synthesized: [Fe(dfp)(2)(bpy)](PF6) (1), [Fe(dfp)(2)(phen)](PF6) (2), [Cu-2(dfp)(2)(bpy)(2)](PF6)(2)(3), [Ga(dfp)(2)(bpy)](PF6) (4), and [Fe(dfp)(2)(en)](PF6) (5). Characterization of these complexes was carried out through elemental analysis and FT-IR, and single-crystal X-ray crystallography was used to determine their structures. Whilst the polyhedron has a distorted octahedral geometry in1,2,4, and5, it adopts a distorted square-pyramidal geometry in3. Interaction of these compounds with human serum albumin (HSA) has been investigated through electronic absorption and fluorescence titration techniques. Emission quenching was performed separately for each complex at three different temperatures and thermodynamic parameters were calculated using binding constants to better understand the power of different binding forces with the HSA. Results demonstrated that compounds interact strongly with the HSA with a static quenching mechanism. Our evaluation of the cytotoxicity of complexes against the breast cancer MCF-7 cell line showed that complex2presents a better cytotoxicity than the standardcis-Pt. Finally, using the AutoDock 4.2 program, simulations to analyze the mechanism of complex-HSA interactions and their binding mode were carried out. Results showed that the best binding mode is located in subdomain IB for1,2, and4, in I/II for3, and in IA/IIA for5. Communicated by Ramaswamy H. Sarma