Bimetallic Anilinopyridinate ruthenium(II,III) complexes: Synthesis, characterisation, and in vitro selective cytotoxicity towards MCF-7 breast cancer cells

Cancer is the second leading cause of death worldwide. Treatment options such as conventional chemotherapeutic agents often have significant shortcomings. To address such treatment modalities, ruthenium(III) prodrugs offer promise as anticancer agents with superior efficacy. Fuelled by this ongoing research, this work evaluates lantern-type diruthenium(II,III) complexes against ER + ve MCF-7 and triple-negative MDA-MB-231 breast cancer cells. Stoichiometric reactions of unsymmetrical N,N'-anilinopyridinate (R-ap) ligands with [Ru2(O2CCH3)4Cl] yielded five mono-substituted anilinopyridinate trisacetatochlorodiruthenium(II,III) complexes, ([Ru2(O2CCH3)3(R-ap)Cl]) (C1 - C5; R = H, 2-CH3, 4-CH3, 2-F, and 4-F) in moderate yields. All ligands and complexes are fully characterised using spectroscopic and analytical techniques, with assignments matching literature data. Crystal structures of C1, C3 and C5 show lantern-type structures in triclinic space groups. Complexes maintain their paramagneticity with magnetic moments 3.50 μB (C1), 3.64 μB (C3), 3.85 μB (C4) and 4.10 μB (C5), respectively, indicative of three unpaired electrons in the π* and δ* orbitals. Free R-ap ligands exhibited negligible cytotoxicity against human breast MCF-7 and MDA-MB-231 cancers, while coordination to the Ru25+ cores enhanced their solubility and efficacy over the precursor [Ru2(O2CCH3)4Cl]. C3 and C5 show promising cytotoxicity against MCF-7 cells (IC50: 39.0 μM and 49.1 μM), outperforming cisplatin in selectivity for MCF-7 cancer cells. C3 induces DNA damage, the cell cycle (p53), and apoptosis (caspase 9 and poly (ADP-ribose) polymerase protein (PARP)). Altogether, these results suggest that [Ru2(O2CCH3)3(R-ap)Cl] complexes show promising anticancer properties against MCF-7 human breast cancer cells. Additionally, the possible mechanisms of action of [Ru2(O2CCH3)3(R-ap)Cl] complexes were highlighted.