Iron(III), ruthenium(III), and cobalt(III) complexes bearing diimines and amino acids as potent anticancer agents: synthesis, DFT, molecular docking, and biological activity

A series of water-soluble mixed-ligands iron(III) (1?3), ruthenium(III) (4, 5), and cobalt(III) (6?8) complexes bearing amino acids and heterocyclic diimine ligands, with the general formula [M(AA)2(Nsingle bondN)]Cl, where (M = Fe, Ru, and Co); (AA = L-leucine, leu; L-glutamic acid, glu); (N-N = 2,2?-bipyridine (bipy) and 1,10-phenanthroline (phen)) were synthesized. The complexes were characterized using elemental analysis, molar conductivity, IR, UV?Vis spectroscopy, and fluorescence spectroscopy. According to the analytical data and structural analysis using density functional theory (DFT) of the complexes, the mixed ligands formed a distorted octahedral geometry around the metal center. The in vitro antiproliferative activities of the complexes were evaluated against three human breast cancer cell lines (BT549, MCF-7, and T47D). Leucine-based iron(III), ruthenium(III), and cobalt(III) complexes containing 1,10-phenanthroline (2, 5, and 7, respectively) exhibited higher cytotoxicity against all studied breast cancer cell lines than the corresponding bipyridine-based complexes. Moreover, these complexes showed cancer selectivity against the non-malignant MCF10A cells. Among the studied complexes, complex 2, containing leucine and 1,10-phenanthroline moieties, exhibited the most potent cytotoxicity against the tested cancer cells, showing activity comparable to that of cisplatin against BT549 and MCF-7 breast cancer cell lines (IC50 = 23.4 ?M and 20.4 ?M, vs 34.2 ?M and 31.3 ?M respectively). Consequently, complex 2 was selected for molecular docking studies to investigate its interactions and inhibition of receptor tyrosine kinases (EGFR and HER2) and estrogen receptor alpha (ER?).