Anticancer diiron aminocarbyne complexes with labile N-donor ligands
Language English Country France Media print-electronic
Document type Journal Article
PubMed
39862748
DOI
10.1016/j.ejmech.2025.117304
PII: S0223-5234(25)00069-8
Knihovny.cz E-resources
- Keywords
- Bioorganometallic chemistry, Cellular effects, Diiron complexes, In vitro cytotoxicity, Labile ligand,
- MeSH
- Amines chemistry pharmacology MeSH
- Coordination Complexes chemistry pharmacology chemical synthesis MeSH
- Humans MeSH
- Ligands MeSH
- Molecular Structure MeSH
- Cell Line, Tumor MeSH
- Cell Proliferation * drug effects MeSH
- Antineoplastic Agents * pharmacology chemistry chemical synthesis MeSH
- Drug Screening Assays, Antitumor * MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Iron chemistry MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Amines MeSH
- Coordination Complexes MeSH
- Ligands MeSH
- Antineoplastic Agents * MeSH
- Iron MeSH
The novel diiron amine complexes [Fe2Cp2(CO)(NH2R')(μ-CO){μ-CN(Me)(Cy)}]CF3SO3 [R' = H, 3; Cy, 4; CH2CH2NH2, 5; CH2CH2NMe2, 6; CH2CH2(4-C6H4OMe), 7; CH2CH2(4-C6H4OH), 8; Cp = η5-C5H5, Cy = C6H11 = cyclohexyl] were synthesized in 49-92 % yields from [Fe2Cp2(CO)2(μ-CO){μ-CN(Me)(Cy)}]CF3SO3, 1a, using a straightforward two-step procedure. They were characterized by IR and multinuclear NMR spectroscopy, and the structure of 7 was confirmed through X-ray diffraction analysis. Complexes 3-8 and the acetonitrile adducts [Fe2Cp2(CO)(NCMe)(μ-CO){μ-CN(Me)(R)}]CF3SO3 (R = Cy, 2a; Me, 2b; Xyl = 2,6-C6H3Me2, 2c) were assessed for their water solubility, octanol-water partition coefficient and stability in physiological-like solutions. The in vitro antiproliferative activity of 2a-c and 3-8 was tested on seven human cancer cell lines (A2780, A2780R, PC3, A549, MCF7, HOS and HT-29), while the selectivity was evaluated using normal MRC-5 cells. Overall, the complexes exhibited variable cytotoxicity, with IC50 values reaching the low micromolar range for 3, 7 and 8 in A2780 and A2780R cells, along with significant selectivity. Targeted experiments covered cell cycle modification, induction of cell death, mitochondrial membrane potential, ROS production and interaction with DNA and bovine serum albumin (BSA) as a model protein. The interaction of 3 with BSA was further investigated through computational studies. Results showed a negligible increase in intracellular ROS levels (except for 2b) and insignificant changes in mitochondrial membrane potential.
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