Cd(II) and Pb(II) complexes of the polyether ionophorous antibiotic salinomycin

<p>Abstract</p> <p>Background</p> <p>The natural polyether ionophorous antibiotics are used for the treatment of coccidiosis in poultry and ruminants. They are effective agents against infections caused by Gram-positive microorganisms. On the other hand, it was found that some of these compounds selectively bind lead(II) ions in <it>in vivo </it>experiments, despite so far no Pb(II)-containing compounds of defined composition have been isolated and characterized. To assess the potential of polyether ionophores as possible antidotes in the agriculture, a detailed study on their <it>in vitro </it>complexation with toxic metal ions is required. In the present paper we report for the first time the preparation and the structure elucidation of salinomycin complexes with ions of cadmium(II) and lead(II).</p> <p>Results</p> <p>New metal(II) complexes of the polyether ionophorous antibiotic salinomycin with Cd(II) and Pb(II) ions were prepared and structurally characterized by IR, FAB-MS and NMR techniques. The spectroscopic information and elemental analysis data reveal that sodium salinomycin (SalNa) undergoes a reaction with heavy metal(II) ions to form [Cd(Sal)₂(H₂O)₂] (<b>1</b>) and [Pb(Sal)(NO₃)] (<b>2</b>), respectively. Abstraction of sodium ions from the cavity of the antibiotic is occurring during the complexation reaction. Salinomycin coordinates with cadmium(II) ions as a bidentate monoanionic ligand through the deprotonated carboxylic moiety and one of the hydroxyl groups to yield <b>1</b>. Two salinomycin anions occupy the equatorial plane of the Cd(II) center, while two water molecules take the axial positions of the inner coordination sphere of the metal(II) cation. Complex <b>2 </b>consists of monoanionic salinomycin acting in polydentate coordination mode in a molar ratio of 1: 1 to the metal ion with one nitrate ion for charge compensation.</p> <p>Conclusion</p> <p>The formation of the salinomycin heavy metal(II) complexes indicates a possible antidote activity of the ligand in case of chronic/acute intoxications likely to occur in the stock farming.</p

Sterically stabilized liposomes as a platform for salinomycin metal coordination compounds

Sterically stabilized DPPC:CHOL:DSPE-PEG-2000 liposomal formulations of the lipophilic complexes of salinomycin with Na(I), K(I), Mn(II), Co(II), and Ni(II) ions were prepared by film-hydration method at different drug-to-DPPC molar ratios. For the K(I) and Na(I) complexes, optimal loading was established at a drug-to-DPPC molar ratio of 0.5:1, whereas for the Me(II) complexes, it was encountered at 0.1:1. DLS revealed uniform LUV populations (130-160 nm) with monomodal size distribution, further corroborated by AFM. Free and entrapped salinomycinates exhibited cytotoxicity in three human tumor cell lines, whereby the liposomal agents were superior vs. free complexes. DNA-fragmentation and flow cytometric assays showed that the cytotoxicity of free and liposomal salinomycinates is mediated by the induction of apoptosis and G1 arrest. The ability of the carriers to retain the bio-activity of the entrapped cargo gives us reason to conclude that the presented DPPC:CHOL:DSPE-PEG-2000 liposomes are suitable platforms for the salinomycin complexes, needing further evaluation and optimization