Saad, A., Zhu, W., Rousseau, G., Mialane, P., Marrot, J., Haouas, M., Taulelle, F., Dessapt, R., Serier-Brault, H., Riviere, E., Kubo, T., Oldfield, E. & Dolbecq, A. (2015) Polyoxomolybdate Bisphosphonate Heterometallic Complexes: Synthesis, Structure, and Activity on a Breast Cancer Cell Line. Chem.-Eur. J. 21 10537–10547.
Added by: Laurent Cournède (2016-03-10 18:36:41)
|Type de référence: Article
Numéro d'identification (ISBN etc.): 0947-6539
Clé BibTeX: Saad2015
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Mots-clés: biological-activity, bisphosphonates, cancer, density-functional theory, electron-paramagnetic-resonance, field, ligands, lipophilic bisphosphonates, Magnetic properties, mn-ii ion, NMR spectroscopy, photochromic properties, polyoxometalates, solid-state, x-ray
Créateurs: Dessapt, Dolbecq, Haouas, Kubo, Marrot, Mialane, Oldfield, Riviere, Rousseau, Saad, Serier-Brault, Taulelle, Zhu
Collection: Chem.-Eur. J.
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Six polyoxometalates containing Mn-II, Mn-III, or Fe-III as the heteroelement were synthesized in water by treating Mo-VI precursors with biologically active bisphosphonates (alendronate (Ale), zoledronate (Zol), an n-alkyl bisphosphonate (BPC9), an aminoalkyl bisphosphonate (BPC8NH2)) in the presence of additional metal ions. The Pt complex was synthesized from a polyoxomolybdate bisphosphonate precursor with Mo-VI ions linked by the 2-pyridyl analogue of alendronate (AlePy). The complexes Mo(4)Ale(2)Mn, Mo(4)Zol(2)Mn, Mo(4)Ale(2)Fe, Mo(4)Zol(2)Fe, Mo-4(BPC8NH2)(2)Fe, and Mo-4(BPC9)(2)Fe contain two dinuclear Mo-VI cores bound to a central heterometallic ion. The oxidation state of manganese was determined by magnetic measurements. Complexes Mo-12(AlePy)(4) and Mo-12(AlePy)(4)Pt-4 were studied by solid-state NMR spectroscopy and the photochromic properties were investigated in the solid state; both methods confirmed the complexation of Pt. Activity against the human breast adenocarcinoma cell line MCF-7 was determined and the most potent compound was Mn-III-containing Mo(4)Zol(2)Mn (IC50 approximate to 1.3M). Unlike results obtained with vanadium-containing polyoxometalate bisphosphonates, cell growth inhibition was rescued by the addition of geranylgeraniol, which reverses the effects of bisphosphonates on isoprenoid biosynthesis/protein prenylation. The results indicate an important role for both the heterometallic element and the bisphosphonate ligand in the mechanism of action of the most active compounds.
Added by: Laurent Cournède