Polyoxomolybdate Bisphosphonate Heterometallic Complexes: Synthesis, Structure, and Activity on a Breast Cancer Cell Line

Ali Saad, Wei Zhu, Guillaume Rousseau, Pierre Mialane, Jérôme Marrot, Mohamed Haouas, Francis Taulelle, Rémi Dessapt, Hélène Serier-Brault, Eric Rivière, Tadahiko Kubo, Eric Oldfield, Anne Dolbecq

Research output: Contribution to journalArticle

Abstract

Six polyoxometalates containing MnII, MnIII, or FeIII as the heteroelement were synthesized in water by treating MoVI 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 MoVI ions linked by the 2-pyridyl analogue of alendronate (AlePy). The complexes Mo4Ale2Mn, Mo4Zol2Mn, Mo4Ale2Fe, Mo4Zol2Fe, Mo4(BPC8NH2)2Fe, and Mo4(BPC9)2Fe contain two dinuclear MoVI cores bound to a central heterometallic ion. The oxidation state of manganese was determined by magnetic measurements. Complexes Mo12(AlePy)4 and Mo12(AlePy)4Pt4 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 MnIII-containing Mo4Zol2Mn (IC50≈1.3 μM). 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.

Original languageEnglish (US)
Pages (from-to)10537-10547
Number of pages11
JournalChemistry - A European Journal
Volume21
Issue number29
DOIs
StatePublished - Jul 1 2015

Keywords

  • NMR spectroscopy
  • bisphosphonates
  • cancer
  • magnetic properties
  • polyoxometalates

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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    Saad, A., Zhu, W., Rousseau, G., Mialane, P., Marrot, J., Haouas, M., Taulelle, F., Dessapt, R., Serier-Brault, H., Rivière, E., Kubo, T., Oldfield, E., & Dolbecq, A. (2015). Polyoxomolybdate Bisphosphonate Heterometallic Complexes: Synthesis, Structure, and Activity on a Breast Cancer Cell Line. Chemistry - A European Journal, 21(29), 10537-10547. https://doi.org/10.1002/chem.201406565