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Polyoxomolybdate Bisphosphonate Heterometallic Complexes: Synthesis, Structure, and Activity on a Breast Cancer Cell Line
Author(s) -
Saad Ali,
Zhu Wei,
Rousseau Guillaume,
Mialane Pierre,
Marrot Jérôme,
Haouas Mohamed,
Taulelle Francis,
Dessapt Rémi,
SerierBrault Hélène,
Rivière Eric,
Kubo Tadahiko,
Oldfield Eric,
Dolbecq Anne
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201406565
Subject(s) - bisphosphonate , chemistry , polyoxometalate , electron paramagnetic resonance , manganese , ligand (biochemistry) , stereochemistry , crystallography , nuclear chemistry , organic chemistry , biochemistry , medicine , receptor , osteoporosis , nuclear magnetic resonance , endocrinology , catalysis , physics
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 (BPC 9 ), an aminoalkyl bisphosphonate (BPC 8 NH 2 )) 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 (BPC 8 NH 2 ) 2 Fe, and Mo 4 (BPC 9 ) 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 (IC 50 ≈1.3 μ M ). 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.