TY - JOUR
T1 - Polyoxomolybdate Bisphosphonate Heterometallic Complexes
T2 - Synthesis, Structure, and Activity on a Breast Cancer Cell Line
AU - Saad, Ali
AU - Zhu, Wei
AU - Rousseau, Guillaume
AU - Mialane, Pierre
AU - Marrot, Jérôme
AU - Haouas, Mohamed
AU - Taulelle, Francis
AU - Dessapt, Rémi
AU - Serier-Brault, Hélène
AU - Rivière, Eric
AU - Kubo, Tadahiko
AU - Oldfield, Eric
AU - Dolbecq, Anne
N1 - Publisher Copyright:
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - 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.
AB - 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.
KW - NMR spectroscopy
KW - bisphosphonates
KW - cancer
KW - magnetic properties
KW - polyoxometalates
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U2 - 10.1002/chem.201406565
DO - 10.1002/chem.201406565
M3 - Article
C2 - 26076183
AN - SCOPUS:84934270083
SN - 0947-6539
VL - 21
SP - 10537
EP - 10547
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 29
ER -