title: Polyoxomolybdate Bisphosphonate Heterometallic Complexes: Synthesis, Structure, and Activity on a Breast Cancer Cell Line.
abstract: 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 (BPC8 NH2 )) 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 Mo4 Ale2 Mn, Mo4 Zol2 Mn, Mo4 Ale2 Fe, Mo4 Zol2 Fe, Mo4 (BPC8 NH2 )2 Fe, and Mo4 (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 Mo12 (AlePy)4 and Mo12 (AlePy)4 Pt4 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 Mo4 Zol2 Mn (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.
authors.affiliation: Institut Lavoisier de Versailles, UMR 8180, Université de Versailles St-Quentin en Yvelines, 45 Avenue des Etats-Unis, 78035 Versailles cedex (France).
authors.forename: Ali
authors.initials: A
authors.lastname: Saad
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 6180 (USA).
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Institut Lavoisier de Versailles, UMR 8180, Université de Versailles St-Quentin en Yvelines, 45 Avenue des Etats-Unis, 78035 Versailles cedex (France).
authors.forename: Guillaume
authors.initials: G
authors.lastname: Rousseau
authors.affiliation: Institut Lavoisier de Versailles, UMR 8180, Université de Versailles St-Quentin en Yvelines, 45 Avenue des Etats-Unis, 78035 Versailles cedex (France).
authors.forename: Pierre
authors.initials: P
authors.lastname: Mialane
authors.affiliation: Institut Lavoisier de Versailles, UMR 8180, Université de Versailles St-Quentin en Yvelines, 45 Avenue des Etats-Unis, 78035 Versailles cedex (France).
authors.forename: Jérôme
authors.initials: J
authors.lastname: Marrot
authors.affiliation: Institut Lavoisier de Versailles, UMR 8180, Université de Versailles St-Quentin en Yvelines, 45 Avenue des Etats-Unis, 78035 Versailles cedex (France).
authors.forename: Mohamed
authors.initials: M
authors.lastname: Haouas
authors.affiliation: Institut Lavoisier de Versailles, UMR 8180, Université de Versailles St-Quentin en Yvelines, 45 Avenue des Etats-Unis, 78035 Versailles cedex (France).
authors.forename: Francis
authors.initials: F
authors.lastname: Taulelle
authors.affiliation: Institut des Matériaux Jean Rouxel, Université de Nantes, CNRS, 2 Rue de la Houssinière, BP 32229, 44322 Nantes cedex (France).
authors.forename: Rémi
authors.initials: R
authors.lastname: Dessapt
authors.affiliation: Institut des Matériaux Jean Rouxel, Université de Nantes, CNRS, 2 Rue de la Houssinière, BP 32229, 44322 Nantes cedex (France).
authors.forename: Hélène
authors.initials: H
authors.lastname: Serier-Brault
authors.affiliation: Institut de Chimie Moléculaire et des Matériaux d'Orsay, UMR 8182, Université Paris-Sud, 91405 Orsay cedex (France).
authors.forename: Eric
authors.initials: E
authors.lastname: Rivière
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Miniami-ku, Hiroshima 734-8551 (Japan).
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Kubo
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 6180 (USA). eo@chad.scs.uiuc.edu.
authors.forename: Eric
authors.initials: E
authors.lastname: Oldfield
authors.affiliation: Institut Lavoisier de Versailles, UMR 8180, Université de Versailles St-Quentin en Yvelines, 45 Avenue des Etats-Unis, 78035 Versailles cedex (France). anne.dolbecq@uvsq.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Dolbecq
mesh_terms: D001943:Breast Neoplasms; D002460:Cell Line; D018360:Crystallography, X-Ray; D004164:Diphosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D007501:Iron / Q000737:chemistry; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008345:Manganese / Q000737:chemistry; D008982:Molybdenum / Q000737:chemistry* / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D008024:Ligands; D009942:Organometallic Compounds; D008345:Manganese; D000077211:Zoledronic Acid; D008982:Molybdenum; D007501:Iron
keywords: NMR spectroscopy; bisphosphonates; cancer; magnetic properties; polyoxometalates