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首页> 外文期刊>Chemistry: A European journal >Polyoxomolybdate Bisphosphonate Heterometallic Complexes: Synthesis, Structure, and Activity on a Breast Cancer Cell Line
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Polyoxomolybdate Bisphosphonate Heterometallic Complexes: Synthesis, Structure, and Activity on a Breast Cancer Cell Line

机译：聚氧钼酸双膦酸盐异金属配合物：乳腺癌细胞系的合成，结构和活性。

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摘要

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.
机译：通过使用具有生物活性的双膦酸盐（阿仑膦酸盐（Ale），唑来膦酸盐（Zol），正烷基双膦酸盐（BPC9））处理Mo-VI前体，在水中合成了六种含有Mn-II，Mn-III或Fe-III作为杂元素的多金属氧酸盐。 ），在其他金属离子存在下的双膦酸氨基烷基酯（BPC8NH2））。 Pt络合物是由聚氧钼酸双膦酸酯前体合成的，其中Mo-VI离子通过阿仑膦酸酯（AlePy）的2-吡啶基类似物连接。配合物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和Mo-4（BPC9）（2）Fe包含两个与中心杂金属离子键合的双核Mo-VI核。锰的氧化态通过磁性测量来确定。通过固态NMR光谱研究了配合物Mo-12（AlePy）（4）和Mo-12（AlePy）（4）Pt-4，并在固态下研究了光致变色性质。两种方法均证实了Pt的络合。确定了针对人乳腺癌细胞系MCF-7的活性，最有效的化合物是含Mn-III的Mo（4）Zol（2）Mn（IC50约为1.3M）。与用含钒的多金属氧酸盐双膦酸盐获得的结果不同，通过加入香叶基香叶醇可以挽救细胞生长的抑制作用，这逆转了双膦酸盐对类异戊二烯生物合成/蛋白质异戊二烯化的影响。结果表明，杂金属元素和双膦酸酯配体在最具活性的化合物的作用机理中均起着重要作用。

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