Anticancer Activity of Polyoxometalate-Bisphosphonate Complexes: Synthesis, Characterization, In Vitro and In Vivo Results
2017
We synthesized a series of polyoxometalate-bisphosphonate complexes containing MoVIO6 octahedra, zoledronate, or an N-alkyl (n-C6 or n-C8) zoledronate analogue, and in two cases, Mn as a heterometal. Mo6L2 (L = Zol, ZolC6, ZolC8) and Mo4L2Mn (L = Zol, ZolC8) were characterized by using single-crystal X-ray crystallography and/or IR spectroscopy, elemental and energy dispersive X-ray analysis and 31P NMR. We found promising activity against human nonsmall cell lung cancer (NCI-H460) cells with IC50 values for growth inhibition of ∼5 μM per bisphosphonate ligand. The effects of bisphosphonate complexation on IC50 decreased with increasing bisphosphonate chain length: C0 ≈ 6.1×, C6 ≈ 3.4×, and C8 ≈ 1.1×. We then determined the activity of one of the most potent compounds in the series, Mo4Zol2Mn(III), against SK-ES-1 sarcoma cells in a mouse xenograft system finding a ∼5× decrease in tumor volume than found with the parent compound zoledronate at the same compound dosing (5 μg/mouse). Overall, the results ar...
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