- AMER CHEMICAL SOC
We synthesized a series of polyoxometalatebisphosphonate complexes containing Mov106 octahedra, zoledronate, or an N-alkyl (n-C-6 or n-C-8) zoledronate analogue, and in two cases, Mn as a heterometal. Mo6L2 (L = Zol, ZolC(6), ZolC(8)) and MO4L2Mn = Zol, ZolC(8)) were characterized by using single-crystal X-ray crystallography and/or IR spectroscopy, elemental and energy dispersive X-ray analysis and P-31 NMR. We found promising activity against human nonsmall cell lung cancer (NCI-H460) cells with IC50 values for growth inhibition of 5 fiM per bisphosphonate ligand. The effects of bisphosphonate complexation on IC50 decreased with increasing bisphosphonate chain length: C-0 approximate to 6.1x, C-6 approximate to 3.4x, and C8 approximate to 1.1x. We then determined the activity of One of the most potent compounds in the series, Mo(4)Zol(2)Mn(III), against SK-ES-1 sarcoma cells in a mouse xenograft system finding a similar to 5x decrease in tumor volume than found with the parent compound zoledronate at the same compound dosing, (5 mu g/mouse). Overall, the, results are of interest since we show for the first time that heteropolyoxomolybdate-bisphosphonate hybrids kill tumor cells in vitro and significantly decrease tumor growth) in-vivo, opening up new possibilities for targeting both Ras as, well as epidermal growth factor receptor driyen cancers.
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