Anticancer Activity of Polyoxometalate-Bisphosphonate Complexes: Synthesis, Characterization, In Vitro and In Vivo Results.
Inorg Chem
; 56(13): 7558-7565, 2017 Jul 03.
Article
em En
| MEDLINE
| ID: mdl-28631925
ABSTRACT
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 â¼5 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 â¼5× decrease in tumor volume than found with the parent compound zoledronate at the same compound dosing (5 µg/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 driven cancers.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Organometálicos
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Compostos de Tungstênio
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Difosfonatos
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Inorg Chem
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
França