期刊
DALTON TRANSACTIONS
卷 -, 期 48, 页码 10904-10913出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/b919721d
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资金
- Universities of Bari and Padova
- Italian Ministero dell'Universita e della Ricerca (MUR) [PRIN 20078EWK9B]
- EC [D39/0004/06]
- Inter-University Consortium for Research on the Chemistry of Metal Ions in Biological Systems (C.I.R.C.M.S.B.)
For over 30 years cisplatin has been one of the most active antitumour agents in clinical use, nevertheless research for overcoming cisplatin toxicity and resistance or for improving its efficacy has never ceased. In this context we have recently proposed dinuclear Pt complexes with bridging geminal bisphosphonates as novel Pt-prodrugs with potential activity at the bone surface after embedment in inorganic matrices and implantation at the tumour site. In the present paper we report the synthesis and full characterization of four new platinum complexes having a dinuclear structure with a bisphosphonate (2-ammonium-1-hydroxyethane-1,1-diyl-bisphosphonate or 3-ammonium-1-hydroxypropane-1,1-diyl-bisphosphonate, AHBP-H and PAM-H, respectively) acting as a bridging ligand between two platinum moieties (cis-[Pt(NH3)(2)](2+), directly related to cisplatin, and [Pt(cis-1,4-DACH)](2+), known to be able to overcome the cisplatin resistance). Moreover, as a preliminary investigation, the in vitro cytotoxicity of the new complexes has been evaluated on a panel of 13 human tumour cell lines including cisplatin-and multidrug-resistant sublines.
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