Geminal bisphosphonates (BPs), used in the clinic for the treatment of hypercalcaemia and skeletal metastases, have been also exploited for promoting the specific accumulation of platinum antitumor drugs in bone tissue. In this work, the platinum dinuclear complex [{Pt(en)}2(μ-AHBP-H2)]+ (1) (the carbon atom bridging the two phosphorous atoms carrying a 2-ammonioethyl and a hydroxyl group, AHBP-H2) has been used as scaffold for the synthesis of a Pt(II) trinuclear complex, [{Pt(en)}3(μ-AHBP)]+ (2), and a Pt(IV) adamantane-shaped dinuclear complex featuring an oxo-bridge, [{PtIV(en)Cl}2(μ-O)(μ-AHBP-H2)]+ (3) (X-ray structure). Compound 2 undergoes a reversible, pH dependent, rearrangement with a neat switch point around pH = 5.4. Compound 3 undergoes a one-step electrochemical reduction at Epc = −0.84 V affording compound 1. Such a potential is far lower than that of glutathione (−0.24 V), nevertheless compound 3 can undergo chemical reduction to 1 by GSH, most probably through a different (inner-sphere) mechanism. In vitro cytotoxicity of the new compounds, tested against murine glioma (C6) and human cervix (HeLa) and hepatoma (HepG2) cell lines, has shown that, while the PtIV dimer 3 is inactive up to a concentration of 50 μM, the two PtII polynuclear compounds 1 and 2 have a cytotoxicity comparable to that of cisplatin with the trinuclear complex 2 generally more active than the dinuclear complex 1.

Dinuclear Pt(II)-bisphosphonate complexes: a scaffold for multinuclear or different oxidation state platinum drugs.

MARGIOTTA, NICOLA;PACIFICO, Concetta;LOPALCO, ANTONIO;DENORA, NUNZIO;NATILE, Giovanni
2012

Abstract

Geminal bisphosphonates (BPs), used in the clinic for the treatment of hypercalcaemia and skeletal metastases, have been also exploited for promoting the specific accumulation of platinum antitumor drugs in bone tissue. In this work, the platinum dinuclear complex [{Pt(en)}2(μ-AHBP-H2)]+ (1) (the carbon atom bridging the two phosphorous atoms carrying a 2-ammonioethyl and a hydroxyl group, AHBP-H2) has been used as scaffold for the synthesis of a Pt(II) trinuclear complex, [{Pt(en)}3(μ-AHBP)]+ (2), and a Pt(IV) adamantane-shaped dinuclear complex featuring an oxo-bridge, [{PtIV(en)Cl}2(μ-O)(μ-AHBP-H2)]+ (3) (X-ray structure). Compound 2 undergoes a reversible, pH dependent, rearrangement with a neat switch point around pH = 5.4. Compound 3 undergoes a one-step electrochemical reduction at Epc = −0.84 V affording compound 1. Such a potential is far lower than that of glutathione (−0.24 V), nevertheless compound 3 can undergo chemical reduction to 1 by GSH, most probably through a different (inner-sphere) mechanism. In vitro cytotoxicity of the new compounds, tested against murine glioma (C6) and human cervix (HeLa) and hepatoma (HepG2) cell lines, has shown that, while the PtIV dimer 3 is inactive up to a concentration of 50 μM, the two PtII polynuclear compounds 1 and 2 have a cytotoxicity comparable to that of cisplatin with the trinuclear complex 2 generally more active than the dinuclear complex 1.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11586/123208
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 24
  • ???jsp.display-item.citation.isi??? 24
social impact