Probing the interactions of cytotoxic [Pt(1S,2S-DACH)(5,6-dimethyl-1,10-phenanthroline)] and its PtIV derivatives with human serum

Benjamin W. J. Harper, Aviva Friedman-Ezra, Roman Sirota, Emanuele Petruzzella, Janice R. Aldrich-Wright, Dan Gibson

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10 Citations (Scopus)

Abstract

The discrepancy between the in vitro cytotoxic results and the in vivo performance of Pt56MeSS, prompted us to look into its interactions and those of its Pt(IV) derivatives with human serum, HSA, lipoproteins and serum supplemented cell culture medium. The Pt(II) complex, Pt56MeSS, binds non-covalently and reversibly to slow tumbling proteins in human serum and in cell culture medium and interacts through the phenanthroline with HSA with a Kd of about 1.5 x 10-6. All Pt(IV) complexes were stable to reduction in HS but those with axial carboxylate ligands, cct-[Pt(1S,2S-DACH)(5,6-dimethyl-1,10-phenantroline)(acetato)2](TFA)2 (Pt56MeSS(OAc)2) and cct-[Pt(1S,2S-DACH)(5,6-dimehtyl-1,10-phenantroline)(phenylbutyrate)2](TFA)2 (Pt56MeSS(PhB)2), were spontaneously reduced at pH=7 or higher in phosphate buffer, but not in tris buffer (pH=8). HS also retarded the rate of reduction by ascorbate of the Pt(IV) complexes compared with the rates of reduction in phosphate buffer suggesting that for this class of compounds, phosphate buffer is not a good model for HS.
Original languageEnglish
Pages (from-to)510-519
Number of pages10
JournalChemMedChem
Volume12
Issue number7
DOIs
Publication statusPublished - 2017

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Keywords

  • antineoplastic agents
  • lipoproteins
  • platinum

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