title: Probing the Interactions of Cytotoxic [Pt(1S,2S-DACH)(5,6-dimethyl-1,10-phenanthroline)] and Its PtIVDerivatives with Human Serum.
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 PtIVderivatives with human serum (HS), human serum albumin (HSA), lipoproteins, and serum-supplemented cell culture media. The PtIIcomplex, Pt56MeSS, binds noncovalently and reversibly to slow-tumbling proteins in HS and in cell culture media and interacts through the phenanthroline group with HSA, with a Kdvalue of ∼1.5×10-6m. All PtIVcomplexes were found to be stable toward 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)(phenylbutyrato)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 decreased the rate of reduction by ascorbate of the PtIVcomplexes relative to the reduction rates in phosphate buffer, suggesting that for this compound class, phosphate buffer is not a good model for HS.
authors.affiliation: Institute for Drug Research, School of Pharmacy, The Hebrew University, Jerusalem, 91120, Israel.
authors.forename: Benjamin W J
authors.initials: BW
authors.lastname: Harper
authors.affiliation: Institute for Drug Research, School of Pharmacy, The Hebrew University, Jerusalem, 91120, Israel.
authors.forename: Aviva
authors.initials: A
authors.lastname: Friedman-Ezra
authors.affiliation: Institute for Drug Research, School of Pharmacy, The Hebrew University, Jerusalem, 91120, Israel.
authors.forename: Roman
authors.initials: R
authors.lastname: Sirota
authors.affiliation: Institute for Drug Research, School of Pharmacy, The Hebrew University, Jerusalem, 91120, Israel.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Petruzzella
authors.affiliation: School of Science and Health, Western Sydney University, Penrith South DC, 1797, NSW, Australia.
authors.forename: Janice R
authors.initials: JR
authors.lastname: Aldrich-Wright
authors.affiliation: Institute for Drug Research, School of Pharmacy, The Hebrew University, Jerusalem, 91120, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Gibson
mesh_terms: D001205:Ascorbic Acid / Q000737:chemistry; D056831:Coordination Complexes / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry*; D003514:Cyclohexylamines / Q000737:chemistry; D004355:Drug Stability; D055664:Electrochemical Techniques; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D010618:Phenanthrolines / Q000737:chemistry; D010984:Platinum / Q000737:chemistry*; D000091402:Prohibitins
chemical_list: D056831:Coordination Complexes; D003514:Cyclohexylamines; C000717328:PHB protein, human; C000717331:PHB2 protein, human; D010618:Phenanthrolines; D000091402:Prohibitins; D010984:Platinum; C030435:1,2-cyclohexanediamine; D001205:Ascorbic Acid; C025205:1,10-phenanthroline
keywords: DNA; human serum; platinum drugs; reduction; stability