Inductively coupled plasma mass spectrometry for metallodrug development: Albumin binding and serum distribution of cytotoxic cis- and trans-isomeric platinum(II) complexes.

Inductively coupled plasma mass spectrometry for metallodrug development: Albumin binding and serum distribution of cytotoxic cis- and trans-isomeric platinum(II) complexes.
J Inorg Biochem. 2014 Apr 22;137C:40-45
Authors: Ossipov K, Scaffidi-Domianello YY, Seregina IF, Galanski M, Keppler BK, Timerbaev AR, Bolshov MA
Abstract
Binding to plasma proteins is one of the major metabolic pathways of metallodrugs. In the case of platinum-based anticancer drugs, it is the interaction with serum albumin that affects most strongly their in vivo behavior. Since both the configuration, i.e. cis-trans-isomerism, and the nature of leaving groups have an effect on the reactivity of Pt(II) coordination compounds toward biomolecules, a set of cis- and trans-configured complexes with halide leaving groups (Cl(-), Br(-), and I(-)) and 2-propanone oxime as carrier ligands was chosen for this study. Binding experiments were performed both with albumin and human serum and the Pt content in ultrafiltrates was quantified using inductively coupled plasma mass spectrometry. In order to shed light on the binding mechanism, the albumin binding constant (KHSA) and the octanol-water partition coefficient (P) were experimentally determined and relationships between log KHSA and log P were explored. The correlation was found significant only for cis-configured platinum complexes (R(2)=0.997 and standard deviation=0.02), indicating a certain contribution of the non...

Source: Journal of Inorganic Biochemistry - April 22, 2014 Category: Biochemistry Authors: Ossipov K, Scaffidi-Domianello YY, Seregina IF, Galanski M, Keppler BK, Timerbaev AR, Bolshov MA Tags: J Inorg Biochem Source Type: research