Inductively coupled plasma mass spectrometry for metallodrug development
- Author(s)
- Konstantin Ossipov, Yulia Y. Scaffidi-Domianello, Irina F. Seregina, Mathea Sophia Galanski, Bernhard K. Keppler, Andrei R. Timerbaev, Mikhail A. Bolshov
- 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 (K
HSA) and the octanol-water partition coefficient (P) were experimentally determined and relationships between log K
HSA 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 nonspecific binding which is largely dominated by the lipophilicity of compounds. In contrast, for trans-complexes a specific molecular recognition element plays a significant role. The participation of albumin in drug distribution in blood serum was assessed using an equilibrium distribution model and by comparing the percentage binding in the albumin and serum-protein fractions. Irrespective of the compound polarity, albumin contributes from 85 to 100% to the overall binding in serum.
- Organisation(s)
- Department of Inorganic Chemistry
- External organisation(s)
- Anuchin Research Institute and Museum of Anthropology, Russian Academy of Sciences
- Journal
- Journal of Inorganic Biochemistry
- Volume
- 137
- Pages
- 40-45
- No. of pages
- 6
- ISSN
- 0162-0134
- DOI
- https://doi.org/10.1016/j.jinorgbio.2014.04.008
- Publication date
- 08-2014
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 301303 Medical biochemistry
- Keywords
- ASJC Scopus subject areas
- Biochemistry, Inorganic Chemistry
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/a0b493d6-1dc8-4812-8511-61b6b3878e44