X-ray Absorption Spectroscopy of an Investigational Anticancer Gallium(III) Drug: Interaction with Serum Proteins, Elemental Distribution Pattern, and Coordination of the Compound in Tissue
- Author(s)
- Alfred Hummer, Caroline Bartel, Vladimir Arion, Michael Jakupec, Wolfram Meyer-Klaucke, Tina Geraki, Paul P. Quinn, Ana Mijovilovich, Bernhard Keppler, Annette Rompel
- Abstract
Tris(8-quinolinolato)gallium(III) (1, K246) is a very promising investigational anticancer drug. Its interaction with serum proteins, elemental distribution, and coordination in tissue were investigated with X-ray absorption (XAS) methods. Model compounds with mixed O, N, and/or S donor atoms are reported. The coordination and structure of 1 in cell culture medium (minimum essential medium, MEM) and fetal calf serum (FCS) were probed by XANES and EXAFS. The interaction of 1 with the serum proteins apotransferrin energy (apoTf) and human serum albumin (HSA) was addressed as well. By application of micro-XAS to tissue samples from mice treated with 1, the gallium distribution pattern was analyzed and compared to those of physiological trace elements. The complex 1 turned out to be very stable under physiological conditions, in cell culture media and in tissue samples. The coordination environment of the metal center remains intact in the presence of apoTf and HSA. The gallium distribution pattern in tumor and liver tissue revealed high similarities to the distribution patterns of Zn and Fe, minor similarities to Cu and Ni, and no similarity to Ca.
- Organisation(s)
- Department of Biophysical Chemistry, Department of Inorganic Chemistry
- External organisation(s)
- European Molecular Biology Laboratory, Diamond Light Source Ltd, Utrecht University
- Journal
- Journal of Medicinal Chemistry
- Volume
- 55
- Pages
- 5601-5613
- No. of pages
- 13
- ISSN
- 0022-2623
- Publication date
- 2012
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 301305 Medical chemistry, 301204 Pharmacognosy
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/acfab2ac-d8a7-457c-a5e5-cc278732af19