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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

DOI: 10.1021/jm3005459 DOI Help

Authors: Alfred Hummer (Universitat Wien) , Caroline Bartel (Universität Wien, Austria) , Vladimir B. Arion (Universität Wien, Austria) , Michael A. Jakupec (Universität Wien, Austra) , Wolfram Meyer-klaucke (University Paderborn) , Tina Geraki (Diamond Light Source) , Paul Quinn (Diamond Light Source) , Ana Mijovilovich (University of Utrecht) , Bernhard K. Keppler (Universität Wien, Austria) , Annette Rompel (Universitat Wien)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Medicinal Chemistry , VOL 55 (11) , PAGES 5601 - 5613

State: Published (Approved)
Published: June 2012
Diamond Proposal Number(s): 6303

Abstract: Tris(8-quinolinolato)gallium(III) (1, KP46) 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 (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.

Journal Keywords: X-ray absorption spectroscopy; gallium compound; anticancer drug; serum protein; elemental distribution pattern

Subject Areas: Chemistry, Medicine

Instruments: I18-Microfocus Spectroscopy

Other Facilities: DESY - Deutsches Elektronen Synchrotron, Hamburg