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American Chemical Society, Journal of Medicinal Chemistry, 11(55), p. 5601-5613, 2012

DOI: 10.1021/jm3005459

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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

Journal article published in 2012 by Alfred A. Hummer, Caroline Bartel, Vladimir B. Arion, Michael A. Jakupec ORCID, Wolfram Meyer-Klaucke, Tina Geraki, Paul D. Quinn, Ana Mijovilovich, Bernhard K. Keppler, Annette Rompel
This paper was not found in any repository; the policy of its publisher is unknown or unclear.
This paper was not found in any repository; the policy of its publisher is unknown or unclear.

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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.