Interaction of the anticancer gallium(III) complexes of 8-hydroxyquinoline and maltol with human serum proteins

Verfasser / Beitragende:
[Éva Enyedy, Orsolya Dömötör, Krisztina Bali, Anasztázia Hetényi, Tiziano Tuccinardi, Bernhard Keppler]
Ort, Verlag, Jahr:
2015
Enthalten in:
JBIC Journal of Biological Inorganic Chemistry, 20/1(2015-01-01), 77-88
Format:
Artikel (online)
ID: 605506884
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024 7 0 |a 10.1007/s00775-014-1211-9  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00775-014-1211-9 
245 0 0 |a Interaction of the anticancer gallium(III) complexes of 8-hydroxyquinoline and maltol with human serum proteins  |h [Elektronische Daten]  |c [Éva Enyedy, Orsolya Dömötör, Krisztina Bali, Anasztázia Hetényi, Tiziano Tuccinardi, Bernhard Keppler] 
520 3 |a Tris(8-quinolinolato)gallium(III) (KP46) and tris(maltolato)gallium(III) (GaM) are promising orally active antitumor metallodrugs currently undergoing clinical trials. Their interaction with human serum albumin (HSA) and transferrin (Tf) was studied in detail in aqueous solution by the combination of various methods such as spectrofluorometry, UV-vis spectrophotometry, 1H and saturation transfer difference NMR spectroscopy, and ultrafiltration-UV-vis spectrophotometry. Binding data were evaluated quantitatively. Tf was found to replace the original ligand much less efficiently in KP46 than in GaM, whereas a significant noncovalent binding of KP46 with HSA (log K′=4.04) retaining the coordination environment around gallium(III) was found. The interaction between HSA and KP46 was also confirmed by protein-complex modeling calculations. On the basis of the conditional stability constants, the distribution of gallium(III) in serum was computed and compared for these metallodrugs under physiological conditions, and revealed the prominent role of HSA in the case of KP46 and that of Tf for GaM. Graphical abstract: 
540 |a SBIC, 2014 
690 7 |a Solution equilibrium  |2 nationallicence 
690 7 |a Albumin  |2 nationallicence 
690 7 |a Transferrin  |2 nationallicence 
690 7 |a Binding affinity  |2 nationallicence 
690 7 |a Fluorescence  |2 nationallicence 
690 7 |a apoTf : Apotransferrin  |2 nationallicence 
690 7 |a GaM : Tris(3-hydroxy-2-methyl-4H-pyran-4-onato)gallium(III)  |2 nationallicence 
690 7 |a HEPES : 4-(2-Hydroxyethyl)-1-piperazineethanesulfonic acid  |2 nationallicence 
690 7 |a HMM : High molecular mass  |2 nationallicence 
690 7 |a HSA : Human serum albumin  |2 nationallicence 
690 7 |a HQ : 8-Hydroxyquinoline  |2 nationallicence 
690 7 |a KP46 : Tris(8-quinolinolato)gallium(III)  |2 nationallicence 
690 7 |a LMM : Low molecular mass  |2 nationallicence 
690 7 |a PDB : Protein Data Bank  |2 nationallicence 
690 7 |a STD : Saturation transfer difference  |2 nationallicence 
690 7 |a Tf : Human serum transferrin  |2 nationallicence 
700 1 |a Enyedy  |D Éva  |u Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, 6720, Szeged, Hungary  |4 aut 
700 1 |a Dömötör  |D Orsolya  |u Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, 6720, Szeged, Hungary  |4 aut 
700 1 |a Bali  |D Krisztina  |u Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, 6720, Szeged, Hungary  |4 aut 
700 1 |a Hetényi  |D Anasztázia  |u Department of Medical Chemistry, University of Szeged, Dóm tér 8, 6720, Szeged, Hungary  |4 aut 
700 1 |a Tuccinardi  |D Tiziano  |u Department of Pharmacy, University of Pisa, 56126, Pisa, Italy  |4 aut 
700 1 |a Keppler  |D Bernhard  |u Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 42, 1090, Vienna, Austria  |4 aut 
773 0 |t JBIC Journal of Biological Inorganic Chemistry  |d Springer Berlin Heidelberg  |g 20/1(2015-01-01), 77-88  |x 0949-8257  |q 20:1<77  |1 2015  |2 20  |o 775 
856 4 0 |u https://doi.org/10.1007/s00775-014-1211-9  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00775-014-1211-9  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Enyedy  |D Éva  |u Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, 6720, Szeged, Hungary  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Dömötör  |D Orsolya  |u Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, 6720, Szeged, Hungary  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Bali  |D Krisztina  |u Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, 6720, Szeged, Hungary  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Hetényi  |D Anasztázia  |u Department of Medical Chemistry, University of Szeged, Dóm tér 8, 6720, Szeged, Hungary  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Tuccinardi  |D Tiziano  |u Department of Pharmacy, University of Pisa, 56126, Pisa, Italy  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Keppler  |D Bernhard  |u Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 42, 1090, Vienna, Austria  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t JBIC Journal of Biological Inorganic Chemistry  |d Springer Berlin Heidelberg  |g 20/1(2015-01-01), 77-88  |x 0949-8257  |q 20:1<77  |1 2015  |2 20  |o 775