Effects of structural modification of the daunosamine moiety of anthracycline antibiotics on pK a values determined by capillary zone electrophoresis

The thermodynamic acid dissociation constants (pK and pK ) of 16 anthracycline antibiotics, including doxorubicin (DOX) and daunorubicin (DAU), their epimers, epidoxorubicin (EDOX) and epidaunorubicin (EDAU), as well as novel anthracycline derivatives containing piperidine (FPIP), morpholine (FMOR)...

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Bibliographic Details
Published in:Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2017-08, Vol.1060, p.44
Main Authors: Matyjaszczyk, Karolina, Kolonko, Marta, Gonciarz-Dytman, Anna, Oszczapowicz, Irena, Łukawska, Małgorzata, Jawień, Wojciech, Chlopicki, Stefan, Walczak, Maria
Format: Article
Language:English
Subjects:
Amidines
Anthracyclines - chemistry
Anthracyclines - pharmacology
Antibiotics, Antineoplastic - chemistry
Antibiotics, Antineoplastic - pharmacology
Cell Line, Tumor
Cell Proliferation - drug effects
Electrophoresis, Capillary - methods
Hexosamines - chemistry
Hexosamines - pharmacology
Humans
Hydrogen-Ion Concentration
Nonlinear Dynamics
Thermodynamics
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Summary:The thermodynamic acid dissociation constants (pK and pK ) of 16 anthracycline antibiotics, including doxorubicin (DOX) and daunorubicin (DAU), their epimers, epidoxorubicin (EDOX) and epidaunorubicin (EDAU), as well as novel anthracycline derivatives containing piperidine (FPIP), morpholine (FMOR) and hexamethylenoimine (FHEX) rings in the formamidine group of the daunosamine moiety were determined by analysis of the dependence between measured electrophoretic mobility and the pH of the buffer using the capillary zone electrophoresis method. The results obtained confirmed the ampholytic character of anthracyclines with at least two ionization states. The determined values were in the range of 8.36-9.28 and 9.38-11.48 for pK and pK arising from ionization of amino and phenolic groups, respectively. Structural modifications in the daunosamine moiety of the studied anthracyclines affected their pharmacological properties, such as antiproliferative activity.
ISSN:1873-376X
DOI:10.1016/j.jchromb.2017.04.038