Matyjaszczyk Karolina, Kolonko Marta, Gonciarz-Dytman Anna, Oszczapowicz Irena, Łukawska Małgorzata, Jawień Wojciech, Chlopicki Stefan, Walczak Maria
Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzyńskiego 14, 30-348 Kraków, Poland; Chair and Department of Toxicology, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
Department of Biochemistry, Faculty of Chemistry, Wrocław University of Technology, Wybrzeże Wyspiańskiego 27, 50-370, Wrocław, Poland.
J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Aug 15;1060:44-52. doi: 10.1016/j.jchromb.2017.04.038. Epub 2017 Apr 24.
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.
采用毛细管区带电泳法，通过分析所测电泳迁移率与缓冲液pH值之间的关系，测定了16种蒽环类抗生素的热力学酸解离常数（pK和pK），这些抗生素包括多柔比星（DOX）、柔红霉素（DAU）及其差向异构体表柔比星（EDOX）和表柔红霉素（EDAU），以及在柔红糖胺部分的脒基中含有哌啶（FPIP）、吗啉（FMOR）和六亚甲基亚胺（FHEX）环的新型蒽环类衍生物。所得结果证实了蒽环类抗生素具有至少两种电离状态的两性特征。氨基和酚羟基电离产生的pK和pK的测定值分别在8.36 - 9.28和9.38 - 11.48范围内。所研究蒽环类抗生素柔红糖胺部分的结构修饰影响了它们的药理性质，如抗增殖活性。
