Sobczak-Kupiec Agnieszka, Beata Kaźmierska, P. Świątek, Izabela Muszalska-Kolos
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引用次数: 0
Abstract
Phenothiazine and its derivatives exhibit many properties. Hence they are the starting structures
for many new potential drugs, biologically active compounds, dyes, etc. In this paper, we
investigated a series of five fluphenazine analogs synthesized exhibiting inhibition of multidrug
resistance (MDR) in tumor cells. During the drug discovery process, the determination of
physicochemical properties of new compounds, such as dissociation constant values (pKa), is
essential because it directly affects their pharmacokinetic profile. Thus, this study aimed to
determine the pKa values of fluphenazine and its derivatives from the mobile phase pH
dependence of the retention factor with the reverse phase liquid chromatographic method.
Binary mixtures of phosphate buffer (pH 2.3-11.5) and acetonitrile (40-55%) in different
percentages and the Gemini NX C18 column as the stationary phase were used in the tests. The
pKa' values of fluphenazine derivatives at experimental concentrations of organic solvent were
determined based on the obtained sigmoidal k curves as a function of pH. Then these values
were extrapolated to 0% acetonitrile to obtain the actual pKa values. Moreover, a comparative
evaluation of chromatographically obtained and computationally calculated pKa parameters
was carried out.
期刊介绍:
The international journal of the Polish Pharmaceutical Society is published in 6 issues a year. The journal offers Open Access publication of original research papers, short communications and reviews written in English, in all areas of pharmaceutical sciences. The following areas of pharmaceutical sciences are covered: Analysis, Biopharmacy, Drug Biochemistry, Drug Synthesis, Natural Drugs, Pharmaceutical Technology, Pharmacology and General.
A bimonthly appearing in English since 1994, which continues “Acta Poloniae Pharmaceutica”, whose first issue appeared in December 1937. The war halted the activity of the journal’s creators. Issuance of “Acta Poloniae Pharmaceutica” was resumed in 1947. From 1947 the journal appeared irregularly, initially as a quarterly, then a bimonthly. In the years 1963 – 1973 alongside the Polish version appeared the English edition of the journal. Starting from 1974 only works in English are published in the journal. Since 1995 the journal has been appearing very regularly in two-month intervals (six books a year). The journal publishes original works from all fields of pharmacy, summaries of postdoctoral dissertations and laboratory notes.