Study of the physicochemical properties of protein kinase CK2 inhibitors -TBBt, TBBi and 2-Me-TBBi

Edyta Łukowska-Chojnacka , Aneta Pobudkowska-Mirecka , Maria Bretner

Abstract

The examination of physicochemical properties of selected protein kinase CK2 inhibitors: 4,5,6,7-tetrabromo-1H-benzotriazole (TBBt), 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi) and 4,5,6,7-tetrabromo-2-methyl-1H-benzimidazole (2-Me-TBBi) was performed. The study includes modification of synthesis method and determination of compounds' thermal properties, the solid-liquid phase equilibria and pKa. Thermal properties (melting temperature, enthalpy of fusion, temperature and enthalpy of phase transitions) were determined by means of differential scanning calorimetry (DSC). For solid-liquid phase equilibria study, as a solvent, three liquids were used independently: water, ethanol and 1-octanol. In order to elicit the inhibitors’ solubility with alcohols (ethanol and 1-octanol), the dynamic method was applied. In the case of poorly soluble inhibitors in water, equilibria were determined by spectrophotometric method. Based on a phase diagram obtained results were interpreted and correlated using three equations: Wilson equation, NRTL equation and UNIQUAC equation. pKa values of studied polybrominated benzoazoles were estimated by the spectrophotometric Bates–Schwarzenbach method at two constant temperatures: 298.15 K as a room temperature and 310.15 K as a human body temperature. Obtained results are very important for further design of CK2 inhibitors, because they provide information about the solubility of pharmacophore in binary systems: active compound (1) + solvent (2), that may be used in differentiating the way how to apply potential drug. Moreover, all values of dissociation constants bring valuable guidelines to establish the therapeutic dose of pharmaceutics.
Author Edyta Łukowska-Chojnacka (FC / CDSB)
Edyta Łukowska-Chojnacka,,
- Chair of Drug and Cosmetics Biotechnology
, Aneta Pobudkowska-Mirecka (FC / DPC)
Aneta Pobudkowska-Mirecka,,
- Department Of Physical Chemistry
, Maria Bretner (FC / CDSB)
Maria Bretner,,
- Chair of Drug and Cosmetics Biotechnology
Journal seriesFluid Phase Equilibria, ISSN 0378-3812, (A 30 pkt)
Issue year2019
Vol479
Pages52-62
Publication size in sheets0.5
Keywords in EnglishActive pharmaceutical ingredientsDifferential scanning microcalorimetrySolubilityBates-Schwarzenbach methodThermodynamic correlationThermophysical properties
ASJC Classification1606 Physical and Theoretical Chemistry; 3100 General Physics and Astronomy; 1500 General Chemical Engineering
DOIDOI:10.1016/j.fluid.2018.09.015
URL https://www.sciencedirect.com/science/article/pii/S0378381218303959
Languageen angielski
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1-s2.0-S0378381218303959-main.pdf 867.84 KB
Score (nominal)30
ScoreMinisterial score = 30.0, 26-04-2019, ArticleFromJournal
Ministerial score (2013-2016) = 30.0, 11-03-2019, ArticleFromJournal
Publication indicators Scopus Citations = 1; Scopus SNIP (Source Normalised Impact per Paper): 2017 = 1.033; WoS Impact Factor: 2017 = 2.197 (2) - 2017=2.214 (5)
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