Affinity of Antifungal Isoxazolo[3,4-b]pyridine-3(1H)-Ones to Phospholipids in Immobilized Artificial Membrane (IAM) Chromatography
| Autor: | Jarosław Sączewski, Joanna Fedorowicz, Petar Žuvela, Mario Lovrić, Ming Wah Wong, Paweł Baranowski, Hanna Kapica, Wiesław Sawicki, Krzesimir Ciura |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Octanol
isoxazolo[3 4-b]pyridin-3(1H)-one isoxazolone Antifungal Agents Pyridines Pyridones immobilized artificial membrane IAM-HPLC isoxazolo[3 4-b]pyridin-3(1H)-one Synthetic membrane Pharmaceutical Science Context (language use) 01 natural sciences Analytical Chemistry lcsh:QD241-441 chemistry.chemical_compound lcsh:Organic chemistry Drug Discovery Pyridine Partial least squares regression Physical and Theoretical Chemistry Chromatography High Pressure Liquid Phospholipids Chromatography Reverse-Phase Chromatography 010405 organic chemistry Chemistry Communication Organic Chemistry Water Membranes Artificial Biological activity Reversed-phase chromatography 1-Octanol Hydrogen-Ion Concentration 0104 chemical sciences 010404 medicinal & biomolecular chemistry Chemistry (miscellaneous) Lipophilicity Molecular Medicine Hydrophobic and Hydrophilic Interactions |
| Zdroj: | Molecules, Vol 25, Iss 4835, p 4835 (2020) Molecules |
| ISSN: | 1420-3049 |
| Popis: | Currently, rapid evaluation of the physicochemical parameters of drug candidates, such as lipophilicity, is in high demand owing to it enabling the approximation of the processes of absorption, distribution, metabolism, and elimination. Although the lipophilicity of drug candidates is determined using the shake flash method (n-octanol/water system) or reversed phase liquid chromatography (RP-LC), more biosimilar alternatives to classical lipophilicity measurement are currently available. One of the alternatives is immobilized artificial membrane (IAM) chromatography. The present study is a continuation of our research focused on physiochemical characterization of biologically active derivatives of isoxazolo[3,4-b]pyridine-3(1H)-ones. The main goal of this study was to assess the affinity of isoxazolones to phospholipids using IAM chromatography and compare it with the lipophilicity parameters established by reversed phase chromatography. Quantitative structure–retention relationship (QSRR) modeling of IAM retention using differential evolution coupled with partial least squares (DE-PLS) regression was performed. The results indicate that in the studied group of structurally related isoxazolone derivatives, discrepancies occur between the retention under IAM and RP-LC conditions. Although some correlation between these two chromatographic methods can be found, lipophilicity does not fully explain the affinities of the investigated molecules to phospholipids. QSRR analysis also shows common factors that contribute to retention under IAM and RP-LC conditions. In this context, the significant influences of WHIM and GETAWAY descriptors in all the obtained models should be highlighted. |
| Databáze: | OpenAIRE |
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