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Affinity of Antifungal Isoxazolo[3,4-b]pyridine-3(1H)-Ones to Phospholipids in Immobilized Artificial Membrane (IAM) Chromatography

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 usi...

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Autores principales: Ciura, Krzesimir, Fedorowicz, Joanna, Žuvela, Petar, Lovrić, Mario, Kapica, Hanna, Baranowski, Paweł, Sawicki, Wiesław, Wong, Ming Wah, Sączewski, Jarosław
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587931/
https://www.ncbi.nlm.nih.gov/pubmed/33092252
http://dx.doi.org/10.3390/molecules25204835
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author Ciura, Krzesimir
Fedorowicz, Joanna
Žuvela, Petar
Lovrić, Mario
Kapica, Hanna
Baranowski, Paweł
Sawicki, Wiesław
Wong, Ming Wah
Sączewski, Jarosław
author_facet Ciura, Krzesimir
Fedorowicz, Joanna
Žuvela, Petar
Lovrić, Mario
Kapica, Hanna
Baranowski, Paweł
Sawicki, Wiesław
Wong, Ming Wah
Sączewski, Jarosław
author_sort Ciura, Krzesimir
collection PubMed
description 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.
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spelling pubmed-75879312020-10-29 Affinity of Antifungal Isoxazolo[3,4-b]pyridine-3(1H)-Ones to Phospholipids in Immobilized Artificial Membrane (IAM) Chromatography Ciura, Krzesimir Fedorowicz, Joanna Žuvela, Petar Lovrić, Mario Kapica, Hanna Baranowski, Paweł Sawicki, Wiesław Wong, Ming Wah Sączewski, Jarosław Molecules Communication 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. MDPI 2020-10-20 /pmc/articles/PMC7587931/ /pubmed/33092252 http://dx.doi.org/10.3390/molecules25204835 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Ciura, Krzesimir
Fedorowicz, Joanna
Žuvela, Petar
Lovrić, Mario
Kapica, Hanna
Baranowski, Paweł
Sawicki, Wiesław
Wong, Ming Wah
Sączewski, Jarosław
Affinity of Antifungal Isoxazolo[3,4-b]pyridine-3(1H)-Ones to Phospholipids in Immobilized Artificial Membrane (IAM) Chromatography
title Affinity of Antifungal Isoxazolo[3,4-b]pyridine-3(1H)-Ones to Phospholipids in Immobilized Artificial Membrane (IAM) Chromatography
title_full Affinity of Antifungal Isoxazolo[3,4-b]pyridine-3(1H)-Ones to Phospholipids in Immobilized Artificial Membrane (IAM) Chromatography
title_fullStr Affinity of Antifungal Isoxazolo[3,4-b]pyridine-3(1H)-Ones to Phospholipids in Immobilized Artificial Membrane (IAM) Chromatography
title_full_unstemmed Affinity of Antifungal Isoxazolo[3,4-b]pyridine-3(1H)-Ones to Phospholipids in Immobilized Artificial Membrane (IAM) Chromatography
title_short Affinity of Antifungal Isoxazolo[3,4-b]pyridine-3(1H)-Ones to Phospholipids in Immobilized Artificial Membrane (IAM) Chromatography
title_sort affinity of antifungal isoxazolo[3,4-b]pyridine-3(1h)-ones to phospholipids in immobilized artificial membrane (iam) chromatography
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587931/
https://www.ncbi.nlm.nih.gov/pubmed/33092252
http://dx.doi.org/10.3390/molecules25204835
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