Predicting the Blood-Brain Barrier Permeability of New Drug-Like Compounds via HPLC with Various Stationary Phases
The permeation of the blood-brain barrier is a very important consideration for new drug candidate molecules. In this research, the reversed-phase liquid chromatography with different columns (Purosphere RP-18e, IAM.PC.DD2 and Cosmosil Cholester) was used to predict the penetration of the blood-brai...
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doaj-65ce16841aad48e2af4d8cc8626e2ecb2020-11-25T01:45:51ZengMDPI AGMolecules1420-30492020-01-0125348710.3390/molecules25030487molecules25030487Predicting the Blood-Brain Barrier Permeability of New Drug-Like Compounds via HPLC with Various Stationary PhasesMałgorzata Janicka0Małgorzata Sztanke1Krzysztof Sztanke2Department of Physical Chemistry, Faculty of Chemistry, Institute of Chemical Science, Maria Curie-Skłodowska University, Maria Curie-Skłodowska Sq. 3, 20-031 Lublin, PolandChair and Department of Medical Chemistry, Medical University, 4A Chodźki Street, 20-093 Lublin, PolandLaboratory of Bioorganic Synthesis and Analysis, Chair and Department of Medical Chemistry, Medical University, 4A Chodźki Street, 20-093 Lublin, PolandThe permeation of the blood-brain barrier is a very important consideration for new drug candidate molecules. In this research, the reversed-phase liquid chromatography with different columns (Purosphere RP-18e, IAM.PC.DD2 and Cosmosil Cholester) was used to predict the penetration of the blood-brain barrier by 65 newly-synthesized drug-like compounds. The linear free energy relationships (LFERs) model (log <i>BB</i> = <i>c</i> + <i>eE</i> + <i>sS</i> + <i>aA</i> + <i>bB</i> + <i>vV</i>) was established for a training set of 23 congeneric biologically active azole compounds with known experimental log <i>BB</i> (<i>BB</i> = <i>C</i><sub>blood</sub>/<i>C</i><sub>brain</sub>) values (<i>R</i><sup>2</sup> = 0.9039). The reliability and predictive potency of the model were confirmed by leave-one-out cross validation as well as leave-50%-out cross validation. Multiple linear regression (MLR) was used to develop the quantitative structure-activity relationships (QSARs) to predict the log <i>BB</i> values of compounds that were tested, taking into account the chromatographic lipophilicity (log <i>k<sub>w</sub></i>), polarizability and topological polar surface area. The excellent statistics of the developed MLR equations (<i>R</i><sup>2</sup> > 0.8 for all columns) showed that it is possible to use the HPLC technique and retention data to produce reliable blood-brain barrier permeability models and to predict the log <i>BB</i> values of our pharmaceutically important molecules.https://www.mdpi.com/1420-3049/25/3/487hplcblood-brain barrier permeabilityiam columncholester columnods columnqsarslfers |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Małgorzata Janicka Małgorzata Sztanke Krzysztof Sztanke |
spellingShingle |
Małgorzata Janicka Małgorzata Sztanke Krzysztof Sztanke Predicting the Blood-Brain Barrier Permeability of New Drug-Like Compounds via HPLC with Various Stationary Phases Molecules hplc blood-brain barrier permeability iam column cholester column ods column qsars lfers |
author_facet |
Małgorzata Janicka Małgorzata Sztanke Krzysztof Sztanke |
author_sort |
Małgorzata Janicka |
title |
Predicting the Blood-Brain Barrier Permeability of New Drug-Like Compounds via HPLC with Various Stationary Phases |
title_short |
Predicting the Blood-Brain Barrier Permeability of New Drug-Like Compounds via HPLC with Various Stationary Phases |
title_full |
Predicting the Blood-Brain Barrier Permeability of New Drug-Like Compounds via HPLC with Various Stationary Phases |
title_fullStr |
Predicting the Blood-Brain Barrier Permeability of New Drug-Like Compounds via HPLC with Various Stationary Phases |
title_full_unstemmed |
Predicting the Blood-Brain Barrier Permeability of New Drug-Like Compounds via HPLC with Various Stationary Phases |
title_sort |
predicting the blood-brain barrier permeability of new drug-like compounds via hplc with various stationary phases |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2020-01-01 |
description |
The permeation of the blood-brain barrier is a very important consideration for new drug candidate molecules. In this research, the reversed-phase liquid chromatography with different columns (Purosphere RP-18e, IAM.PC.DD2 and Cosmosil Cholester) was used to predict the penetration of the blood-brain barrier by 65 newly-synthesized drug-like compounds. The linear free energy relationships (LFERs) model (log <i>BB</i> = <i>c</i> + <i>eE</i> + <i>sS</i> + <i>aA</i> + <i>bB</i> + <i>vV</i>) was established for a training set of 23 congeneric biologically active azole compounds with known experimental log <i>BB</i> (<i>BB</i> = <i>C</i><sub>blood</sub>/<i>C</i><sub>brain</sub>) values (<i>R</i><sup>2</sup> = 0.9039). The reliability and predictive potency of the model were confirmed by leave-one-out cross validation as well as leave-50%-out cross validation. Multiple linear regression (MLR) was used to develop the quantitative structure-activity relationships (QSARs) to predict the log <i>BB</i> values of compounds that were tested, taking into account the chromatographic lipophilicity (log <i>k<sub>w</sub></i>), polarizability and topological polar surface area. The excellent statistics of the developed MLR equations (<i>R</i><sup>2</sup> > 0.8 for all columns) showed that it is possible to use the HPLC technique and retention data to produce reliable blood-brain barrier permeability models and to predict the log <i>BB</i> values of our pharmaceutically important molecules. |
topic |
hplc blood-brain barrier permeability iam column cholester column ods column qsars lfers |
url |
https://www.mdpi.com/1420-3049/25/3/487 |
work_keys_str_mv |
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