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Lipophilic Studies and In Silico ADME Profiling of Biologically Active 2-Aminothiazol-4(5H)-one Derivatives
Pseudothiohydantoin derivatives have a wide range of biological activities and are widely used in the development of new pharmaceuticals. Lipophilicity is a basic, but very important parameter in the design of potential drugs, as it determines solubility in lipids, nonpolar solvents, and makes it po...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418735/ https://www.ncbi.nlm.nih.gov/pubmed/37569606 http://dx.doi.org/10.3390/ijms241512230 |
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author | Redka, Małgorzata Baumgart, Szymon Kupczyk, Daria Kosmalski, Tomasz Studzińska, Renata |
author_facet | Redka, Małgorzata Baumgart, Szymon Kupczyk, Daria Kosmalski, Tomasz Studzińska, Renata |
author_sort | Redka, Małgorzata |
collection | PubMed |
description | Pseudothiohydantoin derivatives have a wide range of biological activities and are widely used in the development of new pharmaceuticals. Lipophilicity is a basic, but very important parameter in the design of potential drugs, as it determines solubility in lipids, nonpolar solvents, and makes it possible to predict the ADME profile. The aim of this study was to evaluate the lipophilicity of 28 pseudothiohydantoin derivatives showing the inhibition of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) using chromatographic methods. Experimentally, lipophilicity was determined by reverse phase thin layer chromatography (RP-TLC) and reverse phase high-performance liquid chromatography (RP-HPLC). In both methods, methanol was used as the organic modifier of the mobile phase. For each 2-aminothiazol-4(5H)-one derivative, a relationship was observed between the structure of the compound and the values of the lipophilicity parameters (log k(w), R(M0)). Experimental lipophilicity values were compared with computer calculated partition coefficient (logP) values. A total of 27 of the 28 tested compounds had a lipophilicity value < 5, which therefore met the condition of Lipinski’s rule. In addition, the in silico ADME assay showed favorable absorption, distribution, metabolism, and excretion parameters for most of the pseudothiohydantoin derivatives tested. The study of lipophilicity and the ADME analysis indicate that the tested compounds are good potential drug candidates. |
format | Online Article Text |
id | pubmed-10418735 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-104187352023-08-12 Lipophilic Studies and In Silico ADME Profiling of Biologically Active 2-Aminothiazol-4(5H)-one Derivatives Redka, Małgorzata Baumgart, Szymon Kupczyk, Daria Kosmalski, Tomasz Studzińska, Renata Int J Mol Sci Article Pseudothiohydantoin derivatives have a wide range of biological activities and are widely used in the development of new pharmaceuticals. Lipophilicity is a basic, but very important parameter in the design of potential drugs, as it determines solubility in lipids, nonpolar solvents, and makes it possible to predict the ADME profile. The aim of this study was to evaluate the lipophilicity of 28 pseudothiohydantoin derivatives showing the inhibition of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) using chromatographic methods. Experimentally, lipophilicity was determined by reverse phase thin layer chromatography (RP-TLC) and reverse phase high-performance liquid chromatography (RP-HPLC). In both methods, methanol was used as the organic modifier of the mobile phase. For each 2-aminothiazol-4(5H)-one derivative, a relationship was observed between the structure of the compound and the values of the lipophilicity parameters (log k(w), R(M0)). Experimental lipophilicity values were compared with computer calculated partition coefficient (logP) values. A total of 27 of the 28 tested compounds had a lipophilicity value < 5, which therefore met the condition of Lipinski’s rule. In addition, the in silico ADME assay showed favorable absorption, distribution, metabolism, and excretion parameters for most of the pseudothiohydantoin derivatives tested. The study of lipophilicity and the ADME analysis indicate that the tested compounds are good potential drug candidates. MDPI 2023-07-31 /pmc/articles/PMC10418735/ /pubmed/37569606 http://dx.doi.org/10.3390/ijms241512230 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Redka, Małgorzata Baumgart, Szymon Kupczyk, Daria Kosmalski, Tomasz Studzińska, Renata Lipophilic Studies and In Silico ADME Profiling of Biologically Active 2-Aminothiazol-4(5H)-one Derivatives |
title | Lipophilic Studies and In Silico ADME Profiling of Biologically Active 2-Aminothiazol-4(5H)-one Derivatives |
title_full | Lipophilic Studies and In Silico ADME Profiling of Biologically Active 2-Aminothiazol-4(5H)-one Derivatives |
title_fullStr | Lipophilic Studies and In Silico ADME Profiling of Biologically Active 2-Aminothiazol-4(5H)-one Derivatives |
title_full_unstemmed | Lipophilic Studies and In Silico ADME Profiling of Biologically Active 2-Aminothiazol-4(5H)-one Derivatives |
title_short | Lipophilic Studies and In Silico ADME Profiling of Biologically Active 2-Aminothiazol-4(5H)-one Derivatives |
title_sort | lipophilic studies and in silico adme profiling of biologically active 2-aminothiazol-4(5h)-one derivatives |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418735/ https://www.ncbi.nlm.nih.gov/pubmed/37569606 http://dx.doi.org/10.3390/ijms241512230 |
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