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Lipophilicity and ADMET Analysis of Quinoline-1,4-quinone Hybrids
Lipophilicity is one of the basic properties of a potential drug determining its solubility in non-polar solvents and, consequently, its ability to passively penetrate the cell membrane, as well as the occurrence of various pharmacokinetic processes, including adsorption, distribution, metabolism, e...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9867208/ https://www.ncbi.nlm.nih.gov/pubmed/36678664 http://dx.doi.org/10.3390/pharmaceutics15010034 |
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author | Kadela-Tomanek, Monika Jastrzębska, Maria Chrobak, Elwira Bębenek, Ewa |
author_facet | Kadela-Tomanek, Monika Jastrzębska, Maria Chrobak, Elwira Bębenek, Ewa |
author_sort | Kadela-Tomanek, Monika |
collection | PubMed |
description | Lipophilicity is one of the basic properties of a potential drug determining its solubility in non-polar solvents and, consequently, its ability to passively penetrate the cell membrane, as well as the occurrence of various pharmacokinetic processes, including adsorption, distribution, metabolism, excretion, and toxicity (ADMET). Heterocyclic compounds containing a nitrogen atom play a significant role in the search for new drugs. In this study, lipophilicity as well as other physicochemical, pharmacokinetic and toxicity properties affecting the bioavailability of the quinolone-1,4-quinone hybrids are presented. Lipophilicity was determined experimentally as well as theoretically using various computer programs. The tested compounds showed low values of experimental lipophilicity and its relationship with the type of 1,4-quinone moiety. Introduction of the nitrogen atom reduced the lipophilicity depending on the position at the 5,8-quinolinedione moiety. The bioavailability of the tested compounds was determined in silico using the ADMET parameters. The obtained parameters showed that most of the hybrids can be used orally and do not exhibit neurotoxic effects. Similarity analysis was used to examine the relationship between the ADMET parameters and experimental lipophilicity. The ability of hybrids to interact with biological targets was characterized by global reactivity descriptors. The molecular docking study showed that the hybrids can inhibit the BCL-2 protein. |
format | Online Article Text |
id | pubmed-9867208 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98672082023-01-22 Lipophilicity and ADMET Analysis of Quinoline-1,4-quinone Hybrids Kadela-Tomanek, Monika Jastrzębska, Maria Chrobak, Elwira Bębenek, Ewa Pharmaceutics Article Lipophilicity is one of the basic properties of a potential drug determining its solubility in non-polar solvents and, consequently, its ability to passively penetrate the cell membrane, as well as the occurrence of various pharmacokinetic processes, including adsorption, distribution, metabolism, excretion, and toxicity (ADMET). Heterocyclic compounds containing a nitrogen atom play a significant role in the search for new drugs. In this study, lipophilicity as well as other physicochemical, pharmacokinetic and toxicity properties affecting the bioavailability of the quinolone-1,4-quinone hybrids are presented. Lipophilicity was determined experimentally as well as theoretically using various computer programs. The tested compounds showed low values of experimental lipophilicity and its relationship with the type of 1,4-quinone moiety. Introduction of the nitrogen atom reduced the lipophilicity depending on the position at the 5,8-quinolinedione moiety. The bioavailability of the tested compounds was determined in silico using the ADMET parameters. The obtained parameters showed that most of the hybrids can be used orally and do not exhibit neurotoxic effects. Similarity analysis was used to examine the relationship between the ADMET parameters and experimental lipophilicity. The ability of hybrids to interact with biological targets was characterized by global reactivity descriptors. The molecular docking study showed that the hybrids can inhibit the BCL-2 protein. MDPI 2022-12-22 /pmc/articles/PMC9867208/ /pubmed/36678664 http://dx.doi.org/10.3390/pharmaceutics15010034 Text en © 2022 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 Kadela-Tomanek, Monika Jastrzębska, Maria Chrobak, Elwira Bębenek, Ewa Lipophilicity and ADMET Analysis of Quinoline-1,4-quinone Hybrids |
title | Lipophilicity and ADMET Analysis of Quinoline-1,4-quinone Hybrids |
title_full | Lipophilicity and ADMET Analysis of Quinoline-1,4-quinone Hybrids |
title_fullStr | Lipophilicity and ADMET Analysis of Quinoline-1,4-quinone Hybrids |
title_full_unstemmed | Lipophilicity and ADMET Analysis of Quinoline-1,4-quinone Hybrids |
title_short | Lipophilicity and ADMET Analysis of Quinoline-1,4-quinone Hybrids |
title_sort | lipophilicity and admet analysis of quinoline-1,4-quinone hybrids |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9867208/ https://www.ncbi.nlm.nih.gov/pubmed/36678664 http://dx.doi.org/10.3390/pharmaceutics15010034 |
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