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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...

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Autores principales: Kadela-Tomanek, Monika, Jastrzębska, Maria, Chrobak, Elwira, Bębenek, Ewa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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