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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MDPI AG
2022-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/1/34 |
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| author | Monika Kadela-Tomanek Maria Jastrzębska Elwira Chrobak Ewa Bębenek |
| author_facet | Monika Kadela-Tomanek Maria Jastrzębska Elwira Chrobak Ewa Bębenek |
| author_sort | Monika Kadela-Tomanek |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T11:29:00Z |
| format | Article |
| id | doaj.art-f16db82ea71e435d99d4ab63422b6714 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T11:29:00Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-f16db82ea71e435d99d4ab63422b67142023-11-30T23:56:45ZengMDPI AGPharmaceutics1999-49232022-12-011513410.3390/pharmaceutics15010034Lipophilicity and ADMET Analysis of Quinoline-1,4-quinone HybridsMonika Kadela-Tomanek0Maria Jastrzębska1Elwira Chrobak2Ewa Bębenek3Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 4 Jagiellońska Str., 41-200 Sosnowiec, PolandSilesian Center for Education and Interdisciplinary Research, Institute of Physics, University of Silesia, 75 Pułku Piechoty 1a, 41-500 Chorzów, PolandDepartment of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 4 Jagiellońska Str., 41-200 Sosnowiec, PolandDepartment of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 4 Jagiellońska Str., 41-200 Sosnowiec, PolandLipophilicity 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.https://www.mdpi.com/1999-4923/15/1/34lipophilicityquinolineADMETmolecular docking |
| spellingShingle | Monika Kadela-Tomanek Maria Jastrzębska Elwira Chrobak Ewa Bębenek Lipophilicity and ADMET Analysis of Quinoline-1,4-quinone Hybrids Pharmaceutics lipophilicity quinoline ADMET molecular docking |
| 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 | lipophilicity quinoline ADMET molecular docking |
| url | https://www.mdpi.com/1999-4923/15/1/34 |
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